参附注射液对心力衰竭大鼠氧化应激及细胞凋亡的影响

摘要

目的 观察参附注射液对心力衰竭大鼠氧化应激及细胞凋亡的影响并探讨其机制.方法 将36只SD大鼠随机分为假手术组(12只)、心衰模型组(12只)、参附治疗组(12只),术后第4周开始给予参附治疗组每日1次灌胃给药[日剂量6.0 mL/(kg·d)],共4周.观察评定左室舒张末径(LVDS)、室收缩末径(LVDd)、左室射血分数(LVEF)、短轴缩短率(Fs)、血流动力学指标心率(HR)、左心室收缩压(LVSP)、左室舒张末期压(LVEDP)、左心室压变化速率最大值、心肌超氧化物歧化酶(SOD)含量、心肌丙二醛(MAD)含量及心肌目的蛋白质等的变化.结果 与假手术组比较,模型组LVDd、LVDS明显增大,LVEF、FS明显下降,BNP水平明显升高(均P＜ 0.05);参附注射液治疗后与模型组比较,各指标均改善(均P＜ 0.05).与假手术组比较,模型组LVEDP明显增大,LVSP下降,+dp/dtmax、-dp/dtmax、HR明显下降(均P＜0.01);参附注射液治疗后与模型组比较,各指标均改善(均P＜0.01).与假手术组比较,心衰模型组心肌SOD活性明显降低(P＜0.01),给予参附注射液处理后,心肌SOD活性明显高于心衰模型组(P＜0.01);心衰模型组MDA含量明显高于假手术组(P＜0.01),参附注射液处理后,MDA含量明显低于心衰模型组(P＜0.01).Bax蛋白表达明显降低,Bcl-2蛋白表达明显升高,Bax/Bcl-2的比值明显降低(P＜0.01).SOD与Bcl-2/Bax线性相关性具有统计学意义(r=0.652,P＜ 0.001),存在线性正相关关系;MDA与Bcl-2/Bax线性具有统计学意义(r=-0.644,P＜ 0.001),存在线性负相关关系.结论 参附注射液可降低氧化应激水平,抑制蛋白凋亡,从而改善心衰大鼠心功能,其机制可能与上调凋亡抑制蛋白Bcl-2,下调促凋亡蛋白Bax的表达有关.%Objective:To investigate the effects of Shenfu Injection on oxidative stress and apoptosis in rats with heart failure.Methods:36 SD rats were randomly divided into three groups with 12 rats in each:the sham operation group,the heart failure model group and Shenfu treatment group.4 weeks after operation,the treatment group was given intragastric administration once a day daily dose:6.0 mL/(kg· d),for 4 weeks.The following data was detected:LVDS,LVDd,LVEF,FS,HR,LVSP,LVEDP,maximum rate of LVP,the content of the SOD and MAD and cardiac target protein.Results:Compared with the sham operation group,LVDd and LVDS of the model group increased obviously;LVEF and FS decreased obviously,and the level of BNP increased obviously (P ＜ 0.05).Compared with the model group,the indexes recovered after treatment of Shenfu Injection(P＜ 0.05).Compared with the sham operation group,LVEDP of the model group increased obviously;LVSP decreased,and +dp/ dt,Max,-dp/dt,Max and HR decreased obviously (P＜0.01).Compared with the model group,the indexes recovered after treatment of Shenfu Injection(P＜ 0.01).Compared with the sham operation group,the activity of SOD in the heart failure model group decreased obviously (P＜ 0.01).After treated with Shenfu Injection,the myocardial SOD activity was significantly higher than that in the heart failure model group (P＜ 0.01).The content of MDA in heart failure model group was significantly higher than that in sham operated group (P ＜ 0.01).The content of MDA after the treatment of Shenfu Injection was lower than that in heart failure model group (P＜ 0.01).The expression of Bax protein was significantly decreased;the expression of Bcl-2 protein increased significantly,and the ratio of Bax/Bcl-2 decreased significantly(P＜ 0.01).The linear correlation between SOD and Bcl-2/Bax was statistically significant (r =0.652,P＜ 0.001),and linear positive correlation existed.Linearity of MDA and Bcl-2/Bax was statistically significant (r =-0.644,P＜ 0.001),and linear negative correlation exists.Conclusion:Shenfu injection can decrease the level of oxidative stress,inhibit protein apoptosis,and thus improve cardiac function in heart failure rats and the mechanism may be related to the up-regulation of apoptosis inhibitory protein Bcl-2 and down-regulation of Pro apoptotic protein Bax.