替米沙坦预处理对大鼠缺血再灌注损伤后心肌细胞凋亡及NF-κB表达的影响

Effects of telmisartan preconditioning on apoptotic myocytes and NF-κB expression in myocardium of rats with ischemia reperfusion injury

目的研究替米沙坦预处理对大鼠心肌缺血再灌注损伤(MIRI)后心肌细胞凋亡及核转录因子κB(nuclear factor-kappa B,NF-κB)蛋白表达的影响。方法健康雄性SD大鼠32只,随机分为4组:假手术组(Sham组)、缺血再灌注组(MIRI组)、替米沙坦预处理Ⅰ组(TⅠ组)和替米沙坦预处理Ⅱ组(TⅡ组),每组8只。TⅠ组灌胃替米沙坦5.0mg/(kg.d),TⅡ组灌胃替米沙坦10.0mg/(kg.d),其余每日灌胃等量生理盐水,持续一周。建立MIRI模型,光镜下观察心肌形态改变、测定血清CK-MB活性、TUNEL检测凋亡细胞及免疫组化测定NF-κBp65的表达。结果与Sham组相比,MIRI组与TⅠ、TⅡ组血清CK-MB活性、凋亡细胞、NF-κBp65表达明显升高(P<0.01);与MIRI组相比,TⅠ组血清CK-MB活性明显降低(P<0.01),凋亡细胞、NF-κBp65表达降低(P<0.05);TⅡ组血清CK-MB活性,凋亡细胞、NF-κBp65表达明显降低(P<0.01)。结论替米沙坦预处理可降低心肌缺血再灌注血清CK-MB的含量,抑制NF-κBp65的表达,抑制细胞凋亡,对大鼠急性心肌缺血再灌注损伤起保护作用,而高剂量组的保护作用优于低剂量组。

[ Objective ] To research the effects of telmisartan preconditioning on apoptotic myocytes and nuclear factor- kappa B（NF-κ B） expression in myocardium of rats with ischemia reperfusion injury. [ Methods ] 32 healthy male SD rats were randomly divided into 4 groups： sham group （Sham group, n=8）. myocardial isehemia reperfusion injury group （ MIRI group, n=8 ） and telmisartan preconditioning I group （T Ⅰ group,n=8） and telmisartan preconditioning Ⅱ group（T Ⅱ group, n=8）. The rats in T I group were administered with telmisartan （5.0mg/kg/d） by gastrogavage which was dissolved in the drinking water and the rats in T lI group were administered with telmisartan （10 0mg/kg/d）. The other rats were respectively administered with the same volume physiological saline by gastrogavage once per day for 7 days. Experimental animal model of MIRI in rats was achieved by ligating left anterior descending of coronary artery. Morphology changes in myocardium was observed by HE staining . Activity of CK-MB in serum was observed. TUNEL method was used todetect apoptotic myocytes in different groups. NF-κ Bp65 expression in myocardium were analyzed by immunohistochemistry. [ Resluts ] Comparing with the Sham group, activity of CK-MB, apoptotic myocytes and NF- s： Bp65 expression of the other three groups were significantly increased（P〈0.01）; Comparing with the MIRI group, activity of CK-MB of the T I group were significantly reduced（P〈0.01）, apoptotic myocytes and NF- K Bp65 expression were reduced（P〈O.05）; activity of CK-MB, apoptotic myocytes and NF- K Bp65 expression of the T 11 group were significantly reduced（P〈O.01）. [ Conclusion ] Telmisartan preconditioning can significantly decrease the levels of CK-MB in serum with acute myocardial ischemia reperfusion injury,can attenuate the expression of NF- K Bp65,and can attenuate apoptotic myocytes, especially high dosages group was better than low dosages group.