HMGB1减弱丹参酮ⅡA对大鼠心肌缺血/再灌注损伤的缓解作用

HMGB1 attenuates the mitigative effect to myocardial ischemia-reperfusion injury by tanshinoneⅡA in rats

目的研究外源性高迁移率族蛋白B1(HMGB1)对丹参酮ⅡA(TSA)缓解大鼠心肌缺血/再灌注(I/R)损伤的影响。方法将大鼠分为假手术(sham)组、I/R组(结扎前降支冠脉)、TSA组(I/R+静脉注射TSA 10 mg/kg)、TSA+HMGB1组(I/R+静脉注射TSA 10 mg/kg+腹腔注射重组HMGB1100μg/kg)。再灌注24 h后,用ELISA测定肌酸激酶同工酶(CK-MB)、TCC测心梗面积,RT-qPCR及Western blot测定炎性指标表达。结果I/R组与sham组比较,CK-MB升高(P<0.01),心肌梗死面积增大,白介素-6(IL-6)、白介素-1β(IL-1β)和肿瘤坏死因子-α(TNF-α)的转录水平增加(均P<0.01),HMGB1、NOD样受体蛋白3(NLRP3)和胱冬肽酶-1(caspase-1)表达增加(均P<0.05);TSA组与I/R组比较,CK-MB下降(P<0.01),心梗面积缩小(P<0.01),IL-6、IL-1β和TNF-α的转录水平下降(均P<0.05),HMGB1、NLRP3、caspase-1和核因子-κB(NF-κB)表达减少(均P<0.01);而TSA+HMGB1组与TSA组比较,CK-MB升高(P<0.01),心肌梗死面积增大(P<0.01),IL-6、IL-1β和TNF-α转录水平增加(均P<0.01),HMGB1、NLRP3、caspase-1和NF-κB表达增加(均P<0.05)。结论外源性HMGB1通过上调炎性因子表达减弱TSA缓解大鼠的心肌I/R损伤。

Objective To study the influence of exogenous high-mobility group box 1(HMGB1)on the mitigative effect of tanshinoneⅡA(TSA)to myocardial ischemia-reperfusion(I/R)injury.Methods Rats were divided into sham,I/R(ligation of left anterior descending coronary artery),TSA(I/R+TSA intravenous injection)and TSA+HMGB1(I/R+TSA intravenous injection+recombination HMGB1 intraperitoneal injection)groups.Serum CK-MB was measured by ELISA.Myocardial infarct area was measured by TCC.The expression of inflammatory indicators were measured by RT-qPCR and Western blot.Results Compared with sham group,CK-MB,myocardial infarct area,transcription level of IL-6,IL-1βand TNF-α,expression of HMGB1,NLRP3 and caspase-1 all increased in I/R group(P<0.05).Compared with I/R group,CK-MB,myocardial infarct area,transcription levels of IL-6,IL-1βand TNF-α,expressions of HMGB1,NLRP3,caspase-1 and NF-κB decreased in TSA group(P<0.05).However,compared with TSA group,CK-MB,myocardial infarct area,transcription levels of IL-6,IL-1βand TNF-α,expressions of HMGB1,NLRP3,caspase-1 and NF-κB increased in TSA+HMGB1 group(P<0.05).Conclusions Exogenous HMGB1 attenuates the mitigative effect of tanshinoneⅡA to rat myocardial I/R injury through up-regulation the expressions of inflammatory factors.