Beclin-1 expression is upregulated by spermine in rat myocardial ische-mia-reperfusion injury

AIM: To observe the effects of spermine (SP) on myocardial ischemia-reperfusion (IR) injury in rats. METHODS: SD rats (weighing 220~250 g) were equally randomized to 3 groups:sham control group, in which the rats were only treated with thoracotomy; IR group, in which the rats were treated with ischemia for 30 min and reperfusion for 60 min; and IR+SP group, in which 0.5 mmol/L SP (2 mL/kg) was intravenously injected just 15 min before reperfusion. The morphological changes of myocardial tissues were assessed by HE staining. The levels of cardiac troponin I (cTnI) and creatine kinase isoenzyme MB (CK-MB) in plasma were determined. Myocardial infarct size and no-reflow range of the myocardium were measured by Evans blue and thioflavin S staining. Inflammatory responses in the myocardial tissues were detected by myeloperoxidase (MPO) assay. The autophagy function was detected by measuring the protein expression of beclin-1 by Western blot. RESULTS: The myocardial injury and inflammatory infiltration in IR+SP group were reduced under light microscope. Treatment with SP decreased the plasma levels of cTnI and CK-MB, and reduced the IR-induced infarct size and no-reflow range size of the left ventricle (P<0.05). Tissue MPO assay showed that myocardial inflammatory responses were attenuated in IR+SP group compared with IR group. Beclin-1 was upregulated in IR+SP group compared with IR group (P<0.05). CONCLUSION: Exogenous SP attenuates myocardial ischemia-reperfusion injury by upregulating the expression of beclin-1.     

X-ray irradiation increases sensitivity of myocardium to ischemia/reperfusion injury in rats

AIM：To observe the sensitivity of myocardium to ischemia/reperfusion (I/R) injury in the rats with chest radiotherapy. METHODS：The radiation-induced heart disease model was established by local 20 Gy of X-ray irradiation in the chest. Male Wistar rats (n=42) were randomly divided into 6 groups:sham trauma group, trauma group, sham trauma+sham operation group, sham trauma +I/R group, trauma+sham operation group and trauma+I/R group. The rats were subjected to 30 min of ischemia and 1 h of reperfusion 2 week after trauma. The left ventricular developed pressure (LVDP) and ±dp/dtmax were recorded by BL-410 biological signal recording and analysis system. The serum cardiac troponin I (cTnI) and creatine kinase isoenzyme (CK-MB) were measured by ELISA. The myocardial infarct size was determined by nitroblue tetrazolium(NBT) staining method and BI2000 image analysis software. RESULTS：Compared with sham trauma+I/R group, significant decreases in LVDP and ±dp/dtmax were observed in trauma+I/R group (P<0.01) with significant increases in the infarct size and the concentrations of cTnI and CK-MB (P<0.01). CONCLUSION:Chest X-ray irradiation increases the sensitivity of myocardium to I/R injury in rats.     

Changes of heart function and serum cardiac troponin I in early type 2 diabetic rats

AIM: To observe the changes of heart function and the expression of serum cardiac troponin I(cTnI) in early type 2 diabetic rats, and to explore the role of cTnI in the development of type 2 diabetes and early diabetic cardiomyopathy.METHODS: The type 2 diabetes rat model was established by an injection of streptozotocin after high fat diet(5 weeks). The rats were randomly divided into control group, model group of 2 weeks, and model group of 4 weeks. M-mode echocardiography was performed for echocardiographic measurements. Fasting blood glucose(FBG), total cholesterol(TC), triglyceride(TG), high density lipoprotein-cholesterol(HDL-C), low density lipoprotein- cholesterol(LDL-C), fasting insulin(FINS) and cTnI levels were tested. HE staining was used to observe the pathological changes of myocardial structures. The alteration of cTnI in myocardium was determined by Western blot.RESULTS: Compared with normal group, the levels of TC, TG and LDL-C in type 2 diabetic rats were significantly increased, HDL-C levels were significantly reduced. Cardiac histological analysis revealed that type 2 diabetes induced cardiomyocytes degeneration and necrosis. The expression of cTnI increased significantly in diabetic groups compared to control group, and that in model group of 4 weeks increased far more than that in model group of 2 weeks(P<0.05).CONCLUSION: The increased level of cTnI and the change of the heart function may be associated with the development diabetic cardiomyopathy. These changes are valuable for the early clinical diagnosis of myocardial injury in diabetic cardiomyopathy.     

Effects of naringenin on PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways in rats with myocardial ischemia/reperfusion injury

AIM To observe the effect of naringenin on cardiac injury in ischemia/reperfusion （I/R） rats, and to explore whether the role of naringenin is involved in PI3K/AKT signaling pathway and endoplasmic reticulum stress and its related apoptotic pathways. METHODS SD rats （n=48） were randomly divided into sham operation （sham） group, model （I/R） group, naringenin treatment （NAR） group and naringenin+LY294002 （NL） group. Myocardial I/R injury model was prepared by ligation of left anterior descending coronary artery of rats for 30 min followed by reperfusion for 120 min. After reperfusion, the serum levels of cardiac troponin I （cTnI） was measured by ELISA. HE staining, TTC staining and TUNEL staining were used to detect the myocardial histopathological changes, myocardial infarction area and myocardial cell apoptotic rate. The mRNA levels of endoplasmic reticulum stress-related indicators glucose-regulated protein 78 （GRP78）, C/EBP homologous protein （CHOP） and caspase-12 were detected by RT-qPCR. The protein levels of cleaved caspase-3, GRP78, CHOP, caspase-12, p-PI3K and p-AKT were determined by Western blot. RESULTS Compared with I/R group, the serum content of cTnI, myocardial pathological damage, myocardial infarction area and myocardial cell apoptotic rate were significantly reduced （P<0.05）, the protein levels of cleaved caspase-3, GRP78, CHOP and caspase-12 were decreased （P<0.05）, and the protein levels of p-PI3K and p-AKT were increased in NAR group （P<0.05）. LY294002 attenuated the protective effect of naringenin to some extent. CONCLUSION Naringenin reduces myocardial I/R injury in rats possibly by activating PI3K/AKT signaling pathway and subsequently regulating endoplasmic reticulum stress and its related apoptotic pathways.     

Yiqi-Yangyin recipe attenuates myocardial ischemia-reperfusion injury in diabetic rats by activation of ERK/Nrf2/HO-1 pathway

AIM: To explore the effect of Yiqi-Yangyin recipe on myocardial ischemia-reperfusion injury (MIRI) in rats with diabetes mellitus (DM) and the possible mechanism. METHODS: The rats were divided into normal group (control group), DM sham operation (DM-S) group, DM+MIRI group, low-, medium-and high-dose Yiqi-Yang-yin recipe (TL, TM and TH) groups (7.5, 15 and 30 g/kg decoction of Yiqi-Yangyin recipe by gavage), and Nrf2 inhibitor (bardoxolone methyl) group (30 mg/kg bardoxolone methyl by intragastric administration). The gavage volume was 1 mL/kg. There were 15 rats in each group, and they were administered continuously for 7 d. The tail vein blood was collec-ted after the last administration to detect the blood sugar and lipid levels in the rats. The serum levels of cardiac troponin I (cTnI), tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-10 were measured by ELISA. Echocardiography was used to detect the changes of cardiac function in the rats after blood collection. After cardiac function test, the rats were sacrificed to obtain cardiac tissues, and the volume changes of myocardial infarction were assessed by triphenylte-trazole chloride staining. The histopathological changes of myocardium was observed by HE staining. The cardiomyocyte apoptosis was determined by TUNEL assay. The protein levels of phosphorylated extracellular signal-regulated kinase (p-ERK), nuclear factor E2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in the myocardium were determined by Western blot. The myocardial activity of superoxide dismutase (SOD) was measured by nitro blue tetrazolium method, the content of malondialdehyde (MDA) was tested by thiobarbituric acid method, and the production of reactive oxygen species (ROS) was analyzed by iron ion reduction method. RESULTS: Compared with control group, the levels of fasting blood glucose (FBG), total cholesterol (TC) and triglyceride (TG) in DM-S group and DM+MIRI group were significantly elevated, while the level of high-density lipoprotein cholesterol (HDL-C) was significantly lowered (P<0.05). Compared with DM-S group and DM+MIRI group, the levels of FBG, TC, TG in TL, TM, TH and bardoxolone methyl groups were significantly decreased, while HDL-C level was significantly increased (P<0.05). Compared with control group and DM-S group, heart rate (HR) and left ventricular end-diastolic pressure (LVEDP) were increased in DM+MIRI group, mean arterial pressure (MAP), left ventricular systolic pressure (LVSP) and left ventricular ejection fraction (LVEF) were decreased, serum levels of cTnI, TNF-α, IL-1β and IL-10 were increased, the myocardial infarction volume percentage was increased, the myocardial cell breakage and necrosis were increased, the myocardial cell apoptotic rate was increased, the protein levels of p-ERK1/2, Nrf2 and HO-1 were decreased, MDA and ROS levels were increased, and the activity of SOD was decreased (P<0.05). Compared with DM+MIRI group, HR and LVEDP were decreased in TL, TM, TH and bardoxolone methyl groups, MAP, LVSP and LVEF were increased, the serum levels of cTnI, TNF-α, IL-1β and IL-10 were decreased, the myocardial infarction volume percentage was decreased, myocardial cell breakage and necrosis were decreased, myocardial cell apoptotic rate was decreased, the protein levels of p-ERK1/2, Nrf2 and HO-1 were increased, the MDA and ROS levels were decreased, and the activity of SOD was increased (P<0.05). CONCLUSION: Yiqi-Yangyin recipe protects the myocardial tissue of DM+MIRI rats from injury and reduces the oxidative stress level, which may be achieved by activating ERK/Nrf2/HO-1 pathway.     

Effects of tanshinone IIA on cardiac monophasic action potential in acute cerebral ischemia rats

AIM: To investigate the effects of tanshinone IIA (Tan) on cardiac action potential in rats with acute cerebral ischemia (ACI). METHODS: ACI was established in rats accordingly. Animals were divided into 3 groups:sham group, ACI group, and ACI with Tan treatment group. The defect of neural function in each group was graded, electrocardiogram was measured, monophasic action potential was recorded, and the levels of cardiac troponin I (cTnI) and creatine kinase-MB (CK-MB) were examined by commercially available kits. RESULTS: Compared with ACI group, Tan significantly decreased the scores of the defect of neural function, reduced the incidence and duration of the abnormalities in electrocardiogram, prolonged the effective refractory period, action potential duration at 50% repolarization and action potential duration at 90% repolarization, and inhibited the elevation of cTnI and CK-MB levels. CONCLUSION: Tan maintains a stable heart rhythm in ACI rats, which may be related to its protective effect on ischemic myocardium.     

Protection of the limb ischemic preconditioning on the injury of gut is concerned with NO/ET-1 system in rats

AIM: To study the relationship between disturbance of nitric oxide/endothelin-1 (NO/ET-1) and the injury of gut following limb ischemia-reperfusion (I/R) in rats as well as the regulation of NO/ET-1 system by limb I/R preconditioning (IPC). METHODS: A limb ischemia-reperfusion injury model in rats was established. The animals were randomly divided into three groups: control group, IR group and IPC group. The contents of diamide oxidase(DAO), nitric oxide (NO), endothelin-1 (ET-1) and ratio of nitric oxide/endothelin-1 (NO/ET-1) in the plasma and the gut were measured. The leavels of myeloperoxidase, ratio of DNA chain (%), total nitric oxide synthase (tNOS), inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS) in the gut were determined. The expression of iNOS and endothelial NOS (eNOS) were detected by the immunohistochemical method. RESULTS: It was found that the levels of NO, ET-1 in the plasma and the gut tissue all increased after reperfusion, while the values of NO/ ET-1 decreased. The values of DAO in the plasma and MPO in the gut increased, while the contents of DAO and the ratio of DNA chain (%) in the gut decreased. The expression of iNOS elevated, cNOS (mainly eNOS) reduced and total NOS increased. The protection of the limb IPC attenuated the disturbance of NO/ET-1. CONCLUSION: The intestinal injury following limb I/R is related to the disturbance of NO/ET-1. The protection of the limb IPC might be conducted by its regulating NO/ET-1 system. The endothelial NOS increases and non-endothelial NOS decreases in this situation.     

Effects of aminophylline used in the early stage of resuscitation on adenosine and vaso-active factors

AIM: To investigate the effects of aminophylline used early in resuscitation on achievement ratio of resuscitation, the concentrations of plasma norepinephrine (NE), adenosine and nitric oxide (NO), and the levels of cardiac tissue endothelin-1 (ET-1) and adenosine in rats with sudden cardiac arrest. METHODS: Sixty SD rats were randomly divided into three groups: operated control (group A), epinephrine treatment (group B), and epinephrine plus aminophylline treatment (group C). Each group had 20 rats. The concentrations of plasma NE, adenosine and NO, and the levels of cardiac tissue ET-1 and adenosine were examined in group A and 30 min after survived in group B and group C. RESULTS: The duration of circulation recovered in group C was less than that in group B, significantly (P＜0.05). The rate of return of spontaneous circulation and survival to 30 min was achieved in 75% and 70% in group C, while those were achieved in 60% and 55% in group B, respectively (P>0.05). The concentrations of plasma adenosine and NE, and the levels of cardiac tissue ET-1 and adenosine in group B and group C were higher than those in group A significantly (P<0.05). The concentration of NO in group B was also higher than that in group A (P<0.01). The levels of plasma NO and cardiac tissue ET-1 in group C was lower than those in group B significantly (P＜0.05). CONCLUSION: Aminophylline as adenosine receptor antagonist used early in resuscitation not only increases the achievement ratio of resuscitation, but also decreases the levels of ET-1 and NO, so improves after-resuscitation syndrome.     

Protective effect of curcumin on myocardium in diabetic rats

AIM: To study the effects of curcumin (Cur) on diabetic cardiomyopathy (DCM) in rats. METHODS: Male Wistar rats (n=75) were divided into control group and diabetes model group, in which the rats were fed with high-fat diet and then intraperitoneally injected with streptozotocin (STZ, 40 mg/kg). Fasting blood glucose was measured 72 h and 1 week after STZ injection. The diabetic rats were diagnosed when sustained fasting blood glucose levels ≥ 11.6 mmol/L. The diabetic rats were randomly divided into DCM group, DCM+Cur 100 mg/kg group and DCM+Cur 200 mg/kg group. After treatment for 16 weeks, glutathione peroxidase (GSH-Px) activity and malondialdehyde (MDA) level were measured, and the level of cardiac troponin I (cTnI) in the serum was determined by enzyme-linked immunosorbent assay. The protein expression of protein kinase C (PKC) was detected by Western blotting. RESULTS: Curcumin significantly decreased the blood glucose level, increased the body weight, inhibited MDA content and up-regulated the GSH-Px activity in the diabetic rats. Furthermore, curcumin treatment inhibited the diabetes-induced protein expression of PKC. CONCLUSION: Curcumin may have a protective effect on diabetic cardiomyopathy by attenuating oxidative stress.     

The protective effects of angiotensin Ⅱ receptor blocker irbesartan on kidney function in diabetic rats

AIM: To investigate the effects and mechanisms of irbesartan, one of the angiotensin Ⅱreceptor blockers, on kidney function in diabetic rats. METHODS: Forty adult male Wistar rats were randomly divided into four groups: control group, diabetes group, irbesartan group and captopril group. At the end of 12 weeks, the rats were sacrificed. Urine volume, body weight, kidney weight/body weight, plasma, glucose, glycosylated hemoglobin (HbA₁c), urinary β₂-microglobulin (β₂-MG) excretion, urinary albumin excretion rate (UAR), creatinine clearance (Ccr) were measured. Nitric oxide (NO) and endothelin-1 (ET-1) levels in plasma, urinary and renal tissues were determined. RESULTS: Urine volume, kidney weight/body weight, plasma glucose, HbA1C, UAR, Ccr, urinary β₂-MG excretion, NO and ET-1 levels of urinary, blood and renal tissue in diabetic rats were significantly higher than those of normal controls ( P<0.01). UAR, Ccr, urinary β₂-MG excretion, ET-1 and NO levels of urinary and renal tissue in rats of irbesartan and captopril groups were significantly lower than those of DM rats ( P<0.01). There were positive relationships among the levels of plasma, urinary, renal tissue ET-1, NO and UAR, Ccr and urinary β₂-MG excretion. CONCLUSION: Irbesartan could prevent from the injury of renal function in STZ-induced diabetic rats. And it maybe one of the most importan mechanisms that irbesartan could reduce the NO and ET-1 levels in STZ-induced diabetic rats.     

Ischemic postconditioning reduces myocardial damage in rats suffering from limb ischemia-reperfusion

AIM: To investigate the protective effect of limb ischemic postconditioning on the myocardial damage in the rats suffering from limb ischemia-reperfusion (LIR). METHODS: Wistar rats were randomly divided into control group (C group), ischemia-reperfusion group (IR group) and ischemic post-conditioning group (IR+IPostC group). For conducting ischemic postconditioning, the rats in IR+IPostC group underwent 5 min of ischemia and 5 min of reperfusion on their hind limbs repeatedly after 4 h of ischemia, and then, 4 h of reperfusion was applied. The activity of superoxide dismutase (SOD), xanthine oxidase (XOD) and myeloperoxidase (MPO) was measured. The levels of malonaldehyde (MDA) in plasma and myocardial tissues, the levels of creatine kinase (CK), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), α-hydroxybutyrate dehydrogenase (α-HBDH) and myocardial troponin I (cTnI) were also detected. The changes of ultrastructure in the myocardium were observed under electron microscope. RESULTS: Compared with C group,the levels of CK-MB, AST, LDH,α-HBDH and cTnI were all increased in IR and IR+IPostC groups. The levels of MDA and XOD also increased (P<0.05), but the activity of SOD decreased (P<0.05). However, compared with group IR, the levels of CK-MB, AST, LDH, α-HBDH and cTnI decreased (P<0.05) in IR+IPostC group.The levels of MDA and XOD also decreased (P<0.05), but the activity of SOD increased (P<0.05). Under electron microscope, the cardiac myofibrils arranged neatly, light and dark bands were clear, the mitochondrial cristae arranged closely and neatly, and the mitochondrial matrix densification was observed in C group. However, the cardiac fiber arrangement was disordered or disappeared, stromal edema was obvious, most or all mitochondrial cristae and membrane became fusion or disappeared, mitochondrial vacuolization and decrease in glycogen were obvious in IR group. In IR+IPostC group, the pathological changes mentioned above were attenuated somewhat than those in IR group. CONCLUSION: Ischemic postconditioning protects rat myocardium under limb ischemia-reperfusion.     

Establishment and evaluation of rat heart ischemia-reperfusion injury model in vivo

AIM: To establish and evaluate a rat model of heart ischemia-reperfusion injury in vivo. METHODS: Seventy-two male Sprague-Dawley rats weighing(250±50)g were randomly divided into sham operation group(sham), ischemia-reperfusion group(I/R) and normal group. The animals were anesthetized and heparinized. Myocardial ischemia-reperfusion was induced by ligating the left anterior descending coronary artery with "U-shape tube" for 35 min followed by 120 min or 240 min reperfusion in vivo. The heart infarct size was measured by triphenyltetrazolium chloride(TTC) staining. The myocardial cell apoptotic index was determined by the method of terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling(TUNEL). Immunohistochemical method was used to detect the expression of Bcl-2 and Bax in rat ischemia myocardium. The blood level of MB isoenzyme of creatine kinase(CK-MB),cardiac troponin I(cTnI),nitric oxide(NO),malondialdehyde(MDA), total superoxide dismutase(T-SOD)and glutathione peroxidase(GSH-Px) were detected after reperfusion for 2 h and 4 h. RESULTS: Compared with normal group and sham group, there were obvious changes of ST-T segment and Q wave in the electrocardiogram of I/R group. The blood level of CK-MB, cTnI, NO, MDA and GSH-Px in I/R group increased(P<0.05,P<0.01) after reperfusion for 2 h and 4 h, and the blood level of T-SOD in I/R group after reperfusion for 2 h and 4 h also increased(P<0.05). The heart infarct size in I/R group was the largest as compared to other groups. Among these groups, the apoptotic index of I/R group was the highest and the Bcl-2/Bax ratio in I/R group decreased(P<0.01).CONCLUSION: The rat model of heart ischemia-reperfusion injury in vivo can be successfully established with the "U-shape tube". There are obviously changes of heart infarct size, blood level of CK-MB, cTnI, NO, MDA, T-SOD and GSH-Px, myocardial apoptotic index and Bcl-2/Bax ratio between I/R rats and control animals.     

Stress induced expression of the angiotensinogen gene in rat anterior pituitary

AIM:To observe the effects of sodium restricted or supplemented on atrial natriuretic polypeptide (ANP) and cardiac function of rats with congestive heart failure (CHF).METHODS:CHF rats were divided into three groups with sham operation rats group as control. Radioimmunassay was used to determine the ANP contents of plasma and myocardium, at the same time cardiac function was measured. RESULTS:In sodium restricted group, the plasma sodium and atrial ANP and left ventricular systolic pressure and artery pressure were obviously lower than those in CHF group, while the plasma and ventricular ANP and the right atrial pressure were remarkably higher; In sodium supplemented group, the plasma sodium and arterial pressure had no obvious change compared with the control, the plasma and myocardium ANP and the right atrial pressure had no difference as compared with CHF group, while the left ventricular end diastolic pressure was remarkably lower and the left ventricular systolic pressure were obviously higher. CONCLUSION:Keeping the balance of plasma sodium by an appropriate supplement of sodium intake after CHF might be beneficial to the ANP biological effects and the cardiac function.     

Role of polyamines in L-arginine inhibiting isoproterenol induced cardiac hypertrophy rat

AIM: To explore the role and possible mechanism of polyamine in L-arginine inhibiting cardiac hypertrophy induced by isoproterenol (ISO). METHODS: Hypertrophic model of rats was established using ISO. Pretreated with L-arginine, hypertrophy status of rats was determined by hypertrophy coefficient, collagen content and the expression of ANP mRNA. High performance liquid chromatography (HPLC) was used to measure the concentrations of polyamines. Western blotting was performed to detect the expressions of ornithine decarboxylase (ODC) and spermidine/spermine N1-acetyltransferase (SSAT). The activity and levels of NOS and NO in serum were also observed. RESULTS: Hypertrophy coefficient and expression of ANP mRNA increased significantly after injection of ISO for 7 d. Moreover, cardiac muscle fibres became thick and disorganized. Pretreated with L-arginine, the above index decreased. Meanwhile, the concentration of polyamine was decreased and plasma NO content and NOS activity were increased, the expression of ODC was downregulated and the expression of SSAT was upregulated. CONCLUSION: Exogenous L-arginine inhibits cardiac hypertrophy through downregulating L-arginine/polyamine pathway and upregulating L-arginine/NO pathway.     

Short-term cardioprotective effects of trimetazidine on acute myocardial infarction in rats

AIM: To observe the myocardial protective effects of trimetazidine on myocardial infarction (MI) in Sprague-Dawley (SD) rats. METHODS: Ninety SD rats were randomly assigned to 3 groups (n=30 each): myocardial infarction group (MI group), MI+trimetazidine group (MT group) and sham group (S group). By permanently ligating the left anterior descending artery, the MI model was set up in the rats in MI group and MT group. Before and after setting up the MI model, normal saline was given to the rats in MI and S group by gavage. On the other hand, trimetazidine (3 mg/kg,twice per day) was given to the rats in MT group by gavage. At 8 h, 24 h and 48 h after applying trimetazidine, the serum level of cardiac troponin I (cTnI) was measured. At the 1st week, 2nd week and 4th week after treated with trimetazidine, the size of myocardial infarction, the maximum rising rate of the left ventricular systolic pressure (+dp/dt_max) and the maximum descending rate of the left ventricular diastolic pressure (-dp/dt_max) were measured. Also at the 1st week after applying trimetazidine, the cardiomyocyte apoptotic index was detected. RESULTS: Compared with MI group 2 weeks after applying trimetazidine, +dp/dt_max significantly increased in MT group , and -dp/dt_max also significantly increased in MT group . Four weeks after applying trimetazidine, +dp/dt_max significantly increased in MT group , and -dp/dt_max also significantly increased in MT group . At 8 h and 48 h after applying trimetazidine, no statistically significant difference (P＞0.05) of serum cTnI between MI group and MT group was observed. However, at 24 h after applying trimetazidine, the serum level of cTnI decreased in MT group as compared with MI group . Aditionally, trimetazidine significantly decreased the infarction size of myocardium in MT group (0.248±0.052) as compared with MI group (0.362±0.082, P<0.01). CONCLUSION: Trimetazidine has short-term cardioprotective effects on the rats with acute MI by improving myocardial systolic and diastolic functions, reducing infarct size and inhibiting apoptosis.     

Effects of ligustrazine ferulate on myocardial apoptosis and apoptosis-related protein expression in rats with myocardial ischemia-reperfusion injury

AIM:To observe the effects of ligustrazine ferulate on the apoptosis of myocardial cells in rats with myocardial ischemia-reperfusion injury, and to explore its possible mechanism. METHODS:Sixty male SD rats were randomly divided into five groups: sham-operation group, ischemia-reperfusion group, ligustrazine (4 mg/kg) group, low-dose (4 mg/kg) ligustrazine ferulate group and high-dose (8 mg/kg) ligustrazine ferulate group. The rat myocardial ischemia-reperfusion model was established by 30 min of myocardial ischemia followed by 120 min of reperfusion. Drugs were administered to the rats by jugular vein injection 10 min before reperfusion. After the reperfusion was finished, the biochemical indicators in serum and the histological indexes in myocardium were detected. RESULTS: Compared with ischemia-reperfusion group, ligustrazine ferulate lowered the serum levels of creatine kinase MB form, lactate dehydrogenase, cardiac troponin I and malondialdehyde, elevated the activity of total superoxide dismutase in serum and the expression of Bcl-2 protein in myocardium, decreased the expression of Bax protein and myocardial apoptotic index, and increased the Bcl-2/Bax ratio (all P<0.01). All the indicators in ligustrazine ferulate groups were dose-dependently superior to those in ligustrazine group (P<0.05 or P<0.01). CONCLUSION: Ligustrazine ferulate protects rats against myocardial ischemia-reperfusion injury. Its anti-apoptotic effect may be related to up-regulation of Bcl-2 and down-regulation of Bax.     

The protection of the hepatic ischemic preconditioning is concerned with the NO/ET-1 system

AIM: To study the relationship between the disturbance of nitric oxide/endothelin-1(NO/ET-1) and hepatic ischemia/reperfusion(I/R) injury as well as the regulation of NO/ET-1 system by hepatic ischemic preconditioning(IPC). METHODS: The changes of NO/ET-1 system and their relationship with hepatic I/R injury were compared between I/R group and IPC+I/R group in a rat hepatic I/R model. Two hours after reperfusion, the liver tissues were detected by RT-PCR to see whether there was inducible nitric oxide synthase (iNOS) mRNA expression. RESULTS:In the acute phase of hepatic reperfusion, the ratio of NO/ET-1 was reduced, which was due to a significant reduction of NO₂^-/NO₃^- (the metabolic product of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and of MDA in liver tissue were increased but ATP in liver tissue was reduced, the hepatic damage was deteriorated. The protection of the hepatic IPC was concerned with the elevation of the ratio of NO/ET-1 caused by the elevation of NO₂^-/NO₃^-, and reduction of ET-1 as well. There was no iNOS mRNA detected in the liver tissues.CONCLUSION: Hepatic I/R injury is related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be conducted by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this situation.     

Effect of N-acetyl-L-cystein on blood pressure and endothelial function in aorta of rats exposed to chronic intermittent hypoxia

AIM: To investigate the effect of N-acetyl-L-cystein (NAC) on blood pressure and endothelial function in the aorta of the rats exposed to chronic intermittent hypoxia (CIH). METHODS: Thirty healthy male SD rats were randomly divided into 3 groups: control group, CIH group and CIH+NAC group. The systolic blood pressure (SBP) was measured with tail-cuff me-thod. Real-time fluorescence quantitative polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of endothelial nitric oxide synthase (eNOS） and endothelin-1 (ET-1) in the thoracic aorta. The protein expression of eNOS in the thoracic aorta was examined by Western blotting. The levels of ET-1 in the thoracic aorta and serum were detected by radioimmunoassay. The serum nitric oxide was determined by nitric acid reduction method.The superoxide dismutase (SOD) activity in peripheral blood plasma was detected by xanthine oxidase method.The serum malondialdehyde content was detected by thiobarbituric acid method, and superoxide anion (O-·2) in thoracic aorta was determined by chemical colorimetric method. RESULTS: Compared with the control animals, CIH exposure was associated with decreased SOD level, and NAC-treated CIH animals showed recovery in SOD level. NAC treatment prevented CIH-induced hypertension as well as CIH-induced increase in MDA. The aorta eNOS mRNA and protein, and serum NO levels in CIH group were lower than those in control group, and those in NAC treatment group were higher than those in CIH group. The increases in ET-1 mRNA,ET-1 protein and O-·2 levels in the aorta, and the elevated circulating ET-1 level were also observed in CIH-exposed animals. Treatment with NAC significantly decreased the mRNA and protein levels of ET-1, the O-·2 content, and the circulating ET-1 level in CIH-exposed animals. CONCLUSION: NAC protects endothelial function and alleviates hypertension by suppressing the oxidant stress in the aorta tissues, indicating that oxidant stress may be involved in the mechanism of endothelial disorder of CIH-induced hypertension.     

Plasma levels of endothelin-1, nitric oxide,malondialdehyde and superoxide dismutase in rats exposed to infrasound

AIM: To observe the changes of NO, ET-1, SOD and MDA levels in plasma of rats exposed to infrasound. METHODS: Using infrasound (frequency: 8 Hz; sound pressure level:130 dB), the rats were exposed for 1 d， 7 d， 14 d， 21 d and 28 d, 2 h daily, then the levels of NO, ET-1, SOD and MDA were measured after exposure. RESULTS: The changes of NO levels in plasma significantly declined at 7 d and 14 d （P<0.01）, then 1, 21 and 28 d normally （P>0.05）. The changes of ET-1 levels in all groups in plasma were significantly increased （P<0.01）, mostly at 7 d, least at 14 d. The changes of SOD activity in all groups in plasma were significantly declined （P<0.01）. The changes of MDA levels in all groups in plasma were significantly increased （P<0.01）. CONCLUSIONS: Infrasouns induces changes of NO, ET-1, SOD and MDA in rat plasma, and it depends on infrasound exposure time.