摘要
目的:观察酸枣叶总黄酮(FZSL)对大鼠缺血/再灌注(I/R)损伤心肌的影响,并探讨该作用是否由其调节低氧诱导因子1α(HIF-1α)的表达所介导。方法:60只Wistar大鼠随机分为6组:假手术(sham)组,I/R组,低、中、高剂量(50、100和200 mg/kg)FZSL组,以及HIF-1α抑制剂YC-1(20 mg/kg)+FZSL(200 mg/kg)组,每组10只。结扎大鼠冠状动脉左前降支,缺血30 min后再灌注3 h制备大鼠心肌I/R模型。采用TTC染色法测定大鼠心肌缺血面积和梗死面积;化学比色法检测大鼠血清肌酸激酶(CK)和乳酸脱氢酶(LDH)及心肌组织超氧化物歧化酶(SOD)的活性;ELISA法检测血清IL-1β、IL-6和TNF-α及心肌组织丙二醛(MDA)的含量;酶活性检测法测定心肌组织cas⁃pase-3的活性;Westernblot检测心肌组织HIF-1α蛋白表达。结果:与sham组相比,I/R组大鼠心肌发生显著梗死,血清LDH和CK活性,血清IL-1β、IL-6和TNF-α含量,以及心肌组织MDA含量和caspase-3活性均显著增加(P<0.01),而心肌组织SOD活性显著降低(P<0.01),同时心肌组织HIF-1α蛋白表达增加(P<0.01)。与I/R组相比,中、高剂量FZSL组大鼠心肌损伤程度显著减轻(P<0.01),而心肌组织HIF-1α蛋白表达显著增加(P<0.05)。用YC-1抑制HIF-1α后,FZSL的心肌保护效应显著减弱(P<0.01)。结论:FZSL可以减轻大鼠心肌I/R损伤,其机制可能与上调HIF-1α的表达有关。
AIM:To observe the effect of total flavonoids from Ziziphus jujuba var.spinosa leaves(FZSL)on myocardial ischemia/reperfusion(I/R)injury,and to explore whether their effect is mediated by the regulation of hypoxia-inducible factor-1α(HIF-1α)expression.METHODS:Sixty Wistar rats were randomly divided into 6 groups:sham group,I/R group,low-,medium-and high-dose(50,100 and 200 mg/kg)FZSL groups,and HIF-1αinhibitor YC-1(20 mg/kg)+FZSL(200 mg/kg)group,with 10 rats in each group.The model of myocardial I/R was established by ligating the left anterior descending coronary artery for 30 min with subsequent reperfusion for 3 h.The ischemic and infarct areas were measured by TTC staining.The activity of creatine kinase(CK)and lactate dehydrogenase(LDH)in serum,and the activity of superoxide dismutase(SOD)in myocardial tissue were detected by chemical colorimetry.The levels of IL-1β,IL-6 and TNF-αin serum and malondialdehyde(MDA)in myocardial tissue were measured by ELISA.Caspase-3 activity in myocardial tissue was determined by enzyme activity assay.The expression of HIF-1αprotein in myocardial tissue was detected by Western blot.RESULTS:Compared with sham group,myocardial infarction was observed in I/R group.The serum LDH and CK activity,serum IL-1β,IL-6 and TNF-αlevels,and myocardial MDA content and caspase-3 activity were significantly increased(P<0.01).The activity of SOD in myocardial tissue was decreased significantly(P<0.01).The expression of HIF-1αprotein in myocardial tissue was increased(P<0.01).Compared with I/R group,the degree of myocardial injury in medium-and high-dose FZSL groups was decreased significantly(P<0.01),while the expression of HIF-1αprotein in myocardial tissue was increased significantly(P<0.05).YC-1,a inhibitor of HIF-1α,blocked the pro-tective effect of FZSL significantly(P<0.01).CONCLUSION:Treatment with FZSL attenuates myocardial I/R injury in rats,which may be related to up-regulation of HIF-1αexpression.
作者
赵焕新
杨蓉
翟晓艳
杨李旺
季新燕
王惠洁
ZHAO Huan-xin;YANG Rong;ZHAI Xiao-yan;YANG Li-wang;JI Xin-yan;WANG Hui-jie(School of Basic Medical Sciences,Shanxi University of Chinese Medicine,Taiyuan 030024,China)
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2022年第8期1384-1389,共6页
Chinese Journal of Pathophysiology
基金
山西中医药大学科技创新能力培育计划(No.2019PY-133)。
关键词
酸枣叶总黄酮
低氧诱导因子1Α
心肌缺血
再灌注损伤
Total flavonoids from Ziziphus jujuba var.spinosa leaves
Hypoxia-inducible factor-1α
Myocar⁃dial ischemia
Reperfusion injury
