摘要
目的探究异甘草酸镁(MgIG)对顺铂(CDDP)诱导大鼠心肌损伤的保护作用及机制。方法将24只Wistar大鼠随机分为正常对照组(Control组)、顺铂模型组(CDDP组)、顺铂+异甘草酸镁低剂量组(MgIG-L组)、顺铂+异甘草酸镁高剂量组(MgIG-H组),每组6只。每日监测大鼠体质量变化。给药结束后经超声心动图检测心功能指标[左室射血分数(LVEF)、左室短轴缩窄率(LVFS)、左室收缩末期内径(LVESD)、左室舒张末期内径(LVEDD)];HE染色观察心肌组织形态;酶联免疫吸附试验(ELISA)检测血清中肌酸激酶同工酶MB(CK-MB)、肌钙蛋白I(cTnI)水平;检测心肌组织匀浆中超氧化物歧化酶(SOD)、丙二醛(MDA)、谷胱甘肽(GSH)、活性氧(ROS)及亚铁离子(Fe2+)水平;Western blot法检测心肌组织中核因子E2相关因子2(Nrf2)、长链脂酰辅酶A合成酶4(ACSL4)、谷胱甘肽过氧化物酶4(GPX4)、铁蛋白重链1(FTH1)蛋白表达。结果Control组大鼠在饲养期间体质量呈增长趋势,CDDP组体质量呈降低趋势;与CDDP组相比,MgGL-L组和MgGL-H组大鼠给药5 d、9 d、13 d时体质量均增加(P<0.05)。与Control组相比,CDDP组的LVEF、LVFS降低,LVESD、LVEDD升高,心肌纤维排列紊乱、心肌纤维变形和断裂,血清CK-MB、cTnI水平升高,心肌组织中MDA、Fe2+、ROS水平升高,SOD、GSH水平降低,心肌组织中Nrf2、GPX4和FTH1蛋白表达水平降低,ACSL4蛋白表达水平升高(P<0.05)。与CDDP组相比,MgIG-L组和MgIG-H组上述指标及心肌组织病理改变均明显改善。结论异甘草酸镁通过调节心肌氧化应激水平、抑制心肌细胞铁死亡,从而改善顺铂引起的大鼠心肌损伤。
Objective To investigate the protective effect and mechanism of magnesium isoglycyrrhizinate(MgIG)on cisplatin(CDDP)-induced myocardial injury in rats.Methods Twenty-four Wistar rats were randomly divided into the normal control group,the cisplatin model group(CDDP group),the cisplatin+magnesium isoglycyrrhizinate low-dose group(MgIG-L group)and the cisplatin+magnesium isoglycyrrhizinate high-dose group(MgIG-H group),with 6 rats in each group.Changes of body mass of rats were monitored daily.At the end of drug administration,cardiac function indexes including left ventricular ejection fraction(LVEF),left ventricular short-axis narrowing rate(LVFS),left ventricular end-systolic internal diameter(LVESD)and left ventricular end-diastolic internal diameter(LVEDD)were detected by echocardiography.The morphology of myocardial tissue was observed by HE staining.Enzyme-linked immunosorbent assay(ELISA)was used to detect serum levels of creatine kinase isoenzyme MB(CK-MB)and troponin I(cTnI).Levels of superoxide dismutase(SOD),malondialdehyde(MDA),glutathione synthase(GSH),reactive oxygen species(ROS)and ferrous ion(Fe2+)in homogenates of myocardial tissue were measured biochemically.The protein expressions of nuclear factor E2-associated factor 2(Nrf2),long-chain fatty acyl coenzyme A synthase 4(ACSL4),glutathione peroxidase 4(GPX4)and ferritin heavy chain 1(FTH1)protein were detected by Western blot assay.Results The body mass of rats in the control group showed an increasing trend during feeding,and the body mass of rats in the CDDP group showed a decreasing trend.Compared with the CDDP group,the body mass of rats in the MgIG-L group and the MgIG-H group increased after 5 d,9 d and 13 d of treatment(P<0.05).Compared with the control group,the CDDP group showed decreased LVEF and LVFS,increased LVESD and LVEDD,disturbed myocardial fiber alignment,myocardial fiber degeneration and fracture,increased serum CK-MB and cTnI levels,increased levels of MDA,Fe2+and ROS in myocardial tissue,decreased levels of SOD and GSH,and decreased levels of Nrf2,GPX4,and decreased FTH1 protein expression levels and increased ACSL4 protein expression levels in myocardial tissue(P<0.05).Compared with the CDDP group,the above indicators and myocardial histopathological changes were significantly improved in the MgIG-L group and the MgIG-H group.Conclusion Magnesium isoglycyrrhizinate can ameliorate cisplatin-induced myocardial injury by regulating myocardial oxidative stress and inhibiting cardiomyocyte iron death in rats.
作者
王欣爽
安亚娟
管秀菊
李娇
刘玥
魏丽萍
齐新
WANG Xinshuang;AN Yajuan;GUAN Xiuju;LI Jiao;LIU Yue;WEI Liping;QI Xin(Graduate School,Tianjin University of Traditional Chinese Medicine,Tianjin 301617,China;Department of Cardiology,Tianjin Union Medical Center)
出处
《天津医药》
CAS
2024年第8期809-814,共6页
Tianjin Medical Journal
基金
天津市中医药管理局项目(2021028,2021155)
天津市卫生健康科技项目(TJWJ2022QN037)。
关键词
甘草酸
顺铂
心肌
氧化性应激
铁死亡
glycyrrhizic acid
cisplatin
myocardium
oxidative stress
ferroptosis
