桂枝汤桂枝白芍不同比例配伍对盐敏感高血压大鼠氧化应激和心肌细胞凋亡的影响

Effects of different compatibilities of Cinnamomi ramulus and Paeoniae radix alba in Guizhi Decoction on oxidative stress and cardiomyocyte apoptosis in salt-sensitive hypertensive rats

目的:探讨桂枝白枝汤桂芍不同比例配伍对盐敏感高血压大鼠氧化应激和心肌细胞凋亡的影响及作用机制。方法:雄性Dahl盐敏感大鼠采用高盐饲料造模,随机分为低盐空白对照组(NS组)、高盐模型对照组(HS组)、桂芍1∶1组(桂枝汤中桂枝∶白芍量1∶1)、桂芍1∶2组(桂枝汤中桂枝∶白芍量1∶2)、桂芍2∶1组(桂枝汤中桂枝∶白芍量2∶1),每组8只。药物连续干预4周后测量各组大鼠血压并观察心肌形态学变化,同时检测大鼠心肌组织8-OHdG含量及Bax、Bcl-2、cleaved Caspase-3、MnSOD蛋白表达水平。结果:与NS组大鼠比较,HS组大鼠平均动脉压、LVPWd、LVmass显著升高(P<0.01),心肌组织形态出现明显病理改变,心肌细胞排列紊乱,有明显水肿和大量炎性细胞浸润,心肌细胞凋亡率显著增加(P<0.01),心肌组织中的8-OHdG阳性细胞数显著增加(P<0.01),Bax、cleaved Caspase-3蛋白表达水平显著升高(P<0.01),Bcl-2、MnSOD蛋白表达水平显著下降(P<0.01)。与HS组比较,各给药组大鼠平均动脉压、LVPWd、LVmass显著降低(P<0.05,P<0.01),心肌组织病理改变减轻,心肌细胞凋亡率显著降低(P<0.05,P<0.01),心肌组织8-OHdG阳性细胞数显著减少(P<0.01),Bax、cleaved Caspase-3蛋白表达水平显著下降(P<0.01),Bcl-2、MnSOD蛋白表达水平升高(P<0.01),其中桂芍1∶1组各项指标较桂芍1∶2组、桂芍2∶1组均改善更为明显。结论:桂枝汤能有效抑制盐敏感大鼠的氧化应激和心肌细胞凋亡,其机制可能与增强抗氧化酶的表达和调控凋亡相关的蛋白有关,且桂枝汤桂芍1∶1组减轻氧化应激,抑制心肌细胞凋亡效果最好。

Objective:To investigate the effects of different compatibilities of Cinnamomi ramulus and Paeoniae radix alba in Guizhi Decoction on oxidative stress and cardiomyocyte apoptosis in salt-sensitive hypertensive rats and its mechanism.Methods:Male Dahl salt-sensitive rats were modeled with high-salt feed.They were randomly divided into low-salt blank control group,high-salt model control group,Guishao(Cinnamomi ramulus:Paeoniae radix alba)1∶1 group,Guishao 1∶2 group,Guishao 2∶1 group,8 rats in each group.After 4 weeks of continuous drug intervention,the blood pressure of each group was measured and the morphological changes of the heart were observed.At the same time,the levels of 8-OHdG and the expression levels of Bax,Bcl-2,cleaved Caspase-3,and MnSOD in myocardial tissue of rats were measured.Results:Compared with rats in NS group,mean arterial pressure,LVPWd and LVmass in HS group were significantly increased(P<0.01),myocardial tissue morphology showed significant pathological changes,cardiomyocytes are arranged disorderly,with obvious edema and large number of inflammatory cell infiltration,myocardial cell apoptosis rate significantly increased(P<0.01),the number of 8-OHdG positive cells in myocardial tissue significantly increased(P<0.01),Bax,cleaved Caspase-3 protein expression levels significantly increased(P<0.01),Bcl-2,MnSOD protein expression levels significantly decreased(P<0.01).Compared with the HS group,the mean arterial pressure of rats,LVPWd and LVmass in each group of Guizhi Decoction significantly decreased(P<0.05,P<0.01),myocardium Histopathological changes were alleviated,myocardial cell apoptosis rate decreased(P<0.05,P<0.01),the number of 8-OHdG positive cells in myocardial tissue significantly decreased(P<0.01),and the expression levels of Bax and cleaved caspase-3 protein significantly decreased(P<0.01).Bcl-2 and MnSOD protein expression levels significantly increased(P<0.01).Among them,Guishao 1∶1 group has more obvious improvement than Guishao 1∶2 group and Guishao 2∶1 group.Conclusion:Guizhi Decoction can effectively inhibit oxidative stress and cardiomyocyte apoptosis in salt-sensitive rats.The mechanism may be related to enhancing the expression of antioxidant enzymes and regulating apoptosis-related proteins.The Guizhi Decoction Guishao 1∶1 group has the best effect in reducing oxidative stress and inhibiting myocardial cell apoptosis.