| Objective To investigate the mechanism of heavy alcohol consumption in a short term on rat myocardium injury and the protection of AT2 receptor blocker Valsartan.Methods 31,6-7 weeks, male Wistar rats were divided into 4 groups randomly: Control group(C group,5 rats), Alcohol group(A group,10 rats), Low-dose Valsartan group(LD group,8 rats),High-dose Valsartan group(HD group,8 rats). They were supplied water and animal feeds, but all of them were administered different alcohol dose and medicine via intragastric tube:C group were administered water, A group were administered alcohol(6.4g/kg), LD group were administered alcohol(6.4g/kg) and Valsartan(15mg/kg), HD group were administered alcohol(6.4g/kg) and Valsartan(30mg/kg).9 weeks later, we observed the changes of cardiac ultrastructure and function with echocardiography and electron microscope, measured body weight(BW) and heart weight(HW), determined mRNA expression of TNF-a, ET-1, ACE, AGT, AT1 receptor, AT2 receptor by RT-PCR and hydroxyproline content by Sample Alkaline Solution and relationship among the index. Results (1) After 9 weeks, the body weight of C group increased compared to other groups(P<0.01). There was significant difference among these groups in HW, A group and LD(P<0.01), A group and HD group(P<0.01), LD and HD(P<0.01). There was significant difference among A group and other groups in heart weight over body weight(P<0.01). (2) The LVDd, LVDs of A group was larger than C group's and other groups(P<0.05), and IVSs, IVSd were thinner than other groups(P<0.05). there was no significant difference among four groups in LVPWs and LVPWd(P>0.05). There was no significant difference among four groups in LVEF, SV, FS(P>0.05). E peak, Ea/Aa, Aa, Ea in A group decreased compared to other groups, and there was siginificant difference among C group,LD group and HD group in E peak, Ea/Aa (P<0.05). (3) Ethanol-induced ultrastructural damage mostly involved mitochondrial structural changes including mitochondrial reduction in the number of cristae and endoplasmic reticulum dilation, perinuclear space widening, myocardial cell swelling, in comparison with LD group and HD group.(4) There was no significant difference between A group and other groups in the mRNA expression of AT1 receptor and AGT. The mRNA expression of ACE, ET-1, TNF-a increased in A group(P<0.05), but AT-2 receptor mRNA decreased in A group(P<0.05). (5) Hydroxyproline content increased in A group compared to other groups(P<0.05). (6) Pearson correlation analysis showed, ACE and AT2 receptor mRNA were in negative correlation(r=-0.403, P=0.046), ACE and ET-1mRNA, hydroxyproline content were in positive correlation(r=0.527, P=0.007; r=0.536, P=0.006), hydroxyproline content and TNF-amRNA, ET-1mRNA were in positive correlation(r=0.502, P=0.011; r=0.620, P=0.001). Hydroxyproline is dependent variable, ACE, TNF-a, ET-1 are independent variable, only ET-1(X) is indepent risk factor by multiple stepwise regression analysis. Equation is Y=0.607+0.330X(R2=0.385 F=14.398 P=0.001). Conclusion Local renin angiotensin system was activated by short-term and heavy alcohol consumption, and the mRNA expression of ACE, TNF-a, ET-1 and hydroxyproline content increased, finally impaired ultrastructure and diastolic function of myocardium, and Angâ…¡receptor blocker(Valsartan) may protect the myocardium from damage. |
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