参附注射液对脓毒症大鼠心肌氧化应激和线粒体呼吸功能的影响

目的:观察参附注射液对脓毒症大鼠心肌氧化应激和线粒体呼吸功能的影响。方法:采用肓肠结扎穿孔法制备腹腔感染脓毒症动物模型。80只SD大鼠随机分为假手术组(Sham),脓毒症组(CLP),参附注射液低、高剂量治疗组(LSF,HSF)共4组。记录手术后6、18h各组的平均动脉压(MAP)、心率(HR)、心脏收缩功能指标(LVDP和+dP/dt)、心脏舒张功能指标(LVEDP和-dP/dt)、心肌细胞凋亡发生率(AI)、心脏组织丙二醛(MDA)含量、超氧化物歧化酶(SOD)活性、呼吸控制比(RCR)。结果:与Sham组比较,CLP组术后6h的HR显著升高(P0.05),但术后18h的HR显著降低(P0.01);术后6h和18h的MAP、LVDP、+dP/dt、LVEDP、-dP/dt、SOD、RCR均显著下降(均P0.01),AI、MDA均显著升高(P0.05或0.01)。而与CLP组比较,LSF组术后6h的MAP和HR、HSF组术后6h的HR均无显著差异(均P0.05),但HSF组术后6h的MAP及LSF组和HSF组术后18h的HR、MAP均显著升高(P0.05或0.01);LSF组和HSF组术后6h、18h的LVDP、+dP/dt、LVEDP、-dP/dt、SOD、RCR均显著升高(P0.05或0.01);LSF组和HSF组术后6h、18h的AI、MDA均显著降低(P0.05或0.01)。结论:参附注射液可不同程度地增高CLP大鼠的平均动脉压、改善其心功能、减少心肌细胞凋亡的发生和心肌组织MDA含量,增加SOD活性,保护线粒体功能;且高浓度参附注射液则以上结果更明显。参附注射液有助于脓毒症大鼠心肌氧化应激和线粒体呼吸功能异常的恢复,这些作用的强度与参附注射液的剂量成正比。

Effects of Shenfu Injection on Myocardial Oxidative Stress and Mitochondrial Respiratory Function in Rats with Sepsis

Objective:To observe the effects of Shenfu Injection on myocardial oxidative stress and mitochondrial respiratory function in rats with sepsis.Methods:A total of 80 Sprague-Dawley(SD)rats were subjected to sepsis by cecal ligation and puncture(CLP),then they were randomly divided into four groups:sham operation group(n=20),sepsis group(n=20),Low-SF group(n=20)and High-SF group(n=20).Mean arterial pressure(MAP),heare rate(HR),heart systolic functional parameters(LVDP and +dP/dt),heart diastolic functional parameters(LVEDP and-dP/dt),apoptosis incidence of myocardial cells(AI),heart tissue malondialdehyde(MDA)content,superoxide dismutase(SOD)activity and respiratory control ratio(RCR)of each group were recorded 6 and 18h after the surgery.Results:Compared with sham group,HR in CLP group increased significantly 6h after surgery(P<0.05),but decreased significantly 18h after surgery(P<0.01).Compared with sham group,MAP,LVDP,+dP/dt,LVEDP,-dP/dt,SOD and RCR in CLP group all decreased significantly 6 and 18h after surgery(P<0.01),AI and MDA increased significantly 6 and 18h after surgery(P<0.05 or 0.01).Compared with CLP group,no significant differences were found in MAP and HR of LSF group 6h after surgery,and also in HR of HSF group 6h after surgery(P>0.05).Compared with CLP group,MAP in HSF group 6h after surgery,HR and MAP in both LSF and HSF group all increased significantly 18h after surgery(P<0.05 or 0.01).Compared with CLP group,LVDP,+dP/dt,LVEDP,-dP/dt,SOD and RCR in both LSF and HSF group increased significantly(P<0.05 or 0.01)6h and 18h after surgery.Compared with CLP group,AI and MDA in both LSF and HSF group decreased significantly(P<0.05 or P<0.01).Conclusion:Shenfu Injection can increase the mean arterial pressure to different extent in septic rats.In addition,Shenfu Injection can improve heart function,decrease myocardial apoptosis,reduce myocardial MDA content,enhance SOD activity and protect mitochondrial function.These results are more obvious in the group of high dose of Shenfu Injection.Shenfu Injection can be helpful to recover myocardial oxidative stress and mitochonodrial respiratory dysfunction in rats with sepsis.These effects are proportional to the dose of Shenfu Injection.