脂联素通过Nrf2/HO-1通路对急性心肌梗死大鼠心功能和心肌细胞凋亡的作用机制

Mechanism of Adiponectin on Cardiac Function and Myocardial Cell Apoptosis in Rats with Acute Myocardial Infarction through Nrf2/HO-1 Pathway

目的探讨脂联素(APN)通过核因子E2相关因子2(Nrf2)/血红素氧化酶1(HO-1)通路对急性心肌梗死(AMI)大鼠心功能和心肌细胞凋亡的作用。方法将健康成年雄性SD大鼠随机分为Sham组、AMI组、APN组和APN+锌原卟啉9(ZPP-Ⅸ)组,Sham组不做任何处理,AMI组、APN组和APN+ZPP-Ⅸ组均建立AMI模型,APN组给予腹腔注射APN,APN+ZPP-Ⅸ组给予腹腔注射APN+ZPP-Ⅸ。对比4组血清心肌酶含量、心肌中凋亡基因、心肌细胞凋亡率和Nrf2、HO-1表达水平。结果Sham组血清乳酸脱氢酶(LDH)、磷酸肌酸激酶同工酶(CK-MB)、磷酸肌酸激酶(CK)、心肌细胞凋亡率、心肌中Bcl-2相关X蛋白(Bax)、Nrf2、HO-1、Cleaved-caspase-3、Hb-1的表达水平明显低于AMI组,差异均有统计学意义(P<0.05);Sham组的心肌中B淋巴细胞瘤2蛋白(Bcl-2)表达水平明显高于AMI组,差异有统计学意义(P<0.05);AMI组LDH、CK-MB、CK、心肌细胞凋亡率、心肌中Bax和Cleaved-caspase表达水平明显高于APN组,差异均有统计学意义(P<0.05);AMI组心肌中Nrf2、HO-1和Bcl-2表达水平明显低于APN组,差异均有统计学意义(P<0.05);APN组LDH、CK-MB、CK、心肌细胞凋亡率、心肌中Bax和Cleaved-caspase表达水平明显低于APN+ZPP-Ⅸ组,差异均有统计学意义(P<0.05);APN组心肌中Bcl-2、HO-1表达水平明显高于APN+ZPP-Ⅸ组,差异有统计学意义(P<0.05)。结论APN在AMI模型大鼠中具有抑制心肌细胞凋亡、减轻心肌受损的作用,APN保护心肌作用的分子机制为Nrf2/HO-1通路。

Objective To investigate the effects of adiponectin(APN)on cardiac function and myocardial cell apoptosis in rats with acute myocardial infarction(AMI)through the E2 related factor 2(Nrf2)/heme oxidase 1(HO-1)pathway.Methods Healthy adult male SD rats were randomly divided into Sham group,AMI group,APN group,and APN+zinc protoporphyrin 9(ZPP-Ⅸ)group.The rats in Sham group did not be treatmented.AMI models were established by ligation of the anterior descending coronary artery in left coronary arteryin AMI group,APN group,and APN+ZPP-Ⅸ.The serum myocardial enzyme content,myocardial apoptotic genes,myocardial cell apoptosis rate,and Nrf2,HO-1 expression levels were compared between four groups.Results Serum lactate dehydrogenase(LDH),creatine kinase-MB(CK-MB),creatine kinase(CK)levels,myocardial cell apoptosis rate,the expression levels of Bax,Nrf2,HO-1,and Cleaved-caspase-3 in sham group were significantly lower than those in AMI group(P<0.05).The expression levels of Bcl-2 in sham group was significantly higher than that in AMI group(P<0.05).The levels of LDH,CK-MB,CK,myocardial cell apoptosis rate,Bax,and Cleared-caspase in AMI group were significantly higher than those in APN group(P<0.05).The expression levels of Nrf2,HO-1,and Bcl-2 in AMI group were significantly lower than those of APN group(P<0.05).The levels of LDH,CK-MB,CK,myocardial cell apoptosis rate,Bax,and Cleared-caspase in APN group were significantly lower than those of APN+ZPP-Ⅸgroup(P<0.05).The expression levels of Bcl-2 in APN group were significantly higher than that in APN+ZPP-Ⅸgroup(P<0.05).Conclusion APN has the effect of inhibiting cardiomyocyte apoptosis and reducing myocardial damage in AMI model rats.The molecular mechanism of APN protecting myocardium is Nrf2/HO-1 pathway.