异甘草酸镁调控氧化应激和凋亡改善小鼠心肌重构的机制

Magnesium isoglycyrrhizinate improved myocardial remodeling through regulating oxidative stress and apoptosis

目的:探讨异甘草酸镁(magnesium isoglycyrrhizinate,MgIG)治疗异丙肾上腺素(isoproterenol,ISO)诱导的的小鼠心肌重构的机制。方法:选用SPF级雄性小鼠随机分组法分为4组,即对照(control)组、阳性(control+MgIG)组、模型(ISO)组、治疗(ISO+MgIG)组。试剂盒检测血清中谷胱甘肽过氧化物酶(glutathione peroxidase,GSH-Px)、肌酸激酶同工酶(creatine kinase isoenzyme,CK-MB)、丙二醛(malondialdehyde,MDA)和乳酸脱氢酶(lactate dehydrogenase,LDH)的含量。苏木精-伊红/马松(HE/Masson)染色检测心脏组织的病理变化。Western blot检测心脏组织中相关蛋白的表达。结果:通过血清检测、HE/Masson染色和蛋白表达发现,ISO可造成小鼠心肌损伤:心脏体积、心脏质量、MDA、LDH、Ⅰ型胶原纤维(collagenⅠ)、磷酸化磷脂酰肌醇-3-激酶(phosphorylated phosphatidylinositol-3-kinase,p-PI3K)、半胱氨酸蛋白酶-3激活型(cleaved caspase-3)和磷酸化蛋白激酶B(p-AKT1)等表达量均高于control组(P<0.05),GSH-Px、B淋巴细胞瘤-2(Bcl-2)、环氧合酶-2(COX-2)和超氧化物歧化酶(SOD1)等表达量均低于control组(P<0.05)。MgIG能逆转ISO对心脏的损伤,使小鼠各项指标得以改善(P<0.05)。结论:对于ISO诱导的的心肌重构,异甘草酸镁具有改善作用,其作用机制可能与抑制PI3K/AKT1通路调控细胞凋亡和氧化应激有关。

OBJECTIVE To explore the therapeutic mechanism of magnesium isoglycyrrhizinate(MgIG)for myocardial remodeling induced by isoproterenol(ISO)in mice.METHODS A total of 60 male mice of specific pathogen free(SPF)grade were assigned into 4 groups of blank control(control),positive control(control+MgIG),model(ISO)and treatment(ISO+MgIG).The serum contents of glutathione peroxidase(GSH-Px),creatine kinase isoenzyme(CK-MB),malondialdehyde(MDA)and lactate dehydrogenase(LDH)were detected by kits.The pathological changes of heart tissue were observed after hematoxylin-eosin(HE)/Masson stain.And the expressions of related proteins in heart tissue were detected by Western blot.RESULTS Serum detection,HE/Masson stain and protein expression indicated that ISO could cause myocardial injury in mice.As compared with control group,heart volume/mass,MDA,LDH,CollagenⅠand phosphorylated phosphatidylinositol-3-kinase(p-PI3K)spiked in ISO group.The expressions of cleaved caspase-3 and phosphorylated protein kinase B(p-AKT1)were up-regulated(P<0.05)while those of GSH-Px,Bcl-2,COX-2 and SOD1 down-regulated(P<0.05).However,MgIG could reverse the cardiac damage of ISO and improve all parameters(P<0.05).CONCLUSION MgIG can improve myocardial remodeling induced by ISO and its mechanism may be correlated with an inhibition of PI3K/AKT1 pathway for regulating apopto⁃sis and oxidative stress.It shall provide new rationales for clinical applications of MgIG on myocardial injury.