中国中西医结合杂志2024，Vol.44Issue(12)：1462-1470,9.DOI:10.7661/j.cjim.20241030.112
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
摘要
Abstract
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 neurons in the hippocampal region,lower cell density,and damaged nuclei.However,the intervention groups showed reduced myocardial and hippocampal damage compared with the AMI+CUMS group.Compared with the SO group,the SO+CUMS group had lower levels of NOR,5-HT,and DA in brain tissue(P＜0.05,P＜0.01).The AMI group showed decreased ejection fraction(EF),cardiac output(CO)(P＜0.01).Compared with AMI group,the AMI+CUMS group showed decreased EF,CO,NOR,5-HT,and DA levels(P＜0.05,P＜0.01).Compared with the AMI+CUMS group,the WM group showed increased EF,NOR and 5-HT in brain tissue,decreased myocardial Beclin-1(P＜0.05,P＜0.01).The high-dose JWSQP group showed increased EF,CO,NOR,5-HT,DA in brain tissue,myocardial p-AKT,p-MTOR,and decreased myocardial Beclin-1(P＜0.05,P＜0.01).Conclusions JWSQP Powder regulates the expression of autophagy-related proteins by inhibiting the PI3K-Akt-mTOR signaling pathway and improves cardiac function and stress state.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Key words
acute myocardial infarction/psychological stress response/chronic unpredictable mild stress/autophagy/PI3K-Akt-mTOR signaling pathway/Jiwei Shenqipo Powder/Chinese herbal compound/integrative medicine引用本文复制引用
徐嘉唯,刘剑刚,陈露莹,蒋跃绒,张京春..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[J].中国中西医结合杂志,2024,44(12):1462-1470,9.基金项目
中国中医科学院科技创新工程重大攻关项目(No.CI2021A00908) （No.CI2021A00908）
全国中医临床优秀人才项目(No.国中医药人教函[2022]1号) （No.国中医药人教函[2022]1号）
中国中医科学院西苑医院能力提升项目(No.XYZX0101-14) （No.XYZX0101-14）
