米诺环素预处理对大鼠心肌缺血再灌注损伤和HMGB1表达的影响

Influence of minocycline preconditioning on myocardial ischemia and reperfusion injury and HMGB1 expression in rats

目的:探讨米诺环素预处理对大鼠心肌缺血再灌注损伤的保护作用及其可能的机制。方法:成年雄性SD大鼠缺血前1h给予米诺环素(45mg/kg,ip),结扎冠脉前降支缺血30min后,恢复灌注4h;应用2,3,5-氯化三苯基四氮(TTC)法检测心肌梗死面积;试剂盒检测乳酸脱氢酶(LDH)、肌酸激酶(CK)、丙二醛(MDA)和超氧化物歧化酶(SOD);采用原位脱氧糖核苷酸末端转移酶介导的缺口末端标记(TUNEL)法检测心肌细胞的凋亡;Western blot检测高迁移率族蛋B1(HMGB1)表达。结果:与对照组相比,米诺环素预处理显著减小了心肌梗死面积,降低了心肌细胞凋亡和LDH、CK等血清心肌坏死标记物的表达(P<0.05)。米诺环素预处理也显著降低了MDA的表达,抑制了SOD的减少(P<0.05)。同时,米诺环素预处理抑制了缺血再灌注引起的HMGB1的表达(P<0.05)。结论:米诺环素预处理能够减轻心肌缺血再灌注损伤并抑制心肌细胞凋亡,这种保护作用可能与其抑制缺血再灌注诱导的HMGB1的表达有关。

Objective： To investigate the protection role of minocycline and the mechanism by which minocycline protects rats against myocardial ischemia and reperfusion（I/R） injury in rats.Methods： Anesthetized male rats were treated with minocycline（45 mg/kg,i.p.） 1 h before ischemia,and then subjected to ischemia for 30 min followed by reperfusion for 4 h.The lactate dehydrogenase（LDH）,creatine kinase（CK）,malondialdehyde（MDA） and superoxide dismutase（SOD） were measured.Infarct size was measured by TTC and the myocardial tissue apoptosis was assessed by TUNNEL assay.HMGB1 expression was assessed by Western blot.Results： Comparing with the control group,minocycline could significantly decrease the infarct size,myocardium apoptosis and the levels of LDH and CK（all P0.05）.Minocycline could also significantly inhibit the increase in the MDA level and the decrease in the SOD level（both P0.05）.Meanwhile,minocycline could also significantly inhibit the HMGB1 expression during myocardial I/R.Conclusions： Minocycline precondtioning could reduce myocardial ischemia and reperfusion injury and myocardial tissue apoptosis by inhibiting HMGB1 expression.