| Objective:1.By establishing the model of neonatal rats with normobaric asphyxia,to observe the changes of the myocardial hypoxia-inducible factor-1αand serum ET-1 in neonatal rats after asphyxia and explore the relevance between them.2.To investigate the effects on the indexes of myocardial hypoxia-inducible factor-1αand serum ET-1 in neonatal rats after asphyxia by the pre-treatment of Xinmailong,and explore the possibly protective mechanism of Xinmailong in the hypoxia-ischemic myocardial injury.Methods:1.Model building and grouping : selecting ninety Sprague-Dawley(SD) rats(seven day-old,10g~15g),which were randomly divided into Control group (n = 30),Asphyxia group (n = 30),Xinmailong group (n = 30);and each group was randomly divided into three time points at six hours,twenty-four hours and seventy-two hours,there are ten rats at each time point. Control group:only to simulate the process of the model of neonatal rats with normobaric asphyxia,do not plug stopper and reoxygenation;Asphyxia group:carry on the model of neonatal rats with normobaric asphyxia;Xinmailong group:the effects of intraperitoneal (i.p.) injection of XML (5mg ? kg -1) administered five minutes before carring on the model of neonatal rats with normobaric asphyxia were studied.2.To determine the number of deaths,the level of CK and myocardial fine structure;The ET-1 activity was detected by radioimmunoassay;The myocardial HIF-1αactivity was measured by immunohistochemical method.3.Statistical methods:Factorial analysis,SNK-q test and Pearson correlation analysis.Results:1.The number of deaths :there was no death in Control group,and four rats died in Asphyxia group while only one died in Xinmailong group. 2.Myocardial enzyme CK:there was no obvious change at each time point in Control group;the level of CK activity increased in 6 hours,reached the peak in 24 hours,and declined in 72 hours in Asphyxia group,and each of them was significantly higher than that of in the same time point in Sham operated group(P<0.01);the level of CK in Xinmailong group activity was significantly higher than that of Sham operated group(P<0.01),while compared with that of Asphyxia group,each of them was significantly decreased(P<0.01).3.Serum levels of ET-1:there was no obvious change at each time point in Control group; the level of ET-1 activity increased in 6 hours,reached the peak in 24 hours,and declined in 72 hours in Asphyxia group,and each of them was significantly higher than that of in the same time point in Sham operated group(P<0.01);the level of ET-1 in Xinmailong group activity was significantly higher than that of in Sham operated group(P<0.01),while compared with that of Asphyxia group,each of them was significantly decreased(P<0.01).4.Myocardial expression of HIF-1α:there was no obvious change at each time point in Control group; the myocardial expression of HIF-1αactivity increased in 6 hours,reached the peak in 24 hours,and declined in 72 hours in Asphyxia group,and each of them was significantly higher than that of in the same time point in Sham operated group(P<0.01);the expression of HIF-1αin Xinmailong group activity was significantly higher than that of in Sham operated group(P<0.01),while compared with that of Asphyxia group,each of them was significantly decreased(P<0.01).5.The myocardial fine structure: myocardial cells were arranged uniformly and closely,no edema can be seen and dense nucleus were clearly visible in Control group ;in contrast of the same time point of in Asphyxia group, myocardial edema and infiltration of inflammatory cells can be reduced ,even no cell necrosis can be seen in Xinmailong group.6.HIF-1αpositively correlated with ET-1 in Asphyxia group (r=0.876,P<0.01).Conclusion:1.The expression of the myocardial hypoxia-inducible factor-1αand the level of serum ET-1 in neonatal rats after asphyxia increased,which suggests that HIF-1αand ET play an important part in the pathogenesis of asphyxia. 2.The relationship between myocardial HIF-1αexpression and serum level of ET-1 was positively related,which shows that HIF-1αmay control the target gene expression of ET-1 during asphyxia.3.Xinmailong can effectively reduce the number of deaths of neonatal rats,lessen myocardial enzyme,decrease the pathological changes of hypoxia-ischemic myocardial injury,its mechanism may be associated with a reduction of myocardial HIF-1αexpression and serum level of ET-1.
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