益气活血方对慢性心力衰竭大鼠心室重构的干预作用及其机制

目的:观察益气活血方对慢性心力衰竭模型大鼠心脏结构变化的影响,并从线粒体动力学和分泌型糖蛋白(Wnt)/β-链蛋白(β-catenin)通路探讨其作用机制。方法:40只雄性SD大鼠随机选取10只为假手术组,其余行左冠状动脉前降支结扎术构建慢性心力衰竭(CHF)大鼠模型,造模完成后随机分为模型组、卡托普利组和益气活血组,每组10只。给药组分别予以卡托普利片13.5 mg·kg^-1·d^-1,益气活血颗粒20 g·kg^-1·d^-1灌胃给药,干预8周后取心脏组织,称取体质量与心脏质量结合超声心动图检测心脏结构变化情况,行马松(Masson)染色测定心肌间质胶原容积分数,应用蛋白免疫印迹法(Western blot)检测心肌线粒体融合蛋白视神经萎缩相关蛋白1(Opa1),分裂蛋白线粒体动力相关蛋白1(Drp1)的表达水平,应用实时荧光定量聚合酶链式反应(Real-time PCR)检测Wnt/β-catenin通路相关因子低密度脂蛋白受体相关蛋白6(LRP6),糖原合成酶激酶-3β(GSK-3β),β-catenin mRNA的表达。结果:与假手术组比较,模型组左心室壁明显增厚(P<0.05),心腔明显扩大、心肌间质胶原含量升高(P<0.01);Opal表达水平降低,Drp1表达水平升高(P<0.01),LRP6,GSK-3β,β-catenin的mRNA表达量升高(P<0.01)。与模型组比较,益气活血组可减轻室壁增厚和心腔扩大(P<0.05,P<0.01),降低心肌间质胶原含量(P<0.05);上调Opa1的低表达、下调Drpl的高表达、下调LRP6,GSK-3β,β-catenin的高表达(P<0.01),作用效果优于或不劣于卡托普利组。结论:益气活血方可有效减轻慢性心力衰竭大鼠心室重构、改善线粒体能量代谢,其机制可能与抑制Wnt/β-catenin的相关因子的表达相关。

Effect of Reinforcing Qi and Activating Blood Recipe on Ventricular Remodeling in Rats with Chronic Heart Failure and Mechanisms Involved

Objective:To observe the intervention effect of Yiqi Huoxue recipe(YQHX)on ventricular remodeling in rats with chronic heart failure,in order to explore its mechanism.Method:Among 40 male SD rats,10 were randomly selected as the sham operation group.The left anterior descending coronary artery ligation was performed to construct the chronic heart failure(CHF)rat model.After modeling,they were randomly divided into model group,captopril group(13.5 mg·kg^-1·d^-1)and YQHX group(20 g·kg^-1·d^-1),and orally given the corresponding drugs.After 8 weeks of intervention,cardiac tissues were collected,body mass and heart mass were weighed,and echocardiography were performed to detect the changes in cardiac structure.Masson staining was performed to determine the myocardial interstitial collagen volume fraction.Western blot was used to detect the expression levels of mitochondrial fusion protein optic atrophy 1(Opa1)and cleavage protein dynamic-related protein 1(Drpl).The quantitative real-time fluorescence polymerase chain reaction(Real-time PCR)was applied to detect the expressions of Wnt/β-catenin pathway-related factors such as lipoprotein receptor-related protein 6(LRP6),glycogen synthase kinase-3β(GSK-3β)andβ-catenin.Result:Compared with the sham group,the left ventricular wall of the model group was significantly thickened(P<0.05),the cardiac cavity was significantly enlarged,and the content of collagen in the myocardial interstitium was increased(P<0.01).The expression level of Opal decreased,the expression level of Drp1 increased(P<0.05),the mRNA expression level of LRP6,GSK-3,andβ-catenin increased(P<0.01).Compared with the model group,YQHX group can reduce ventricular wall thickening,heart chamber enlargement,myocardial interstitial collagen content,up-regulate the low expression of Opa1,but down-regulate the high expressions of Drpl,LRP6,GSK-3β,β-catenin(P<0.05,P<0.01).Conclusion:YQHX can effectively alleviate ventricular remodeling and improve mitochondrial energy metabolism in rats with CHF.The mechanism may be related to the inhibition of Wnt/β-catenin related factors.