芪苈强心胶囊多目标优化组合物对实验性心衰大鼠心功能的保护作用

The Protective Effects of Qili Qiangxin Capsule Composition Optimized by Multi-objective methods on Cardiac Function of Rats Suffered with Experimental Heart Failure

目的采用基于LARS算法的非线性多元回归方法预测最优变量组合,验证该组合的有效性,并进一步探讨芪苈强心胶囊对实验性心衰大鼠心功能保护的作用机制。方法 72只Sprague Dawley(SD)大鼠随机分为6组,假手术组,模型对照组,阳性对照组,芪苈强心胶囊组合物(QLQX)低、中、高剂量组,连续7次给药后,结扎冠状动脉复制实验性心衰模型,4 h后经右颈总动脉行左心室插管,测定左心室压峰值(LVP)等心功能指标;取血清测定超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH);取心肌组织Western Blot检测过氧化物酶体增殖物激活受体(PPAR)γ的表达。结果与模型对照组比较,QLQX可提高左心室压力(LVP)(P<0.05)、左心室内压最大上升速率(+LVdp/dtmax)(P<0.05),降低左心室舒张末期压(LVEDP)(P<0.05);还可提高SOD、GSH活性,降低MDA含量,QLQX高剂量降低幅度达20%(P<0.01);Western Blot检测出QLQX的PPARγ表达增高,以高剂量作用显著。结论采用LARS算法得到的芪苈强心胶囊最佳配伍对实验性心衰大鼠心功能有改善作用,其作用与清除自由基、提高心肌细胞抗氧化能力有关。

Objective To verify the validity of the combination optimized with nonlinear multiple regression method based on LARS algorithm and explore its protective mechanism on cardiac function of rats suffered with experimental heart failure. Methods Seventy-two SD rats were randomly divided into six groups： sham operation group, model group, Digoxin group, low, medium and high dose Qili Qiangxin Capsule optimal composition（QLQX） groups. After preventive treatment with the corresponding drugs for 7 times, the experimental heart failure model was developed with coronary artery ligation. Four hours after the surgery, peak left ventricular pressure （LVP） and other cardiac function were detected by cannulation to the left ventricular through right common carotid artery. The serum was separated to measure superoxide dismutase（SOD ）, malondialdehyde （MDA）, and glutathione（GSH）. And the total protein of cardiac muscle was extracted to observe the expression of peroxisome proliferator-activated receptor（ PPAR ） γ with Western blott. Results Compared with the model group, QLQX could increase LVP and ＋ LVdp/dtmax （P 〈 0.05 ）, decrease left ventricular end-diastolic pressure （LVEDP） （P 〈0.05） , also increase SOD and GSH activity, and decrease MDA eontent（P 〈 0.01）. Especially MDA was reduced by 20 % at high dose of QLQX group. The PPARγ expression was increased significantly in QLQX groups, in particular in high dose QLQX group. Conclusion The combination of QLQX Capsule could improve cardiac function of the rats suffered with experimental heart failure, and the mechanism may be related with the elimination of free radicals and with the increase of anti- oxidative capacity of myocardial cells.