摘要
目的探究落新妇苷(AST)对大鼠心肌缺血再灌注损伤(MIRI)的影响,以及可能的作用机制。方法将SD雄性大鼠随机分为假手术组、模型组、阳性对照组(复方丹参片240 mg/kg)和AST低、高剂量组(30、90 mg/kg)以及AST高剂量+缺氧诱导因子1α(HIF-1α)抑制剂组(AST 90 mg/kg+2-甲氧基雌二醇15 mg/kg),每组25只。除假手术组外,其他各组大鼠均建立MIRI模型,灌胃或腹腔注射相应药物或生理盐水,连续28 d。测定各组大鼠血清中心肌肌钙蛋白I(cTnI)、肌酸激酶同工酶(CK-MB)含量,测量心肌梗死体积比,观察心肌组织病理形态变化、心肌细胞凋亡率和心肌组织线粒体的超微结构,测定心肌组织中肿瘤坏死因子α(TNF-α)、白细胞介素6(IL-6)、丙二醛(MDA)含量和超氧化物歧化酶(SOD)活性以及HIF-1α、腺病毒E1B相互作用蛋白3(BNIP3)、肌球蛋白样Bcl-2结合蛋白(Beclin1)的表达,并计算微管相关蛋白轻链3(LC3)Ⅱ与Ⅰ的比值(简称“LC3Ⅱ/Ⅰ”)。结果与模型组比较,阳性对照组和AST低、高剂量组大鼠的心肌组织无明显肿胀,心肌纤维排列整齐,心肌梗死体积比和c TnI、CK-MB、TNF-α、IL-6、MDA含量以及细胞凋亡率均显著降低(P<0.05),SOD活性和HIF-1α、BNIP3、Beclin1蛋白表达量以及LC3Ⅱ/Ⅰ均显著升高(P<0.05)。HIF-1α抑制剂可显著削弱AST对MIRI模型大鼠上述指标的改善作用(P<0.05)。结论AST可以通过激活HIF-1α/BNIP3信号通路来增强线粒体自噬,从而减轻大鼠MIRI。
OBJECTIVE To investigate the effects of astilbin(AST)on myocardial ischemia-reperfusion injury(MIRI)in rats and its potential mechanism.METHODS SD male rats were randomly divided into sham operation group,model group,positive control group(Compound Salvia miltiorrhiza tablets,240 mg/kg),AST low-dose and high-dose groups(30,90 mg/kg),and highdose of AST+hypoxia-inducible factor-1α(HIF-1α)inhibitor group(AST 90 mg/kg+2ME215 mg/kg),with 25 rats in each group.Except for sham operation group,MIRI model was induced in other groups,and then given relevant drug or normal saline intragastrically or intraperitoneally,for consecutive 28 d.Serum contents of cardiac troponin I(cTnI)and creatine kinase isoenzyme(CK-MB)were detected;volume ratio of myocardial infarction was measured;the pathological changes of myocardium,the apoptotic rate of myocardial cells and ultrastructure of mitochondria in myocardial tissue were all observed.The contents of tumor necrosis factorα(TNF-α),interleukin 6(IL-6)and malondialdehyde(MDA),the activity of superoxide dismutase(SOD),the expressions of HIF-1α,adenovirus E1B interacting protein 3(BNIP3)and myosin-like Bcl-2 interacting protein(Beclin1)were determined in myocardium.The ratio of microtubule-associated protein light chain 3(LC3)ⅡtoⅠ(LC3Ⅱ/Ⅰ)in rat myocardium was calculated.RESULTS Compared with model group,no obvious swelling was found in the myocardial tissue of rats in positive control group,AST low-dose and high-dose groups,and the myocardial fibers were arranged regularly;the volume ratio of myocardial infarction,the contents of cTnI,CK-MB,TNF-α,IL-6 and MDA,the apoptotic rate were decreased significantly(P<0.05),while SOD activity,protein expressions of HIF-1α,BNIP3 and Beclin1,LC3Ⅱ/Ⅰwere increased significantly(P<0.05).HIF-1αinhibitor could significantly weaken the improvement effect of AST on the above indicators in MIRI model rats(P<0.05).CONCLUSIONS AST enhances mitochondrial autophagy by activating HIF-1α/BNIP3 signaling pathway,thereby reducing MIRI in rats.
作者
陈兴华
韩露
贡鸣
张继倬
CHEN Xinghua;HAN Lu;GONG Ming;ZHANG Jizhuo(Dept.of Cardiac Surgery,Beijing Shijitan Hospital Affiliated to Capital Medical University,Beijing 100038,China;Medical Research Center,Beijing Chaoyang Hospital Affiliated to Capital Medical University,Beijing 100020,China;Dept.of Cardiac Surgery,Beijing Anzhen Hospital Affiliated to Capital Medical University,Beijing 100029,China)
出处
《中国药房》
CAS
北大核心
2023年第10期1193-1198,1203,共7页
China Pharmacy
基金
国家自然科学基金资助项目(No.81770466)。