Effects of pretreatment with captopril on the infarct size and myocardial cell apoptosis in experimental rabbits

AIM:To investigate the effects of pretreatment of captopril on the infarct size and myocardial cell apoptosis in rabbits. METHODS:Rabbits were randomly divided into sham-operated control group (SO), acute infarct group (AI) and captopril pretreatment group (CP). The rabbits of CP group were treated with captopril (25 mg·kg^-1.d^-1) for 1 week before harvest. The left circumflex branch of coronary (LCX) was ligated to develop acute ischemic model. The systolic and diastolic function of left ventricle(LV) was measured before and at 15, 30, 60 min after ligating LCX, and the blood viscosity and hematocrit before and at 60 min after ligating LCX were measured also. 6 hours later LCX ligation, the hearts were harvested for determining the infarction size, which was expressed as the ratio of infarct area to the total ischemic area, and evaluating apoptosis index expressed as the percentage of myocardial cells with TUNEL positive staining. RESULTS:1.Compared with AI group, captopril pretreatment significantly reduced the infarction size (16.60%±0.94% vs 36.24%±1.94%, P＜0.05), and improved the LV function and viscosity of blood. 2. Apoptosis of myocardial cell was found in the myocardium surrounding to the infarction area, however, the apoptosis index of CP group was significantly lower than that of AI group (26.30%±0.71% vs 42.44%±2.32%,P＜0.05).CONCLUSION:Apoptosis of myocardial cell exists in the area surrounding the infarction. Captopril pretreatment can reduce infarction size and myocardial apoptosis index, and improve the LV function as well as blood viscosity in this acute ischemic model.     

Effects of Tongxinluo on connexin 43 remodeling and ventricular arrhythmia after myocardial infarction in rats

AIM: To determine the effects of Tongxinluo(TXL) on connexin 43(Cx43) remodeling and ventricular arrhythmia(VA) after myocardial infarction(MI) in rats. METHODS: Male SD rats were randomly divided into sham-operated(sham) group(n=25) and operation group(n=75). The left anterior descending(LAD) was ligated in operated group, while the rats in sham group only underwent pericardiotomy. The rats in operation group which survived for 3 d after operation were randomly assigned to TXL group and MI group. The rats in TXL group was administrated with TXL(2 g·kg^-1·d^-1, intragastric administration) for 4 weeks, while normal saline was applied to the rats in sham group and MI group. The levels of interleukin-1β(IL-1β) and endothelin-1(ET-1) in the tissue from the border zone were measured by ELISA after treatment. The distribution and the mRNA and protein expression of Cx43 were detected by immunohistochemical staining, RT-PCR and Western blotting, respectively. The burst pacing was used to induce ventricular arrhythmia(VA). RESULTS: Compared with sham group, the levels of IL-1β and ET-1 and the incidence of VA were significantly increased, while the mRNA and protein expression of Cx43 was markedly reduced with irregular distribution in MI group(P<0.05). Compared with MI group, the levels of IL-1β and ET-1 and the incidence of VA were significantly reduced, while the expression of Cx43 at mRNA and protein levels was markedly increased with augmented linear distribution in the myocardial cell intercalated disc in TXL group(P<0.05). CONCLUSION: TXL reduces the incidence of VA after MI via inhibiting the Cx43 remodeling.     

Agkistrodon halys venom PCA improves hemorheology in rats with coronary artery microthrombosis

AIM: To explore the effect of protein C activator (PCA) from Wannan Agkistrodon halys venom on hemorheology in the rats with coronary artery microthrombosis(CAM). METHODS: Fifty SD rats were randomly divided into sham operation group, CAM group, low dose (0.5 mg/kg), medium dose (2 mg/kg ) and high dose (8 mg/kg) of PCA treatment groups. The model of CAM was induced by injecting sodium laurate at dose of 1.0 mg/kg with the concentration of 10 g/L from aortic root to left ventricle. Thrombelastogram was obtained by thromboelastography instrument system. The content of endothelin-1(ET-1) and P-selectin, and the activity of creatine kinase-MB (CK-MB),lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) in plasma were determined by ELISA. The protein expression of myocardial P-selectin and TNF-α was detected by Western blotting. The structural changes of the myocardial cells and interstitial tissues were observed under microscope. RESULTS: Compared with CAM group, clotting time and clot formation time significantly prolonged in high-dose PCA group. The alpha angle, maximum amplitude, coagulation index, and the levels of ET-1, P-selectin, CK-MB, LDH and AST in plasma were decreased. The protein expression levels of P-selectin and TNF-α in myocardial tissues were down-regulated (P<0.05). Cardiac histological observation showed that coronary microthrombi in medium-dose and high-dose PCA groups were not found. CONCLUSION: Agkistrodon halys venom PCA inhibits the formation of coronary microthrombi, down-regulates the expression of P-selectin and TNF-α, improves the abnormal hemorheology after microthrombi, and effectively protects myocardial cells.     

Effect of bFGF on promoting angiogenesis in infarct area and improving myocardial fibrosis in mouse myocardial infarction model

AIM: To investigate the protective effect of basic fibroblast growth factor (bFGF) on the heart of mice with myocardial infarction and its mechanism. METHODS: The model of myocardial infarction was established by the ligation of left anterior descending artery of C57/B6 mice (8~12 weeks old) after lateral thoracotomy. The mice were divided into sham operation group, myocardial infarction group and bFGF administration group. bFGF at 0.5 μg was intraperitoneally injected on alternate days after myocardial infarction for 7 d. Cardiac Doppler ultrasonography was used to detect cardiac function after myocardial infarction for 28 d, and left ventricular end-diastolic diameter, left ventricular end-systolic diameter, left ventricular ejection fraction and left ventricular shortening fraction (LVFS) were used to evaluate cardiac function. After myocardial infarction for 28 d, the mice were sacrificed and the hearts were collected for preparing pathological sections. The degrees of myocardial fibrosis and angiogenesis in the myocardial infarction area were observed. Western blot was used to detect the indicators of angiogenesis. RESULTS: The results of Masson staining showed that bFGF administration significantly reduced myocardial fibrosis at 28 d after myocardial infarction. Cardiac ultrasound data showed that cardiac functions in myocardial infarction group were poorer than those in sham group, and bFGF administration significantly improved cardiac functions. Immunofluorescence staining showed that neovascularization in myocardial infarction area of bFGF administration group was more than that in myocardial infarction group. The results of Western blot showed that bFGF activated AKT/HIF-1α/VEGF signaling pathway. CONCLUSION: Intraperitoneal injection of bFGF reduces myocardial fibrosis and improves cardiac function in myocardial infarction mice. bFGF may promote angiogenesis by activating AKT/HIF-1α/VEGF signaling pathway.     

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.     

Effects of noninvasive delayed limb ischemic preconditioning on prognosis of myocardial infarction

AIM: To study the effects of noninvasive delayed limb ischemia preconditioning (NDLIP) on animal cardiac function, myocardial morphology and myocardial apoptosis after myocardial infarction (MI). METHODS: Healthy SD male rats[n=45, weighing (250±10) g] were randomly divided into 3 groups:MI group:the animal model of MI was established by surgical ligation of left anterior descending artery (LAD) after 2 weeks; NDLIP group:after the success of the MI animal model, NDLIP was carried out every other day until the 4th, 6th and 8th weeks; sham group:as the negative control group, the animals were taken heart LAD threading but no ligation. All rats were fed conventionally. At the end of the 4th, 6th and 8th weeks, all rats were made ventricular intubation, and then the hemodynamic parameters were recorded. The blood samples were withdrawn from the abdominal aorta and the serum was separated via centrifugation. The serum contents of Bcl-2 and Bax were measured by ELISA. Left ventricular anterior wall was homogenized. The mitochondrial respiratory chain complexes Ⅰ, Ⅱ, Ⅲ and Ⅳ in the myocardial tissues were detected by ELISA. RESULTS: At the end of the 4th, 6th and 8th weeks, compared with MI group, left ventricular systolic pressure in NDLIP group was significantly increased, while left ventricular end-diastolic pressure in NDLIP group was significantly decreased (both P<0.05). Mitochondrial respiratory chain complexesⅠ, Ⅱ, Ⅲ and Ⅳ in NDLIP group were significantly increased (P<0.05). The serum level of Bcl-2 in NDLIP group was significantly increased and Bax level was reduced remarkably (both P<0.01). CONCLUSION: NDLIP improves the hemodynamic indexes, promotes the mitochondrial respiratory function and inhibits cell apoptosis, thus improving the prognosis of MI.     

Effect of atorvastatin on cardiac function and HGF/c-Met signaling pathway after acute myocardial infarction in diabetic rats

AIM: To investigate the effect of atorvastatin on myocardial apoptosis, ventricular remodeling and cardiac function after acute myocardial infarction (AMI) in diabetic rats, and to explore whether the effect is mediated by hepatocyte growth factor (HGF)/c-Met signaling pathway. METHODS: Diabetes in 70 male SD rats was induced by intraperitoneal injection of streptozotocin (STZ, 65 mg/kg). After 8 weeks, AMI was induced by the ligation of the left anterior descending coronary artery in the diabetic rats, and 32 surviving rats were divided into AMI group (n=16) and AMI＋atorvastatin group (n=16, 20 mg·kg-1·d-1) at random. The similar surgical procedure was completed in sham group (n=11) without coronary ligation. Atorvastatin was given daily by gavage from the first day after AMI. Two weeks later, the cardiac function, pathological changes of myocardial tissues, myocardial apoptosis, and the expression of HGF and c-Met were compared among groups. RESULTS: AMI significantly reduced cardiac function, increased collagen volume fraction (CVF) and myocardial apoptotic index, and up-regulated the expression of HGF and c-Met at mRNA and protein levels in AMI control group (P<0.05). The cardiac function was improved, and CVF and myocardial apoptotic index were reduced by the treatment with atorvastatin, which also up-regulated the expression of HGF and c-Met (P<0.05). CONCLUSION: Atorvastatin significantly attenuates myocardial apoptosis and cardiac remodeling, and improves cardiac function after AMI in diabetic rats by further enhancing the activation of HGF/c-Met pathway.     

Protective effect of heat-shock pretreatment on rat ischemia-reperfusion myocardium

AIM:To investigate the changes of expression of P-selectin (Ps) in ischemia-reperfusion myocardium and to observe the effects of heat shock protein (HSP) on the expression of Ps and apoptosis. METHODS:Mature female Wistar rats (n=40) were divided into three groups at random. Under general anesthesia, the rats in heat-shock group were subjected to whole-body hyperthermia, and those in the other two groups were treated with anesthetic alone. Twenty-four hours later, the animals in heat-shock group and in control group were subjected to surgical operative ligation of coronary left anterior descending branch (LAD) for 1 h, then accepted reperfusion for 2 h. Those in sham operation group were also performed surgical operation without LAD ligation for 3 h. After operation, the CK-MB in blood serum, infarct size of left ventricles, HSP70, Bax, Bcl-2, Ps and apoptosis cells were measured. RESULTS:The amount of HSP70 in heat-shock group was significant higher than that in control group and in sham operation group (P<0.05). There was no difference between control group and sham operation group (P>0.05). Compared with control group, the infarct size, CK-MB, apoptosis cells, Bax and Ps in heat-shock group were significantly reduced (P<0.05). However, expression of Bcl-2 was similar (P>0.05). No expression of Ps in sham operation group was detected. CONCLUSIONS:HSP70 may reduce myocardial apoptosis during ischemia-reperfusion. One of the mechanisms is that HSP70 restraines the expression of Bax and Bax/Bcl-2. Ps plays an injurious role in ischemia-reperfusion myocardium. HSP70 is likely to restrain Ps from expression, which may be one of the mechanisms by which heat-shock pretreatment plays a protective role in ischemia- reperfusion myocardium.     

Effect of galectin-3 on ventricular remodeling in rabbits with ischemic cardiac insufficiency

AIM:To investigate the relationship between galectin-3(Gal-3) and myocardial fibrosis,and to clarify the role of Gal-3 in ventricular remodeling in rabbits with ischemic cardiac insufficiency.METHODS:A rabbit model of ischemic cardiac insufficiency was established by ligation of the anterior descending branch of the coronary artery.The 20 rabbits were randomly divided into sham operation group and cardiac insufficiency group by random number table method.After 4 weeks of coronary artery ligation,the cardiac function was measured by cardiac echocardiogram.Real-time PCR and Western blot were used to detect the expression of Gal-3,type I collagen and type Ⅲ collagen at mRNA and protein levels in the myocardium.The serum Gal-3 contents were measured by ELISA.HE staining and Masson staining were used to observe the degree of fibrosis development in myocardial tissues after infarction.RESULTS:Compared with sham operation group,the mRNA expression of Gal-3 in cardiac insufficiency group was significantly increased.At the same time,type I collagen,type Ⅲ collagen and collagen type I/Ⅲ ratio were also increased significantly.The protein contents of Gal-3,type I collagen and type Ⅲ collagen were increased significantly.The serum Gal-3 levels were significantly increased.The pathological changes were observed in cardiac insufficiency group as the myocardial cell morphological disorder and marked hyperplasia of fibrous tissue were seen.CONCLUSION:Gal-3 aggravates myocardial fibrosis in rabbits with ischemic cardiac insufficiency,and promotes the ventricular remodeling and the occurrence of heart failure.     

Prostaglandin E1 protects heart after myocardial infarction by inhibiting endoplasmic reticulum stress in rats

AIM To investigate the effect of prostaglandin E1 (PGE1) on heart after myocardial infarction (MI) in rats and its related molecular mechanism. METHODS Fifty male SD rats were divided into sham group, model group and model+PGE1 group. The MI rat model was established by ligation of left anterior descending coronary artery. Cardiac function in the rats was detected by echocardiogaphy. The myocardial histomorphologic changes were evaluated by HE and Masson staining. The MI area was measured by TTC staining. The cardiomyocyte death was detected by TUNEL staining. The protein levels of endoplasmic reticulum stress (ERS)-related factors glucose-regulated protein 78 (GRP78), C/EBP homologous protein (CHOP) and caspase-12, and apoptosis-related factors Bcl-2, Bax and cleaved caspase-3 were determined by immunofluorescence staining and Western blot. RESULTS Compared with sham group, the cardiac function in model group was decreased, with significant myocardial pathological changes. The MI area was enlarged, and the death of cardiomyocytes was promoted. The protein levels of GRP78, CHOP, caspase-12, Bax and cleaved caspase-3 in the myocardial tissues were significantly increased, while Bcl-2 was decreased (P<0.01). Compared with model group, the cardiac function in model+PGE1 group was significantly improved, and the myocardial pathological damage was significantlty attenuated. The MI area and myocardial cell death were significantly reduced. The protein levels of GRP78, CHOP, caspase-12, Bax and cleaved caspase-3 in the myocardial tissues were significantly decreased, while Bcl-2 was increased (P<0.01). CONCLUSION PGE1 reduces collagen deposition and inflammation, and improves cardiac function by reducing ERS level, thus protecting cardiomyocytes from MI damage.     

Transplantation of bcl-2 gene-modified bone marrow mesenchymal stem cells improves cardiac function and angiogenesis in rabbit ischemic car-diac insufficiency model

AIM: To investigate the effects of transplantation of bone marrow mesenchymal stem cells (BMSCs) modified by bcl-2 gene on myocardial cell apoptosis, angiogenesis and cardiac function in the rabbit after acute myocardial infarction (MI).METHODS: The rabbit BMSCs were isolated, cultured and purified in vitro. The BMSCs were transfected with adenovirus or adenovirus-Bcl-2. The rabbit model of MI was established by ligation of left anterior descending branch. The rabbits were injected with Ad-Bcl-2-BMSCs (MI+Bcl-2-BMSCs group), Ad-BMSCs (MI+BMSCs group) and DMEM (MI group) in infarction marginal zone 2 weeks after ligation. The cardiac function was evaluated by echocardiography.The apoptosis of myocardial cells was measured by TUNEL. The mRNA expression of VEGF was detected by real-time PCR. The expression of CD31 was examined by immunohistochemical staining, and new blood capillaries were counted at 4 weeks after BMSCs transplantation. The correlation of the above values with cardiac function was analyzed.RESULTS: The cardiac function was better, the apoptotic rate was lower, the mRNA expression of VEGF and the capillary density were higher in both MI+Bcl-2-BMSCs group and the MI+BMSCs group than those in MI group, and those in MI+Bcl-2-BMSCs group increased more obviously.The left ventricular ejection fraction (LVEF) had a negative correlation with the myocardial cell apoptosis rate. A positive correlation with the mRNA expression level of VEGF and the capillary density was also observed.CONCLUSION: The transplantation of BMSCs modified by bcl-2 gene significantly reduces the myocardial cell apoptosis, promotes angiogenesis, improves heart function of the rabbits with MI.     

Effects of atorvastatin on nitric oxide,endothelin-1 and myocardial function in a rabbit model of acute myocardial infarction and reperfusion

AIM: To evaluate the effects of atorvastatin on nitric oxide(NO), endothelin-1(ET-1)and myocardial no-reflow in a rabbit model of acute myocardial infarction and reperfusion(AMI/R). METHODS: Twenty-four rabbits were randomized into 3 groups: 8 in AMI/R group, 8 in atorvastatin-treated group(5 mg·kg-1·d-1)and 8 in sham-operated group. Animals in the former two groups were subjected to 60 min of coronary occlusion followed by 120 min of reperfusion. Data on haemodynamics were collected. NO in blood sample, and in normal, and in infarcted reflow and no-reflow myocardium were evaluated respectively by nitrate reductase method. The levels of ET-1 in blood sample, and in normal, infarcted reflow and no-reflow myocardium were determined by radioimmunoassay. RESULTS: (1)Compared to the baselines, the heart rate(HR), systolic blood pressure(SBP), diastolic blood pressure(DBP), left ventricular systolic pressure(LVSP), maximal rate of increase and decline in left ventricular pressure(±dp/dtmax)and cardiac output(CO)in AMI/R and atorvastatin-treated groups were significantly declined, whereas left ventricular end-diastolic pressure(LVEDP)was increased after 60 min of coronary occlusion and 120 min of reperfusion(P<0.05 or P<0.01). However, in atorvastatin-treated group, LVSP, LVEDP, ±dp/dtmax and CO at the time point of 120 min of reperfusion recovered more significantly than those at the time point of 60 min of coronary occlusion(P<0.01), which was more significant than those in AMI/R group(P<0.05 or P<0.01). Compared to AMI/R group, the SBP and DBP were significantly heigher in atorvastatin-treated group(P<0.01).(2)In atorvastatin-treated group, the levels of ET-1 in blood sample were significantly lower than those in AMI/R group(P<0.01), and the levels of NO were significantly higher(P<0.01). Moreover, the levels of NO or ET-1 in infarcted reflow myocardium were significantly lower than that in AMI/R group(P<0.05 or P<0.01).(3)Atorvastatin could ameliorate myocardial function. CONCLUSION: Atorvastatin is effective in increasing NO and reducing ET-1 in blood plasma and local myocardium, and in protection of endothelial cells. Atorvastatin also has a beneficial effect on improving left ventricular function during acute myocardial infarction and reperfusion in rabbits.     

早熟大粒无核葡萄新品种‘超级无核’

 ‘超级无核’葡萄系从美国引进葡萄新品种‘Superior Seedless’优选单株培育出的优良品种。无核、大粒、早熟、优质、早实、丰产、生长势强健、耐病、耐不利栽培条件, 是适合高温、高湿、少日照地区栽培的无核葡萄新品种。     

Effect of Shenshuguanxin granula on coronary circulation in rats with myocardial infarction

AIM：To explore the effect of traditional Chinese medicine Shenshuguanxin granula on coronary circulation in a rat model of myocardial infarction (MI). METHODS：SD rats (n=50, SPF grade) were randomly divided into 5 groups (n=10):sham group, MI group, and high-dose, middle-dose and low-dose Shenshuguanxin granula treatment groups. The rat MI model was established by ligation of the coronary artery. The cardiac markers, small and medium-sized blood vessels ［microvessel count (MVC) value］ in the infarct zone, and platelet endothelial cell adhesion mo-lecule 1 (PECAM-1) and vascular endothelial growth factor (VEGF) expression in the infarct border zone were measured. RESULTS：After 4 weeks of coronary artery ligation, the significant increases in MVC in the infarct zone, and the expression of PECAM-1 and VEGF in the infarct border zone were detected compared with sham group (P<0.05). The differences of cardiac markers between MI group and other groups were insignificant (P>0.05). CONCLUSION:Shenshuguanxin granula improves coronary circulation in the rats with myocardial infarction by increasing the expression of PECAM-1 and VEGF, and promoting small and medium-sized angiogenesis.     

Cardiomyocyte apoptosis and expression of Bcl-2, Bax protein after acute myocardial infarction and late reperfusion in dogs

AIM: To study the effect of late reperfusion on apoptotic cardiomyocytes in the risk area of acute myocardial infarctin in dogs. METHODS: The experiment was divided into three groups: sham operation group, acute myocardial infarction (AMI) group, and late reperfusion (LR) group. Apart from sham operation group, the other two groups were subjected to left anterior descending branch of coronary artery ligation. The acute myocardial infarction group was only subjected to ligation for 12 hours, late reperfusion group was subjected to ligation for 6 hours following by 6 hours of reperfusion. The cardiomyocyte apoptosis was measured by TUNEL assay. Immunohistochemistry and Western blotting analysis were used to detect the expression of Bcl-2 and Bax protein. RESULTS: The number of apoptotic cardiomyocytes in late reperfusion group was much less than acute myocardial infarction group (P<0.05), and increased significantily as compared with sham operation group (P<0.01). The expression of Bcl-2 protein was enhanced gently in late reperfusion group in contrast to acute myocardial infarction group, but no significant difference in the two groups (P>0.05) was observed, although it was much more in the two groups than that in sham operation group (P<0.01). The expression of Bax protein in late reperfusion group was much higher than that in sham operation group (P<0.01), and was lower than that in acute myocardial infarction group (P<0.05). CONCLUSION: Late reperfusion reduces cardiomyocyte apoptosis in the risk area of acute myocardial infarction. The mechanism may be that late reperfusion can decrease the expression of Bax protein.     

Effect of transmyocardial laser revascularization on myocardial lactatic metabolism and mitochondria of myocardial cells

AIM: We studied the therapeutic effect and mechanism of transmyocardial laser revascularization (TMLR) for the acute myocardial ischemia (AMI). METHODS: 18 dogs were divided randomly and evenly into the control group, the AMI group and the TMLR group. A continuous wave Nd: YAG laser was used for TMLR. Concentration of lactate in artery and coronary sinus (A.Lat and CS.Lat), myocardial metabolic rate of lactate acid (MLR) and myocardial lactate extraction (MLE) were measured before the left anterior descending coronary artery (LAD) ligation and 60 min after the LAD ligation. Myocardial biopsy was made 4 h after the LAD ligation to quantitatively observe the shape and number of mitochondria in myocardial cells by a electric microscope. RESULTS: 60 min after the LAD ligation, CS.Lat were (7.63±4.27) mmol/L in the AMI and (5.78±3.98) mmol/L in the TMLR, respectively (P<0.05); MLR were (0.03±0.01) mmol·100 g^-1 myocardium·min^-1 in the AMI and (0.06±0.02) mmol·100 g^-1 myocardium·min^-1 in the TMLR, respectively (P<0.05); MLE were (12.04±3.04) in the AMI and (21.84±8.49)% in the TMLR, respectively (P<0.05). The volume density of mitochondria were (27.51±7.93)% in the AMI and (31.26±3.85)% in the TMLR, respectively (P>0.05). The area density of mitochondria were (1.25±0.18) μm^-1 in the AMI and (1.64±0.28) μm^-1 in the TMLR, respectively (P<0.01). The number density of mitochondria were (0.10±0.03) μm^-3 in the AMI and (0.18±0.05) μm^-3 in the TMLR, respectively (P<0.01). The average volume of mitochondria were (5.27±2.85) μm³ in the AMI and (2.80±0.54) μm³ in the TMLR, respectively (P<0.05). The average diameter of mitochondria were (2.06±0.36) μm in the AMI and (1.78±0.12)μm in the TMLR, respectively (P＜0.05). CONCLUSION: The study suggests that TMLR may effectively improve myocardial lactatic metabolism and protect the myocardial cells from ischemic injury in dogs with the AMI.     

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.     

Pathophysiological significance of ubiquition-proteasome system in myocardial infarction

Degradation of most proteins in eukaryotic cells is through the ubiquition-proteasome system (UPS). Recently, it demonstrated that UPS regulates cell apoptosis and cardiac hypertrophy. The differences of UPS regulation lie in E3 ligases, which specifically recognize targets and direct the ubiquitination process. Recent evidence suggests that atrogin-1/muscle atrophy F-box (Mafbx) and muscle RING finger 1 (MuRF1) may be critical mediators of the heart and muscle atrophy and hypertrophy. This review summarizes the possible relationship between UPS and cardiac dysfunction after myocardial infarction in order to inhibit cardiac dysfunction after myocardial infarction.     

Effect of pretreatment with 11,12-EET on myocardial ischemia/reperfusion injury in rats

AIM: To examine the effect of pretreatment with low-concentration of 11, 12-epoxyeicosatrienoic acid(EET) on myocardial ischemia/reperfusion injury in rats. METHODS: After tracheotomy, myocardial ischemia/reperfusion was produced by occlusion and release of the left anterior descending artery(LAD) of the rats. Ischemic preconditioning(IP) was made by two times of ischemia(5 min)/reperfusion(5 min). The experiment was conducted in three groups: control,IP and pretreatment with 11,12-EET(6.24×10^-8 mol/L), and each group was subdivided into two subgroups:A,the rats were subjected to ischemia(10 min)/reperfusion(10 min) and arrhythmias during the whole periods were monitored; The rats in B were subjected to ischemia(60 min)/reperfusion(30 min) and arrhythmias, cardiac funtion and myocardial infarction size were documented. RESULTS: Both IP and pretreatment with 11,12-EET could protect the heart against arrhythmias, cardiac disfunction and myocardial infarction. CONCLUSION: Pretreatment with 11,12-EET had protective effect on myocardium in case of ischemia/reperfusion, which was similar to ischemic preconditioning.     

Effect of angelica on myocardial fibrosis post myocardial infarction in rats

AIM: To investigate 1) the role of transforming growth factor-β₁ (TGF-β₁) and macrophage infiltration during the development of myocardial fibrosis (MF) in rats after myocardial infarction (MI);and 2) mechanisms of MF post-MI and the inhibitory effect of angelica.METHODS: Sprague-Dawley (SD) rats were subjected to MI by ligating the left anterior descending coronary artery.The animals were randomly divided into three groups: sham, MI and MI+angelica.After 24 hours of ligation, rats received angelica (20 mL·kg^-1·d^-1, ip) or saline.Left ventricular hemodynamics were measured and rats were killed at week 1, week 2 and week 4, respectively.Collagen content, macrophage infiltration and TGF-β₁ expression were examined in the non-infarcted area.RESULTS: ① In MI group, the numbers of macrophage and TGF-β₁ expression were significantly upregulated compared to sham at week 1 post-MI and remained elevated at week 4 (P<0.01).Angelica significantly decreased macrophage infiltration and TGF-β₁ expression (P<0.01 vs MI).② Collagen content was increased significantly in MI group compared to sham at week 2 and week 4 (P<0.01), and decreased in MI+angelica group (P<0.05 vs MI).③ Cardiac function was markedly decreased post-MI in MI group (P<0.01), and improved at week 4 in MI+angelica group (P<0.05).CONCLUSION: In MF post-MI, angelica may have an antifibrotic effect by decreasing macrophage infiltration and TGF-β₁ expression, by which reactive myocardial fibrosis is reduced, and cardiac function is improved.