北京中医药大学学报2025，Vol.48Issue(6)：802-810,9.DOI:10.3969/j.issn.1006-2157.2025.06.010
理气活血滴丸通过调控HIF-1α/BNIP3信号通路抑制细胞凋亡改善大鼠心肌缺血再灌注损伤的机制
Liqi Huoxue Dripping Pill improves myocardial ischemia-reperfusion injury in rats by inhibiting apoptosis by regulating the HIF-1α/BNIP3 signaling pathway
摘要
Abstract
Objective To explore the mechanism by which Liqi Huoxue Dripping Pill(LQHXDP)inhibits cardiomyocyte apoptosis in rats with myocardial ischemia-reperfusion injury(MIRI).Methods Male Sprague-Dawley(n=96)rats were randomly assigned to a normal,sham-operated,model,LQHXDP,adenovirus negative control(Ad-shNC),adenovirus-mediated HIF-1α knockdown(Ad-shHIF-1α),LQHXDP+Ad-shNC,or LQHXDP+Ad-shHIF-1α group using a random number table.LQHXDP was administered daily via oral gavage at 175.0 mg/(kg·d)for 10 consecutive days.On day 7,recombinant adenovirus was injected into the left ventricular wall of rats in the corresponding groups at multiple points.On day 10,the MIRI model was established by ligating the left anterior descending coronary artery.The sham-operated group underwent thoracotomy and suture placement without coronary ligation.Samples were collected after reperfusion was completed.Serum creatine kinase isoenzymes(CK-MB),cardiac troponin I(cTnI),and heart-type fatty acid binding protein(H-FABP)levels were measured using enzyme-linked immunosorbent assay.2,3,5-Triphenyltetrazolium chloride staining was used to measure the volume ratio of myocardial infarction.HE staining was performed to observe the morphology of myocardial tissue.Terminal transferase uridyl nick end labeling assay was conducted to analyze the apoptosis rate of cardiomyocytes,and Western blotting was used to detect the expression of key proteins in the apoptosis(B-cell lymphoma-2[Bcl-2],Bcl-2 associated X protein[Bax],and cleaved cysteinyl aspartate specific proteinase 3[Cleaved-Caspase-3]and HIF-1α/Bcl-2-adenovirus E1B 19 kDa interacting protein 3(BNIP3)signaling pathway(HIF-1α,heme oxygenase-1[HO-1],and BNIP3).Results LQHXDP pretreatment significantly reduced serum CK-MB,cTnI,and H-FABP levels,as well as the myocardial infarction volume ratio in rats with MIRI.LQHXDP also improved myocardial tissue morphology,decreased cardiomyocyte apoptosis,upregulated Bcl-2 protein expression,and downregulated Bax,Cleaved-Caspase-3,HIF-1α,HO-1,and BNIP3 protein expressions(P<0.05).However,adenovirus-mediated shRNA HIF-1α impaired the effects of LQHXDP pretreatment in attenuating myocardial injury and inhibiting apoptosis in MIRI rats(P<0.05).Conclusion LQHXDP reduces cardiomyocyte apoptosis and protects rat myocardium from MIRI by regulating the HIF-1α/BNIP3 signaling pathway.关键词
理气活血滴丸/心肌缺血再灌注损伤/细胞凋亡/缺氧诱导因子-1α/B淋巴细胞瘤-2-腺病毒E1B 19 kDa相互作用蛋白3信号通路/大鼠Key words
Liqi Huoxue Dripping Pill/myocardial ischemia-reperfusion injury/apoptosis/hypoxia-inducible factor-1α/B-cell lymphoma-2-adenovirus E1B 19 kDa interacting protein 3 signaling pathway/rats分类
中医学引用本文复制引用
刘田静,陈向云,汤小芳,路雨昕,李尧锋..理气活血滴丸通过调控HIF-1α/BNIP3信号通路抑制细胞凋亡改善大鼠心肌缺血再灌注损伤的机制[J].北京中医药大学学报,2025,48(6):802-810,9.基金项目
国家自然科学基金项目(No.82360965,No.81860873)National Natural Science Foundation of China(Nos.82360965 and 81860873) （No.82360965,No.81860873）
