Endoxin antagonist up-regulates gene expression of sodium pump isoforms in rats with myocardial ischemia reperfusion injury

AIM: To observe the effect of endoxin antagonist,anti-digoxin antiserum,on endoxin level,ATPase activities,intramitochondrial total calcium concentration and gene expression of sodium pump isoforms in myocardium of rats with myocardial ischemia reperfusion (MIR).METHODS: Fifty-six male Sprauge Dawley rats were randomly divided into 7 groups.Sham operation group: silk suture threading the left anterior descending coronary artery without ligature;MIR group: left anterior descending coronary artery was subjected to 30 min ligation followed by 45 min reperfusion;normal saline group: MIR model was given 5 mL/kg normal saline;verapamil group: MIR model was given 5 mg/kg verapamil;low dose antidigoxin antiserum group: MIR model was given 8.6 mg/kg antidigoxin antiserum;middle dose antidigoxin antiserum group: MIR model was given 17.3 mg/kg antidigoxin antiserum;high dose antidigoxin antiserum group: MIR model was given 34.5 mg/kg antidigoxin antiserum.All drugs were injected into vessel via femoral vein within 5 min before reperfusion,respectively.After reperfusion,left ventricle myocardium samples were processed immediately in order to measure the activity of Na+ K+_ATPase and Ca2+_Mg2+_ATPase,endoxin level,intramitochondrial total calcium concentration and the experssion of α₁,α₂,α₃ and β₁ isoforms of sodium pump on mRNA and protein levels by RT-PCR and Western blotting and immunohistochemical assay,respectively.RESULTS: After MIR,the level of endoxin in myocardium was obviously increased.The activities of Ca2+_Mg2+_ATPase and Ca2+ Mg2+ ATPase in myocardial membrane were significantly decreased while intramitochondrial total calcium concentration increased.The gene expression of the α₁,α₂,α₃ and β₁ isoforms of sodium pump at both mRNA and protein levels were reduced markedly.Only the effect of verapamil on reducing intramitochondrial total calcium concentration was observed.Antidigoxin antiserum significantly reduced the level of endoxin in myocardium,restored the activities of Na+ K+_ATPase and Ca2+_Mg2+_ATPase,reduced intramitochondrial total calcium concentration,and up-regulated the expression of α₁,α₂,α₃ and β₁ isoforms of sodium pump at both mRNA and protein levels.CONCLUSION: MIR results in increase of endoxin secretion.The latter depresses the activity of Na+ K+_ATPase by down-regulating the gene expression of α₁,α₂,α₃ and β₁ isoforms of sodium pump in myocardial membrane,and also induces intramitochondrial calcium overload,thereby mediates MIR injury.     

Antagonistic effect of aminoguanidine on diabitic myocardial damage in rats

AIM:To investigate the mechanism of the antagonistic effect of aminoguanidine (AG) on diabitic myocardial damage in rats. METHODS:Morphology of myocardium in diabetic group and AG group were observed under transmission electron microscope (TEM). Activity of superoxide dismutase (SOD), nitric oxide synthase (NOS), inducible nitric oxide synthase (iNOS) and contents of malondialdehyde (MDA) were detected biochemically in myocardial homogenate. Nitrotyrosine (NT), which is the sign of peroxynitrite anion (ONOO^-), was detected using Western blotting. RESULTS:Under TEM, there was edema around nucleus of cadiocytes, part of inocommaes were breaked and Z lines were ambiguity, and part of costulaes and membranes of mitochondrion in cadiocytes were breaked or disappeared. The activity of NOS, iNOS and the content of MDA and NT increased in diabetic group as compared to control. The pathological changes of myocardium induced by diabetes were reversed in AG group, only part of costulaes of mitochondrion of cadiocytes disappeared, inocommaes were in order on the whole and only some lipid droplets deposited. The activity of NOS, iNOS and the content of MDA and NT in AG group decreased as compared to diabetic group. CONCLUSION:The protective effect of AG on diabitic myocardium may be through anti-lipid peroxidation and decreasing the content of ONOO^-.     

外源钙对根际低氧胁迫下黄瓜植株钾、钙、镁离子含量和ATPase活性的影响

以黄瓜(Cucumis sativus L.)'新泰密刺'品种为材料,采用营养液栽培,研究了外源Ca2+对根际低氧胁迫下幼苗植株离子含量和ATPase活性的影响。结果表明,常钙低氧处理植株体内K+、Ca2+、Mg2+含量和质膜、液泡膜、内质网膜ATPase活性显著降低;营养液增施4mmol·L-1CaCl2明显缓解了低氧胁迫对植株的伤害,根中K+、Ca2+、Mg2+含量,根系质膜、液泡膜、内质网膜H+-ATPase和Ca2+-ATPase活性,显著高于常钙低氧处理,接近或达到对照水平;根际低氧胁迫下营养液增施Ca2+通道抑制剂La3+(50μmol·L-1H+)显著,降低了幼苗体内K+、Ca2+含量,但对Mg2+含量影响不显著,营养液增施La3+显著降低了质膜H+-ATPase和Ca2+-ATPase的活性,但对液泡膜,内质网膜H+-ATPase和Ca2+-ATPase活性影响不显著。外源钙通过增加黄瓜体内矿质营养离子的吸收和转运,维持质膜、液泡膜和内质网膜ATPase活性,从而缓解低氧胁迫对植株造成的伤害,增强黄瓜植株的低氧耐性。     

Effects of heptanol preconditioning on structure,function and Cx43 content of mitochondria in rabbit model of myocardial ischemia/reperfusion injury

AIM: To investigate the effects of heptanol preconditioning on the changes of structure, function and connexin 43 (Cx43) content in mitochondria in a rabbit model of myocardial isehemia-reperfusion (IR) injury. METHODS: In anesthetized open-chest rabbits, the left anterior descending artery (LAD) was occluded for 30 min and reperfused for 4 h. Sixty-four rabbits were randomly divided into 4 groups (n=16 in each group): sham operation group (sham group), ischemia-reperfusion group (IR group), ischemic preconditioning group (IP group) and heptanol preconditioning group (HT group). All rabbits in the 4 groups were killed 4 h after reperfusion. Myocardial infarct size was determined at the end of the experiment. Mitochondria was isolated by centrifugations. The ultrastructural changes of the mitochondria were observed under electronic microscope. The mitochondrial membrane potential, Ca2+ concentration, MDA content and SOD activity of myocardial mitochondria were also examined. The content of mitochondria Cx43 was detected by Western blotting. RESULTS: Compared to IR group, the myocardial infarct size was significantly reduced in IP (18.97%±2.80%) and HT (19.97%±3.80%) groups, the damage of mitoehondrial ultrastructure was milder (P<0.05), mitochondrial membrane potential was significantly higher and Ca2+ concentration was much lower (P<0.01) in IP group and HT group. No significant difference of MDA content and SOD activity in myocardial mitochondria between IR group and HT group was found. However, MDA content were much lower and SOD activity was significantly higher in IP group as compared to IR group (P<0.01). Compared to sham group, the mitochondria Cx43 expression was distinctly decreased compared to IR group (P<0.05) and no significant difference was found between IP group and HT group (P>0.05). CONCLUSION: Heptanol preconditioning protects myocardium from ischemia-reperfusion injury. The mechanism may be related to increasing in mitochondrial membrane potential, alleviating Ca2+ overload in myocardial mitochondria and attenuating the decrease in mitochondria Cx43 expression induced by isehemia-reperfusion.     

Changes of myocardial glycogen content and right ventricular function in hypoxia swimming rats

AIM: To investigate the changes of myocardium glycogen content and the relation ship between changes of the myocardial glycogen content and the myocardial function. METHODS: Male Wistar rats were placed in (hypoxia rats) and made to swim in (hypoxia swimming rats) a hypobaxic chamber simulating an altitude of 5 000 m above sea level. The content of myocardium glycogens was determined by colorimetry. RESULTS: The myocardium
glycogen content of rats significantly reduced along with the prolongation of hypoxic exposure and approached to control level in hypoxia swimming rats. The myocardial function of right ventricule was improved significantly compared with control group.CONCLUSION: Moderate exercise (swimming) is beneficial to hypoxic adaptation of rats under the condition of chronic hypoxia.     

Effect of taurine on action potentials and ATP-sensitive posstiaum channel activity during hypoxia in ventricular muscle of guinea pig

AIM: To study the effects of taurine on ATP sensitive potassium channel (IK-ATP) during hypoxia in single ventricular myocyte. METHODS: The model of myocardial hypoxia was induced by unmixed and saturated nitrogen. IK-ATP activities were measured by whole-cell patch clamp recording. RESULTS: Activities of IK-ATP in the cell membrane of hypoxia ventricular myocyte significantly increased, compared to that in the normal. Extracellular injection of taurine (5，10，20 mmol/L) inhibited the increase in the IK-ATP activity in the hypoxia myocardium in a concentration-depend manner. Injection of taurine also recovered shorten APD during hypoxia. CONCLUSIONS: Taurine produces its cardioprotective effect by inhibiting the activity of IK-ATP in the hypoxia cardiomycytes of guinea pig. The results suggest that the depletion of taurine during myocardial hypoxia contributes to the early activation of the KATP channel.     

Chronic inhibition of cilazapril on pulmonary vascular and myocardial cell proliferation in hypoxic rats

AIM: To explore the mechanism of cilazapril inhibiting proliferation of pulmonary vascular and myocardial cells in hypoxic rats. METHODS: 30 male Wistar rats were used and divided into three groups: normal control (group A)， intermittent hypoxia for 4 weeks (group B) and intermittent hypoxia for 4 weeks plus cilazapril treatment (group C). The cell proliferation and structural remodeling in pulmonary vasculature and myocardium during hypoxia were studied by biochemical analysis, radioimmunoassay, immunohistochemistry, terminal deoxyuridine tripnosphate nick end labeling and correlated with hemodynamic. RESULTS: (1) The mean pulmonary artery pressure (mPAP) and the right ventricle to left ventricle plus ventricular septum ratio (R/L±S) were significantly higher in the hypoxic rat than that in control animals, while increased thickness of the pulmonary vascular wall and vascular lumen with decrease in the caliber as well as myocardial hypertrophy were observed in hypoxic rats. (2) The proliferative index (PI) of pulmonary arteria and myocardium was significantly higher in group B and C than that in group A. The distribution of ET-1 positive cells was seen in pulmonary arterial wall and cardiomyocytes. The ET-1 immunoreactivity was group B>group C>group A by turns. (3) The concentrations of plasma endothelin-1 (ET-1) and angiotensin converting enzyme (ACE) were significantly higher in group B than that in group A. However, the ET-1 and ACE were significantly lower in group C than those in group B. (4) The ET-1 and ACE had a significant positive correlation with R/L+S, mPAP and PI, respectively. The multivariate linear regression analysis revealed that ET-1 and ACE were major factor affecting PI. CONCLUSION: The pulmonary vascular and myocardial structural remodeling are one of the pathogenesis accompanied with excessive cell proliferation in hypoxic pulmonary hypertension (PH). Cilazapril effectively prevents and treats the hypoxic PH by inhibiting cell proliferation and structural remodeling of pulmonary circulation, as induced by ET-1 and ACE.     

Effects of ischemic preconditioning on oxidative stress and mitochondrial function in young and old rat myocardium with ischemia/reperfusion

AIM: To study the protective effect of ischemia preconditioning (IPC) on ischemia/reperfusion (IR)-damaged myocardium in young and old rats. METHODS: Male Wistar rats aged at 3 months (young) and 20 months (old) were used to establish myocardial IPC model and IR model with the method of Langendorff heart perfusion. The rats were divided into young ischemia/reperfusion (YIR) group, young ischemic preconditioning (YPC) group, old ischemia/reperfusion (OIR) group and old ischemic preconditioning (OPC) group. Transmission electron microscopy was used to observe the ultrastructural changes of myocardial tissue and myocardial mitochondria. The myocardial infarction area was determined by TTC staining. The lactate dehydrogenase (LDH) content in coronary effluent fluid and the levels of superoxide dismutase (SOD) and malondialdehyde (MDA) in myocardial tissues were detected by the method of colorimetry. The levels of nitrated and carbonylated proteins in myocardial tissue were measured by ELISA. The myocardial cell apoptosis was analyzed by TUNEL assay. The mitochondrial respiratory function and mitochondrial permeability transition pore opening induced by calcium load were evaluated by oxygen electrode method. RESULTS: Compared with YIR group, the myocardial infarction area in YPC group was obviously smaller, SOD activity in myocardial tissues increased, LDH activity in coronary effluent fluid and the content of MDA decreased, and the levels of nitrated and carbonylated proteins in the cardiac tissues reduced. In YPC group, the mitochondrial membrane structure appeared intact, cristae of the mitochondria showed close arrangement, and the matrix was compressed under the electron microscope. Myocardial mitochondrial respiratory control rate, state Ⅲ oxygen consumption and the P/O ratio in YIR group all significantly increased, proton leak decreased, mitochondrial swelling induced by calcium distinctly reduced, and myocardial apoptosis rate declined. No significant difference of the above indexes between OIR group and OPC group was observed. Compared with YPC group, myocardial ultrastructural damage increased clearly, cardiac oxidative stress increased, mitochondrial respiratory function declined, and cell apoptosis and necrosis increased in OPC group. CONCLUSION: Ischemic preconditioning has protective effect against myocardial IR injury in young rat hearts, while old rat hearts were less sensitive to ischemic preconditioning, leading to bluntness of cardioprotection with IPC in aging hearts. This may be related to mitochondrial injury and severe cellular apoptosis caused by increase of cardiac oxidative stress levels in the aging ischemic preconditioning heart.     

Alteration of local renin-angiotensin system of dogs with myocardial ischemia and external counterpulsation treatment

AIM:To examine the alteration of local renin-angiotensin system of dogs with myocardial ischemia and external counterpulsation treatment and its mechanism. METHODS:Acute myocardial ischemia was induced by occluding the LAD of ischemic and ECP groups. The tissue renin activity and angiotensin(AngⅡ) level in ischemic myocardium and aorta were measured. The expression of angiotensinogen and renin mRNA were detected by RT-PCR. RESULTS:Renin activity, AngⅡ level in ischemic myocardium and AngⅡ level in aorta of ECP group were lower than those of MI group. Except for renin in ischemic myocardium, angiotensinogen mRNA and renin in ischemic myocardium and angiotensinogen mRNA in aorta of ECP group were reduced to normal level. CONCLUSION:The inhibitory effect of ECP on cardiovascular renin activity and angiotensinogen gene expression could be one of the mechanisms by which ECP protects ischemic myocardium.     

Effects of external counterpulsation on renin-angiotensin system and hemodynamics in dogs with myocardial ischemia

AIM:To examine the effect of external counterpulsation(ECP) on renin-angiotensin system(RAS) and hemodynamics in dogs with myocardial ischemia and their relationship. METHODS:Acute myocardial ischemia was induced by occluding the left anterior descending of the dogs. The local renin activity, angiotensin Ⅱ(AngⅡ) level, angiotension-converting enzyme(ACE) activity were tested by biochemical methods and hemodynamics was recorded by a 8-channel physiological recorder.RESULTS:Ischemia could actiivate renin,ACE and AngⅡ in cardiovasculature and ECP reduced them except for renin in ischemic myocardium. Ischemia also could activate RAS in lung and kidney, which play an important role on circulating RAS, and ECP reduced them. Furthermore, ECP could improve hemodynamics and there existed a close relationship between local AngⅡlevel and hemodynamics. CONCLUSION:ECP can reduce local RAS and improve hemodynamics in dogs with myocardial ischemia, which might be one of mechanisms underlying the protective effect of ECP on ischemic myocardium.     

Protective effect and the possible mechanism of Nano-Se on myocardium of experimental diabetes mice

AIM: To observe the protective effect of Nano-Se on myocardium of experimental diabetes mice. METHODS: Sixty healthy male KM mice were chosen, ten of which were selected randomly as the normal control group. After fasted for 24 h, the rest 50 mice were injected with streptozotocin (STZ, 50 mg/kg) intraperitoneally for 5 d. At 7th d, the blood-sugar was measured from vena caudalis, 40 mice, of which blood-sugar exceeded 16.65mmol/L, were selected and randomized into 4 groups: the positive control group, low dose (25 μg/kg) Nano-Se group, mid dose (50 μg/kg) Nano-Se group, high dose (50 μg/kg) Nano-Se group. All mice were given intragastric administration of 0.2 mL normal saline and corresponding dose of Nano-Se. The body weights were measured every week, and the dose of which was adjusted according to the change of the body weights. 8 weeks later, the mice were killed and cardiac muscle of the left ventricle was taken. The myocardium was prepared to 10% homogenate for measuring SOD, GSH-Px activity and MDA content. The myocardial cell apoptosis was measured by TUNEL. The expressions of Bc1-2 and Bax proteins were determined by immunohistochemistry. RESULTS: Compared to normal group, the SOD and GSH-Px activities in positive control group decreased, MDA level increased, the rate of myocardial cell apoptosis increased significantly, Bc1-2 protein expression deceased and Bax protein expression increased. Compared to positive control group, the SOD and GSH-Px activities in low and mid dose Nano-Se groups expression increased, MDA level decreased, myocardial cell apoptosis rate decreased, Bc1-2 protein expression increased and Bax protein expression decreased. Moreover, the SOD and GSH-Px activities in high dose Nano-Se group decreased obviously compared to those in mid dose Nano-Se group. MDA level and myocardial cell apoptosis rate increased, Bc1-2 protein expression decreased and Bax protein expression increased, no significant difference in SOD, GSH- Px activity, MDA level and myocardial cell apoptosis rate was observed compared with positive control group. CONCLUSION: The damage of cardiac muscle is alleviated when a certain dose of Nano-Se is supplied to diabetes mice. The protective mechanism may be related to antioxidation, blood-sugar adjustment and the increase of Bc1-2 expressing.     

Influence of ovariectomy and estrogen replacement on gene expression profile of myocardium in rats

AIM:To investigate the influence of ovariectomy and estrogen replacement treatment on profile of gene expression in myocardium by cDNA microarray,and to characterize the targeting genes of estrogen.METHODS:cDNA microarray containing 1 400 rat cDNAs was used to study the genes differentially expressed in myocardium between sham (Ⅰ),ovariectomy (Ⅱ,OVX) and estrogen replacement treatment (Ⅲ,OVX+E2) group.Then down-regulated genes in myocardium of OVX rats were further confirmed by RT-PCR.RESULTS:177 genes were differentially expressed in myocardium between sham and OVX rats,with 91 genes up-regulated and 86 genes down-regulated in OVX rats.164 genes were differentially expressed in myocardium between OVX and OVX+E2 rats,with 113 genes up-regulated and 54 genes down-regulated in OVX rats.There were 54 genes differentially expressed in OVX compared to sham and OVX+E2.They are involved in membrane channels and transporters (18),cell receptors (9),intracellular transducers/effectors/modulator (7) and metabolism (6).Most of the genes (45) were down-regulated in OVX rats and up-regulated in OVX+E2 rats.RT-PCR test confirmed the results of cDNA microarray.CONCLUSIONS:Long-term estrogen replacement may influence the expression of genes involved in membrane channels and transporters,cell receptors,intracellular transducers/effectors/ modulator and metabolism.Long-term estrogen replacement has some beneficial effects on ionic concentration and cardiac function which partially comes from the results of influence of expression on Na+,K+-ATPase and Na+/H+ exchanger.Estrogen has an inhibitory effect on the expression of dopamine receptor,which partially clarify the myocardial protection of estrogen.     

Effects of ganoderma spores on apelin expression in rats with myocardial ischemia injury induced by isoproterenol

AIM: To investigate the changes of apelin in blood and myocardium, and the protective mechanisms of ganoderma spores on myocardial ischemia injury induced by isoproterenol in rats. METHODS: The model of myocardial ischemia injury was induced by subcutaneous injection of high dose isoproterenol. Enzyme linked immunosorbent assay (ELISA) was used to measure the apelin contents in blood and myocardium. Semi-quantitative RT-PCR was used to measure the apelin mRNA level in myocardium. Electron microscope was used to observe the pathomorphological changes of myocardium. Ganoderma spores was administered i.g. for 7 weeks. RESULTS: Compared with the normal control group, the apelin contents in blood and myocardium and the apelin mRNA level in myocardium were significantly decreased in the model group (P＜0.01). Compared with the model group, the apelin contents in blood and myocardium and the apelin mRNA level in myocardium were obviously elevated in the ganoderma spores groups (P＜0.01 or P＜0.05). Meanwhile, the NO contents in blood and myocardium were also obviously elevated. The pathological damage of myocardium was obviously relieved. CONCLUSION: The results suggest that the protective mechanisms of ganoderma spores on myocardial ischemia injury may be related to the elevation of apelin contents and the mRNA level.     

Mechanism of mesenteric lymph reperfusion aggravates multiple organ injury in superior mesenteric artery occlusion shock rats

AIM: To explore the mechanism of mesenteric lymph reperfusion (MLR) aggravates multiple organ injury in superior mesenteric artery occlusion (SMAO) shock rats. METHODS: Male Wistar rats were randomly divided into 4 groups: in sham group, only anesthetization and operation were performed; in MLR group, occlusion of mesenteric lymphatics (ML) for 1 h followed by 2 h of reperfusion; in SMAO group, occlusion of superior mesenteric artery (SMA) for 1 h followed by 2 h reperfusion; in MLR+SMAO group, occlusion of SMA and ML for 1 h followed by 2 h of reperfusion. The homogenates of liver, kidney, myocardium and lung were prepared for determining the activities of free radical, nitric oxide, myeloperoxidase (MPO) and cell membrane ATPase. RESULTS: The MDA, NO contents and NOS, MPO activities of multiple organic homogenate in SMAO and MLR+SMAO group were higher than those in sham and MLR group, and these indexes in MLR+SMAO were increased significantly than those in SMAO group. The SOD and ATPase activities of muliple organic homogenate in SMAO and MLR+SMAO group were lower than those in sham and MLR group, and those in MLR+SMAO group was decreased obviously than those in SMAO group. CONCLUSION: The MLR enhances the multiple organ free radical injury, NO synthesis and release, PMN detention and decreases the activity of cell membrane ATPase, aggravating the major organs injury in SMAO shock rats. Intestinal lymphatic pathway plays an important role in the pathogenesis of SMAO shock.     

Mechanisms underlying the protective effect of renal ischemic preconditioning on ischemia-reperfusion myocardium of rabbits

AIM: To investigate the mechanisms underlying the protective effect of kidney ischemic preconditioning on rabbit myocardium in case of ischemia-reperfusion and the possible role of oxygen free radicals in the process. METHODS: Animals were divided into four groups: ischemia/reperfusion(I/R), classical ischemic preconditioning(CIPC), kidney ischemic preconditioning (KIPC) and superoxide dismutase in combination with kidney ischemic preconditioning(SOD+KIPC). The endo genous myocardial pretective material, nitric oxide(NO) and 5'-nucleotidase(5'-NT) were checked in four groups. RESULTS: As compared with I/R group, both CIPC and KIPC could ameliorate left ventricular function, reduce plasma PLA₂ activity and arrhythogenic rate also, the myocardial 5'-NT and NO production were significantly higher than that of the rabbit of I/R group. However, the protective effect on rabbit myocardium was significantly weakened by the SOD administration before the ischemic preconditioning. CONCLUSION: Protective effect of KIPC on myocardium may be due to increase in endo genous myocardial protective materials, oxygen free radicals may play an important role in the endo genous myocardial protective material release.     

Effects of halothane and sevoflurane on the function,metabolism and Ca2＋-ATPase activity of ischemic myocardium

AIM: To study the effects of 1. 5 MAC halothane and sevoflurane on ischemic myocardium. METHODS: The isolated rat heart were perfused with halothane and sevoflurane and HR, LVEDP, LVDP, +dp/dt, -dp/dt, coronary flow (CF), the myocardial ATP content and Ca²⁺-ATPase activity were determined before and 10 min and 25 min after ischemia. In the meantime, LVP was recorded during 25 min ischemia. RESULTS: 1. 5MAC sevoflurane significantly increased CF in normal isolated rat hearts. Both halothane and sevoflurane depressed myocardial contractile function, increased normal myocardial energy storage. After 10 min ischemia, the decrease of myocardial ATP content were slowed down by halothane and sevoflurane, especially halothane. During 25 min of ischemia, the onset time of contracture was significantly delayed, and the contracture intensity was alleviated by halothane, but not sevoflurane. CONCLUSION: Halothane has better protective effect on ischemic myocardium than sevoflurane through preventing the decrease of myocardial ATP content and Ca²⁺-ATPase activity during ischemia.     

Effect of cilazapril on pulmonary vascular endothelial dysfunction in hypoxic rats

AIM:To study the effect of cilazapril on pulmonary vascular endothelial dysfunction in hypoxic rats. METHODS:The structure and function of endothelium in hypoxic rats were studied by biochemical analysis, radioimmunoassay, transmission electron microscope and correlated with hemodynamic. RESULTS:1) The change and damage of ultrastructure in endothelial cell (EC) were obsevered in hypoxic rats. 2) The contents of plasma nitric oxide (NO) and superoxide dismutase (SOD) activity in blood as well as endothelial nitric oxide synthase (eNOS) activity in the lung tissue were significantly lower in the hypoxic rat than those in contral animals. The concentrations of plasma endothelin-1(ET-1) and angiotensin converting enzyme(ACE) as well as malondialdehyde(MDA) were significantly higher in the hypoxic rat than these in contral animals. The relaxing and contracting factors had a significant positive/negative correlation with mean pulmonary artery pressure (mPAP). 3) Cilazapril significantly decreased the level of ET-1 and ACE and significantly increased the level of NO and activity of eNOS and SOD. At the same time, cilazapril extenuated hypoxia-induced injuries of EC. CONCLUSION:The results indicate that damaging structure and dysfunction of EC existes in hypoxic rats. The cilazapril effectively preventes and treates the chronic hypoxic PH by relieving the injury and improving secretion in EC.     

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.     

Aerobic exercise protects cardiac function of T2DM mice by activation of PI3K (p110α)/Akt signaling pathway

AIM: To study the protective effect of aerobic exercise on cardiac dysfunction in mice and its mechanism, and to provide theoretical and practical basis for the exercise therapy of diabetic cardiac dysfunction.METHODS: The mice were divided into normal control non-exercise (NNC) group, normal control exercise (ENC) group, diabetic non-exercise (NDM) group and diabetic exercise (EDM) group. At the end of the experiment, the cardiac function was evaluated by echocardiography. The pathological changes of the myocardial tissues and the development of fibrosis were observed. The mRNA expression of ANP, and the protein levels of PI3K (p110α) and Akt were determined. RESULTS: The decrease in cardiac function of diabetic mice was observed, and the cardiac function recovered after exercise intervention (P<0.05). Under light microscope with HE and Masson staining, the myocardial structure in NDM group was in extreme disorder, cell arrangement was not neat, and the degree of fibrosis increased, but the myocardial damage was improved in ENC group. Compared with NNC group, the mRNA expression of ANP in the myocardium of diabetic mice was up-regulated (P<0.05). The protein levels of PI3K (p110α) and Akt were decreased (P<0.05), and the cascade was inactivated. Compared with NDM group, the mRNA expression of ANP was down-regulated and the protein levels of PI3K (p110α) and Akt were up-regulated in EDM group (P<0.05). CONCLUSION: Diabetes results in myocardial damage in mice, and reduces cardiac function. Exercise intervention alleviates the heart dysfunction induced by high glucose via activating PI3K(p110α)/Akt signaling pathway to protect the structure and function of the myocardium.