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
周星宇 1何艺林 2付丹 3孙赛格 1刘秋嫣 3徐力 2钱凯3
作者信息
- 1. 宜春学院化学与生物工程学院,江西宜春 336000;宜春学院医学院,江西宜春 336000
- 2. 江西承葛生物科技有限公司,江西宜春 336000
- 3. 宜春学院医学院,江西宜春 336000
- 折叠
摘要
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(collagen Ⅰ)、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.
Abstract
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,Collagen Ⅰ and 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.
关键词
异甘草酸镁/心肌重构/细胞凋亡/氧化应激/异丙肾上腺素/PI3K/AKT1Key words
magnesium isoglycyrrhizinate/myocardial remodeling/apoptosis/oxidative stress/isoproterenol/PI3K/AKT1引用本文复制引用
基金项目
江西省自然科学基金(20202BABLI216078)
出版年
2024
NETL
NSTL
万方数据