Effect Of Mild Therapeutic Hypothermia(34 ?) On Hypertrophy Myocardial Ischemia-reperfusion Injury

Objective:To investigate the effect of PI3 K and NO on myocardial ischemia-reperfusion injury in hypertrophied myocardium,and to observe the relationship of MMP-9,MMP-2 and IL-1? In the mild therapeutic hypothermia(34 ?)on myocardial ischemia-reperfusion injury.Methods:Seventy-two healthy male Sprague-Dawley rats were provided by the Experimental Animal Science Department of Nanchang University.The rats were randomly divided into six groups: SHAM group;Control group;group(I/R group),,with 37? during ischemia for 30 min and reperfusion for 120min;ischemia/ reperfusion with mild therapeutic hypothermia at 34? group(34H+I/R group),with 34?of mild therapeutic hypothermia during reperfusion period;ischemia/reperfusion with mild therapeutic hypothermia and NOS inhibitor L-NAME group,with 34? of mild therapeutic hypothermia and the addition of NOS inhibitor L-NAME during reperfusion period;ischemia/reperfusion with mild therapeutic hypothermia and PI3 K inhibitor wortmannin group,with 34? of mild therapeutic hypothermia and the addition of PI3 K inhibitor wortmannin during reperfusion period.The SHAM group without any processing,the other groups were subjected constriction of the abdominal aorta just above the renal artery.Then record the index including the level of HR,LVSP,LVEDP,dp/dtmax and dp/dtmin at the time point of baseline,30 min before ischemia(T0);15min after reperfusion(T1),30 min(T2),60 min(T3),120 min(T4).Collection of perfusion fluid was used to detect the concentration of lactate dehydrogenase(LDH),creatine kinase(CK)and NO.At the end of 120 min reperfusion,detection of cardiac hypertrophy index.Six rats were randomly removed to evaluate myocardial infarction sizes by triphenyltetrazolium chloride staining(TTC).western blot were used to investigate PI3 K,IL-1?,MMP-2 and MMP-9 expression.Result:1.Cardiac hypertrophy indexThe left ventricular weight/body weight ratio in the hypertrophied hearts was higher after subjected constriction of the abdominal aorta just above the renal artery(P <0.05).2.Hemodynamic parametersThere was no significant difference each group balance period in the hemodynamic parameters(P> 0.05).At the time of T1,T2,T3,T4,compared with I/R group,HR was decreased in 34 H + I/R group,while there were no differences between the 34 H + I / R + L-NAME group,the 34 H + I/R + WORT group and I/R group at the same time point(P>0.05).3.The content of LDH and CKCompared with I/R group,the myocardial enzyme release in 34 H + I/R group was significantly lower than that in 34 H + I/R group(p <0.05).Compared with 34 H + I/R group,34 H + I/R + L-NAME group significantly increased myocardial enzyme release(p <0.05)4.The expression of PI3 K protein and production of NOThe expression of PI3 K protein was significantly increased in the 34 H + I/R group compared with I/R group(p <0.05),and the content of NO was significantly increased.In 34 H + I/R + L-NAME group and 34H+ I/R + WORT group,the high expression of PI3 K protein was decreased(p <0.05),and the NO production in hypertrophic myocardium was significantly decreased(p <0.05).5.Myocardial infarction sizeCompared with I/R group,the myocardial infarct size was significantly reduced in 34 H + I/R group(p <0.05).Compared with 34 H + I/R group,the myocardial infarct size in the L-NAME group and 34 H + I/R + WORT group was significantly enlarged after I/R injury(p <0.05).6.The expression of MMP-2,MMP-9 and IL-1? in myocardial ischemia-reperfusion injuryCompared with control group,the expression of MMP-2,MMP-9 and IL-1? protein in myocardium of I/R group was significantly increased(p <0.05).The expression of MMP-2 and MMP-9 were no significant differences between I/R group and 34 H + I/R group.Compared with I/R group,the expression of IL-1? in 34 H + I/R group was significantly lower than that in I/R group(p <0.05).34 H + I/R + L-NAME group and 34 H + I/R + WORT group,compared with 34 H + I/R group,MMP-2 and MMP-9 protein expression were no significant change(p >0.05)and IL-1? was significantly increased(p <0.05).Conclusion:1.Mild therapeutic hypothermia(34?)can reduce the hypertrophy of myocardial tissue LDH and CK release,reducing myocardial infarct size,and thus protecting hypertrophied myocardium against myocardial ischemia-reperfusion injury;2.NOS inhibitors L-NAME and PI3 K inhibitors can reverse the mild therapeutic hypothermia(34?)against ischemia-reperfusion injury on hypertrophied myocardium;3.The use of NOS inhibitors L-NAME and PI3 K inhibitors wortmannin was not able to express MMPs;4.NO may mediate Mild therapeutic hypothermia(34?)to improve inflammatory response,thereby protecting the hypertrophic myocardium.