黄连素抑制心肌细胞凋亡改善大鼠心肌缺血再灌注损伤的机制研究

Effect of berberine on myocardial apoptosis and myocardial ischemia-reperfusion injury in rats

目的探讨黄连素预防大鼠急性心肌缺血再灌注损伤中的机制。方法大鼠随机分为空白对照组、假手术组、模型组和黄连素给药组,每组15只。黄连素给组灌胃100 mg/kg的黄连素药物,其余3组灌胃相应体积的药物溶剂,每天定时灌胃1次。给药两周后模型组和黄连素给药组进行大鼠急性心肌缺血再灌注造模,假手术组不造成动物心肌急性缺血,对照组大鼠只麻醉,其余操作相同。检测各组超氧化物歧化酶(SOD)、乳酸脱氢酶(LDH)及丙二醛(MDA)水平,以及凋亡相关蛋白含半胱氨酸的天冬氨酸蛋白水解酶-3(Caspase-3)、B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关x蛋白(Bax)水平。结果黄连素给药组[(43.29±5.58)%]大鼠心肌梗死面积低于模型组[(25.39±4.26)%],差异有统计学意义(P<0.05)。与对照组比较,模型组SOD水平降低,LDH、MDA水平上升,Bax、Caspase-3的蛋白和基因表达水平上升,Bax/Bcl-2基因表达水平上升,Bcl-2的蛋白和基因表达水平降低,差异均有统计学意义(P<0.05);与模型组比较,黄连素给药组SOD水平上升,LDH、MDA水平降低,Bax、Caspase-3的蛋白和基因表达水平降低、Bax/Bcl-2基因表达水平降低,Bcl-2的蛋白和基因表达水平上升,差异均有统计学意义(P<0.05)。结论黄连素可通过降低心肌过氧化进而抑制心肌细胞凋亡改善大鼠急性心肌缺血再灌注损伤。

Objective To investigate the mechanism of berberine in preventing acute myocardial ischemia-reperfusion injury in rats.Methods Rats were randomly divided into blank control group,sham operation group,model group and berberine group with 15 rats in each group.The berberine group was given 100 mg/kg berberine by gavage,and the other three groups were given corresponding volume of drug solvent,once a day.Two weeks after administration,the model group and berberine group were subjected to myocardial ischemia-reperfusion.The sham operation group did not cause acute ischemia,while the control group was anesthetized,and the other operations were the same.The levels of superoxide dismutase(SOD),lactate dehydrogenase(LDH),malondialdehyde(MDA)and the relative expression levels of apoptosis related proteins cysteine-containing aspartate proteolytic enzyme-3(Caspase-3),B lymphoma-2(Bcl-2),Bcl-2 related x protein(Bax)were detected.Results The infarct size of berberine group[(43.29±5.58)%]was lower than that of model group[(25.39±4.26)%],and the differences were statistically significant(P<0.05).Compared with the control group,the levels of SOD was decreased,the levels of LDH and MDA were increased,the protein and gene expression levels of Bax and Caspase-3 were increased,the expression level of Bax/Bcl-2 gene was increased,and the protein and gene expression levels of Bcl-2 were decreased in the model group(P<0.05);compared with the model group,the level of SOD was increased,the levels of LDH and MDA were decreased,the protein and gene expression levels of Bax,Caspase-3 were decreased,the gene expression level of Bax/Bcl-2 was decreased,and the protein and gene expression levels of Bcl-2 were increased(P<0.05)in berberine group.Conclusion Berberine can improve the acute myocardial ischemia-reperfusion injury in rats by reducing myocardial peroxidation and then inhibiting cardiomyocyte apoptosis.