压力超负荷大鼠心肌血红素加氧酶-1表达与氧化应激水平的相关性

目的:探讨压力超负荷大鼠心肌血红素加氧酶-1(HO-1)表达水平与心肌氧化应激水平的关系。方法:将40只SD大鼠随机抽取8只作为假手术组(Sham组),其余32只大鼠采用腹主动脉缩窄术制备压力负荷模型,将术后存活的22只大鼠随机分为模型组(Model组,n=7)、丹参酮ⅡA组(TanⅡA组,n=7)及丹参酮ⅡA+HO-1抑制剂组(TanⅡA+Zn PP组,n=8)。术后4周造模成功并开始给药,疗程为4周。8周后检测心脏质量指数、左心室质量指数,观察心肌组织HE染色,比色法检测心肌氧化应激水平,Western blotting法检测心肌HO-1的蛋白表达水平。结果:1)与Sham组比较,Model组大鼠心脏质量指数和左心脏质量指数明显升高(P0.01);与Model组比较,TanⅡA组和TanⅡA+Zn PP组心脏质量指数和左心脏质量指数均有不同程度下降,而TanⅡA组下降更为显著(P0.01)。2)HE染色结果显示,与Sham组比较,Model组大鼠心肌纤维化程度加重;与Model组相比,TanⅡA组和TanⅡA+Zn PP组心肌组织形态学均有不同程度的改善,而TanⅡA组改善更为明显。3)TanⅡA组血清超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)水平高于Model组和TanⅡA+Zn PP组(P0.01),MDA水平低于Model组和TanⅡA+Zn PP组(P0.01)。4)TanⅡA组心肌HO-1的蛋白表达水平高于其余3组(P0.01)。结论:丹参酮ⅡA可以提高心肌HO-1表达水平,增强压力负荷大鼠心肌抗氧化能力,减缓心室重构进程。

The Relationship between Oxidative Stress Level and the Expressions of Myocardial Haem Oxygenase-1 of Pressure Overloaded Rats

Objective: To discuss the relationship between the expressions of myocardial haem oxygenase (HO)-1 and oxidative stress level of pressure overloaded rats. Methods: Eight rats were randomly chosen as sham operation group (Sham group) from forty SD rats, the other 32 rats accepted abdominal aortic constriction to prepare pressure overloaded models, 22 rats remaining alive after the surgery were randomized into three groups: the model group (Model group, n=7), tanshinone ⅡA group (Tan ⅡA group, n=7) and tanshinone ⅡA and HO-1 inhibitor group (Tan ⅡA+ZnPP group, n=8). The models were successfully made in four weeks after the surgery and began to dose, and the course was four weeks. In eight weeks, cardiac mass index and left ventricular mass index were detected in eight weeks, myocardial tissue was observed after HE staining, myocardial oxidative stress level detected by colorimetry and the expressions of HO-1 protein by Western blotting method. Results: 1) compared with Sham group, cardiac mass index and left ventricular mass index of the rats in Model group raised obviously (P＜0.01); compared with Model group, cardiac mass index and left ventricular mass index of the rats in Tan ⅡA+ZnPP group decreased to different degrees, while the decrease of Tan ⅡA group was more notable (P＜0.01). 2) HE staining results showed that, compared with Sham group, myocardial fibrosis in the rats of Model group aggravated; compared with Model group, myocardial histomorphologyin Tan ⅡA group and Tan ⅡA+ZnPP group improved to different degrees, while the improvements of Tan ⅡA group were more notable. 3) Tan ⅡA group was higher than Tan IIA+ZnPP group in the levels of SOD and GSH Px (P＜0.01), while lower than Model group and Tan ⅡA+ZnPP group in the level of MDA (P＜0.01). 4) Tan ⅡA group was higher than the other three groups in the expression of myocardial HO-1 protein (all P＜0.01). Conclusion: Tan ⅡA could raise the expression of myocardial HO-1, enhance myocardial oxidation resistance of pressure overloaded rats and slow down the progression of ventricular remodeling.