芪参胶囊对陈旧性心肌梗死大鼠的心肌保护作用及机制研究  

Cardioprotective Efficacy of Qishen Capsule in Rats with Chronic Myocardial Infarction

作　　者：马杰[1] 郭彩霞[1] 陆培培[1] 梁晓鹏[1] 樊栓成 马丽红[1] 

机构地区：[1]中国医学科学院北京协和医学院阜外医院,北京100037 [2]上海凯宝药业股份有限公司,上海201419

出　　处：《中国药学杂志》2017年第13期1137-1146,共10页Chinese Pharmaceutical Journal

基　　金：国家自然科学基金资助项目(81071177)

摘　　要：目的探讨芪参胶囊(Qishen capsule,QSC)对陈旧性心肌梗死大鼠的心肌保护作用及相关的作用机制。方法前降支结扎法制备大鼠心肌梗死模型,分为以下3组:(1)陈旧性心肌梗死模型组(MI)(n=14),生理盐水灌胃;(2)低剂量对照组(MI+QSCL)(n=14),低剂量芪参胶囊混悬液灌胃治疗,5×10~4mg·kg^(-1)·d^(-1),持续4周;(3)治疗组(MI+QSC)(n=14),常规剂量芪参胶囊混悬液灌胃治疗,10×10~4mg·kg^(-1)·d^(-1),持续4周。Sham组,单纯开胸,冠状动脉左前降支出穿线不行结扎(n=16),其中又分为:(1)Sham组(n=8):生理盐水灌胃;(2)Sham+QSC组(n=8):芪参胶囊混悬液灌胃治疗,10×10~4mg·kg^(-1)·d^(-1),持续4周。超声心动评价大鼠心功能,病理学方法计数毛细血管及小动脉的密度并用免疫印迹法(Western blot)评价心肌细胞凋亡和血管新生情况。结果常规剂量芪参胶囊治疗后可有效改善心功能。与模型组相比,其左心室射血分数(LVEF)[(44.93±5.66)vs(57.21±8.4)]与左室短轴缩短率(LVFS)[(19.79±3.01)vs(26.89±5.64)]显著升高,左心室舒张末期内径(LVEDD)与左心室收缩末期内径(LVEDS)明显降低(P<0.05);MI+QSC组的LVEDP[(15.00±2.63)vs(20.78±2.35)]与dp/dtmax[(3 346.11±202.17)vs(3 634.03±286.56)]明显增高。常规剂量芪参胶囊明显抑制心肌细胞的凋亡。与模型组和低剂量组(5×10~4mg·kg^(-1)·d^(-1))相比,常规剂量(10×10~4mg·kg^(-1)·d^(-1))芪参胶囊组梗死面积及梗死瘢痕明显减少,活性caspase-3、Bax、cytochrome C的表达量明显降低,而Bcl-2的表达量明显增加,且Bcl-2/Bax的比值也明显增加。(3)QSC的干预治疗能够促进心肌梗死后大鼠的血管新生。常规剂量(10×10~4mg·kg^(-1)·d^(-1))芪参胶囊组增加了梗死区平滑肌激动蛋白和CD31阳性的血管密度,明显提高了血管新生水平。分别使用ELISA与实时定量PCR的方法检测了血管内皮生长因子(VEGF)蛋白水平与mRNA水平的表达情况,发现常规剂量芪参胶囊组(10×10OBJECTIVE To explore whether QSC can have cardioprotective efficacy after myocardial infarction（MI） ,we design this experiment in a preclinical model of myocardial infarction in rats. METHODS Four weeks after left anterior descending coronary artery ligation, rats received either intragastric administration of QSC, or the same volume of saline. Male SD rats were given the ligation of anterior descending coronary artery. After 4 weeks,42 male rats were chosen and randomly divided into 3 groups. The model group（ normal saline solution for 4w, n = 14 ） , low-dose control group（ 5×10^4mg·kg·d^-1 of drug QSC, for 4w, n = 14） , and QSC moderate dose group（ 10×10^4mg·kg·d^-1 of Qsc for 4w,n = 14）. The sham-operation group（ n = 16） was only given treatment of chest-open without ligation of anterior descending coronary artery, divided into 2 groups, the Sham-group （normal saline solution for 4w, n = 8 ）and Sham ＋ QSC group （5 ×10^4mg·kg·d^-1 of drug Qsc, for 4w, n = 8）. Cardiac function was assessed echo cardio-graphically. Angiogenesis and apoptosis were detected using histology and Western blot methods four weeks after QSC therapy. RESULTS Reductions in infarction area and scar collagen content in MI ＋ QSC group were observed in the infarct region compared with the saline control and MI ＋ QSCL group. QSC also improved cardiac function after treatment. QSC significantly decreased apoptosis relative to control group, evidenced by influencing the expression of Bcl-2, Bax, cytochrom C and caspase-3 in the myocardial infarction. Meanwhile, angiogenesis in the infarctive regions were significantly enhanced relative to control group, evidenced by increased density of a-smooth muscle actin and CD31 positive vessels respectively. Similarly, the mRNA expressions of VEGF and HIF-1α were up-regulated. Additionally. OSC involvement also increased the phosphorylation of AKT and down-regulated the phosphorylation of MEK/ERK. CONCLUSION There is no significant difference between QSC low-dose

关 键 词：芪参胶囊 血管新生 细胞凋亡 

分 类 号：R965[医药卫生—药理学]