基于Smad3/TGF-β/EGF2通路的红景天苷对重症中暑大鼠心功能损伤保护机制探讨  

Mechanism of salidroside protection against cardiac dysfunction in severe heat stroke rats based on Smad3/TGF-β/EGF2 pathway

作　　者：李庆敏 瞿武林[2] 陈伯钧 LI Qing-min;QU Wu-lin;CHEN Bo-jun(l.Guangzhou University of Traditional Chinese Medicine,Guangzhou 510006,China;Chenzhou First People's Hospital,Chenzhou,Hunan 423000,China)

机构地区：[1]广州中医药大学,广东广州510006 [2]郴州市第一人民医院,湖南郴州423000

出　　处：《时珍国医国药》2020年第7期1576-1580,共5页Lishizhen Medicine and Materia Medica Research

基　　金：国家自然科学基金面上项目(81700269);广东省中医药科学院治未病研究专项课题(YN2014WB09);广东省中医药科学院应用基础研究横向课题(2015KT1136)。

摘　　要：目的探讨红景天苷对重症中暑大鼠心功能损害的保护作用及机制。方法采用高温热运动及电击方式建立重症中暑大鼠模型。大鼠随机分为空白组,模型组,醒脑静组(50mg·kg-1),红景天苷低、中、高剂量组(25mg·kg-1、50mg·kg-1、100mg·kg-1)。空白组和模型组等剂量蒸馏水灌胃。酶联免疫吸附法测定丙二醛(MDA)及超氧物歧化酶(SOD)表达;聚合酶链式反应法测定辅助激活因子-1α(PGC-1α)及锰超氧化物歧化酶mRNA(MnSOD mRNA)表达;原位末端凋亡法(TUNEL)检测心肌细胞凋亡情况;流式细胞法检测心肌细胞内线粒体膜电位和氧自由基的测定;马松染色法(Masson)检测心肌组织细胞病理形态变化;蛋白质免疫印迹技术(Western-blot)检测Smad3、EGF2以及TGF-β的蛋白水平表达变化。结果与模型组比较,醒脑静组和红景天苷高剂量组大鼠线粒体膜电位、呼吸控制率及氧自由基差异具有统计学意义(P<0.01);与模型组比较,醒脑静组和红景天苷高剂量组大鼠MDA及SOD、PGC-1α及MnSOD mRNA差异具有统计学意义(P<0.01),红景天苷高剂量组和醒脑静组与模型组比较,细胞凋亡数目明显减少,且红景天苷高剂量组TUNEL显示优于醒脑静组;醒脑静组和红景天苷高剂量组大鼠心肌细胞局部裂隙缺损有明显好转;醒脑静组和红景天苷高剂量组大鼠Smad3、EGF2和TGF-β蛋白表达水平升高(P<0.01,P<0.05)。结论红景天苷可有效改善重症中暑大鼠心肌细胞病理状态,达到保护心脏功能的效果,机制可能为调控Smad3/TGF-β与EGF2信号通路上调PGC-1α、MnSOD mRNA表达有关。Objective To investigate the protective effect and mechanism of salidroside on cardiac dysfunction in severe heatstroke rats. Methods The model of severe heatstroke rats was established by high temperature thermal exercise + electric shock. The rats were randomly divided into blank group, model group, Xingnaojing group(50 mg·kg-1), low, medium and high dose group of salidroside(25 mg·kg-1, 50 mg·kg-1, 100 mg·kg-1), the blank group and the model group were orally administered with distilled water. Determination of malondialdehyde(MDA) and superoxide dismutase(SOD) by enzyme-linked immunosorbent assay;detection of coactivator-activated factor-1α(PGC-1α) and manganese superoxide dismutase mRNA(MnSOD) by polymerase chain reaction expression of mRNA);apoptosis of cardiomyocytes detected by TUNEL;flow cytometry for detection of mitochondrial membrane potential and oxygen free radicals in cardiomyocytes;Mason staining(Masson) for detection of myocardial cell pathology morphological changes;Western-blot detection of changes in protein expression levels of Smad3, EGF2 and TGF-β. Results Compared with the model group, the mitochondrial membrane potential, respiratory control rate and oxygen free radicals in the high-dose group of Xingnaojing group and salidroside were statistically significant(P<0.01). Compared with the model group, the brain was refreshed. The MDA, SOD, PGC-1α and MnSOD mRNA in the high dose group of Jingjing and salidroside were statistically significant(P<0.01). The high dose of salidroside and the Xingnaojing group were compared with the model group. The number of apoptosis was significantly reduced, and the high dose of salidroside TUNEL was better than that of Xingnaojing group;the local fissure defect of myocardial cells in the high dose group of Xingnaojing and salidroside was significantly improved;The expression levels of Smad3, EGF2 and TGF-β protein in the high dose group and the salidroside group were increased(P<0.01, P<0.05).Conclusion Salidroside can effectively improve the patholo

关 键 词：红景天苷 重症中暑 大鼠 心功能损害 保护作用 机制 

分 类 号：R285.5[医药卫生—中药学]