加味参七珀散调节PI3K/Akt/mTOR信号通路保护急性心肌梗死合并心理应激大鼠缺血心肌  

Jiawei Shenqipo Powder Protects Myocardium of Rats with Acute Myocardial Infarction Combined with Psychological Stress Via Regulating PI3K/Akt/mTOR Signaling Pathway

作　　者：徐嘉唯 刘剑刚[1] 陈露莹 蒋跃绒[1] 张京春[1] XU Jia-wei;LIU Jian-gang;CHEN Lu-ying;JIANG Yue-rong;ZHANG Jing-chun(National Clinical Research Center for Chinese Medicine Cardiology,Xiyuan,Hospital,China Academy of Chinese Medical Sciences,Beijing,100091;Department of Integrated Traditional Chinese and Western Medicine,Xi'an Children's Hospital,xi'an,710000)

机构地区：[1]中国中医科学院西苑医院心血管病中心,国家中医心血管病临床医学研究中心,北京100091 [2]西安市儿童医院中西医结合科,西安710000

出　　处：《中国中西医结合杂志》2024年第12期1462-1470,共9页Chinese Journal of Integrated Traditional and Western Medicine

基　　金：中国中医科学院科技创新工程重大攻关项目(No.CI2021A00908);中国中医科学院西苑医院能力提升项目(No.XYZX0101-14);全国中医临床优秀人才项目(No.国中医药人教函[2022]1号)。

摘　　要：目的 基于磷脂酰肌醇-3-激酶(PI3K)/蛋白激酶B(AKT)和哺乳动物雷帕霉素蛋白(mTOR)通路观察加味参七珀散对急性心肌梗死(AMI)合并心理应激(PSR)模型大鼠心脏功能和脑组织神经递质的影响。方法 将110只Wistar大鼠随机分为假手术组(n=30)和造模组(n=80),造模组采用冠状动脉前降支结扎方法制作AMI模型,假手术组仅手术不结扎冠状动脉。将手术成功的假手术组大鼠20只随机分为假手术组和假手术+不可预知的应激反应(CUMS)组,将造模成功的造模组大鼠50只随机分为AMI组、AMI+CUMS组、西药组、七珀散小组、七珀散大组,每组均10只,CUMS组及干预组采用CUMS造模。西药组给予帕罗西汀1.8 mg/kg灌胃,七珀散大、小组分别给予生药2.40、1.20 g/kg灌胃,AMI组和AMI+CUMS组给予等容积溶液连续4周。各组大鼠行超声心动图检测;光学显微镜观察大脑海马区及心肌细胞的形态学变化;检测大鼠脑组织一氧化氮还原酶(NOR)、5-羟色胺(5-HT)和多巴胺(DA)含量;Western Blot检测心肌组织自噬相关蛋白自噬微管相关蛋白轻链3蛋白(LC3B-Ⅱ)、自噬效应蛋白(Beclin-1)、磷酸化PI3K(p-PI3K)、磷酸化m TOR(p-m TOR)表达。结果 假手术组及假手术+CUMS组大鼠的心肌及海马区域细胞排列整齐,轮廓完整;AMI组及AMI+CUMS组大鼠的心肌组织纹理错乱,细胞数目减少,出现大量炎症细胞浸润,海马区神经细胞数量减少,密度降低,细胞核损伤;与AMI+CUMS组比较,各干预组大鼠心肌细胞及海马区神经细胞损伤程度减轻。与假手术组比较,假手术+CUMS组大鼠脑组织NOR、5-HT、DA水平下降(P<0.05,P<0.01);AMI组大鼠射血分数(EF)、心输出量(CO)下降(P<0.01)。与AMI组比较,AMI+CUMS组大鼠EF、CO、脑组织NOR、5-HT、DA水平下降(P<0.05,P<0.01)。与AMI+CUMS组大鼠比较,西药组大鼠EF、脑组织NOR、5-HT水平升高,心肌Beclin-1表达降低(P<0.05,P<0.01);七珀散大组大鼠的EF、CO、脑组织NOR、5-Objective To observe the effects of Jiawei Shenqipo(JWSQP)Powder on cardiac function and brain tissue neurotransmitters in rats with acute myocardial infarction(AMI)combined with psychological stress response(PSR)based on the phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)and mammalian target of rapamycin(mTOR)pathways.Methods Totally 110 Wistar rats were randomly divided into the sham group(n=30)and the model group(n=80).The model group underwent AMI induction by left anterior descending coronary artery ligation,while the sham group underwent the same procedure without coronary ligation.The 20 successful operation rats in sham group were further randomly divided into a sham-operated(SO)group and a SO+chronic unpredictable mild stress(CUMS)group.The 50 successful modeling rats in model group were randomized into the AMI grou,AMI+CUMS group,Western medicine(WM)group,low-dose JWSQP group,and high-dose JWSQP group,10 rats in each group.PSR was induced by CUMS in rats in the CUMS and the intervention group.The WM group received 1.8 mg/kg paroxetine via gavage,while the low-and high-dose JWSQP groups were administered JWSQP powder at 2.40 g/kg and 1.20 g/kg,respectively.The AMI and AMI+CUMS groups were given an equal volume of solution for four consecutive weeks.The cardiac echocardiography were performed.Morphological changes of hippocampus and myocardial cells were observed by optical microscope.Levels of nitric oxide reductase(NOR),5-hydroxytryptamine(5-HT),and dopamine(DA)in the brain tissue were measured.The expression of autophagy-related proteins,including microtubule-associated protein 1 light chain 3 beta(LC3B-Ⅱ),Beclin-1,phosphorylated PI3K(p-PI3K),and phosphorylated mTOR(p-mTOR)in myocardial tissue were detected by Western Blot.Results The myocardial and hippocampal cells in the SO and SO+CUMS groups were arranged neatly with intact morphology.While the AMI and AMI+CUMS groups showed disorganized myocardial tissue,reduced cell count,extensive inflammatory infiltration,as well as reduced number of ne

关 键 词：急性心肌梗死 心理应激反应 慢性轻度不可预知的应激 细胞自噬 PI3K-Akt-mTOR信号通路 加味参七珀散 中药复方 中西医结合 

分 类 号：R285.5[医药卫生—中药学]