时珍国医国药2025，Vol.36Issue(23)：4412-4420,9.DOI:10.70976/j.1008-0805.SZGYGY-2025-2302
理气化痰活血方调控MAMs介导的心肌细胞凋亡改善冠脉微循环障碍的机制
Mechanism of regulating MAMs-mediated cardiomyocyte apoptosis by Liqi Huatan Huoxue Formula(理气化痰活血方)to improve coronary microcirculatory disorders
摘要
Abstract
Objective To explore the effect of the medicinal serum containing Liqi Huatan Huoxue Formula(理气化痰活血方)regulat‐ing NRG-1 expression on mitochondria-associated endoplasmic reticulum membrane(MAMS)-mediated apoptosis of cardiomyocytes.Methods A rat primary cardiac microvascular endothelial cell-cardiomyocyte co-culture model was established,and randomly divided into blank group,control group,siRNA interference group,LHHF group,siRNA+LHHF group,nicorandil group and valsartan group,except for the blank group,the rest of the groups were subjected to H/R treatment,and after 72h of isolation and culture,the drug-containing serum was replaced and continued to be cultured for 36h,and the EdU method was used to Cell proliferation was detected,the expression of MAMS-related proteins Mfn2,PTPIP5,VDAC and VAPB was detected by Western-blot,and the relative mRNA expression levels of apoptotic factors and NRG-1/ErbB pathway-related genes were detected by qPCR.Results EdU results showed that compared with the model group,in the LHHF,nicorandil group,and valsartan group,the cell proliferation rate increased(P<0.05 or P<0.001).Westernblot(WB)results showed that compared with the model group,the protein expression level of Mfn2 in the LHHF group increased(P<0.01),and that the protein expression level of PTPIP5,VDAC,and VAPB decreased(P<0.05 or P<0.001).ELISA results showed that compared with the model group,the NRG-1 level was reduced in the siRNA interference group(P<0.001),and in the LHHF group,the nicorandil group,and the valsartan group,the NRG-1 level showed different degrees of elevation(P<0.001).qPCR results showed that compared with the model group,the LHHF group,the nicorandil group,and the valsartan group The qPCR results showed that compared with the model group,the relative expression levels of GRP78,CHOP and Caspase-12 were decreased(P<0.01 or P<0.001),and the relative expression levels of ErbB2,ErbB4,PI3K,AKT and GSK-3β mRNA were increased(P<0.01 or P<0.001).Conclusion LHHF can inhibit cardiomyocyte apoptosis and protect cardiomyocytes by regulating the expression of NRG-1 in cardiac microvascular endothelial cells induced by hypoxia and reoxygenation and regulating the homeostasis of MAMs.关键词
理气化痰活血方/心脏微血管内皮细胞/心肌细胞/细胞凋亡/线粒体相关内质网膜/NRG-1/缺氧损伤Key words
Liqi Huatan Huoxue Formula(理气化痰活血方)/Cardiac microvascular endothelial cells/Cardiomyocytes/Apop‐tosis/mitochondria-associated endoplasmic reticulum membrane/NRG-1/Hypoxia-reoxygenation injury分类
医药卫生引用本文复制引用
葛昭,苏立硕,任思霖,刘桐作,吴旭东,周梦雪,李默涵,王贤良..理气化痰活血方调控MAMs介导的心肌细胞凋亡改善冠脉微循环障碍的机制[J].时珍国医国药,2025,36(23):4412-4420,9.基金项目
国家自然科学基金面上项目(82174326) （82174326）
国家中医药管理局中医药创新团队及人才支持计划项目(ZYYCXTD-C-202203) （ZYYCXTD-C-202203）
国家教育部创新团队发展计划项目(IRT_16R54) （IRT_16R54）
