人参皂苷Rg1通过调控缝隙连接拮抗铅致大鼠心肌细胞损伤的作用机制  

Mechanism of ginsenoside Rg1 antagonising lead-induced cardiomyocyte injury in rats by modulating gap junctions

作　　者：李艺 王琼 冯斌[1] 何珍[1] LI Yi;WANG Qiong;FENG Bin;HE Zhen(Shandong Provincial Academy of Occupational Health and Occupational Medicine,Jinan,Shandong 250062,China;Shandong First Medical University/Shandong Provincial Academy of Medical Sciences;不详)

机构地区：[1]山东省职业卫生与职业病防治研究院,山东济南250062 [2]山东第一医科大学/山东省医学科学院 [3]济南市疾病预防控制中心

出　　处：《中国工业医学杂志》2024年第2期118-122,132,I0001,共7页Chinese Journal of Industrial Medicine

基　　金：山东省中医药科技项目(编号:2021Z038)。

摘　　要：目的 观察醋酸铅染毒大鼠经人参皂苷Rg1(ginsenoside Rg1,以下简称Rg1)干预前后心肌缝隙连接蛋白Cx43(connexin 43,Cx43)及其磷酸化蛋白(p-Cx43)的表达变化,探究Rg1通过缝隙连接对铅致心肌细胞损伤的保护作用。方法 将无特定病原体级的Sprague Dawley雄性大鼠按随机数字表法分为对照组,以二甲基亚砜(DMSO)溶解辛醇,作为辛醇对照组,辛醇为Cx43特异性阻滞剂,设置DMSO组及辛醇组,且不做干预;低、中、高剂量铅染毒组(90、180、360 mg/kg),Rg1干预组分为不同剂量铅染毒+Rg1组、辛醇+Rg1组、高剂量铅染毒+辛醇+Rg1组(Pb 360 mg/kg+辛醇+Rg1),共11组,每组8只。对照组给予等量蒸馏水,DMSO组、辛醇组按照体质量进行腹腔注射染毒(5 mmol/kg),不同剂量铅染毒组和铅染毒+Rg1组经口灌胃醋酸铅溶液,每天染毒1次,每周连续5 d,造模4周后,各Rg1(20 mg/kg)干预组每天给药1次,每周连续5 d,共4周;对照组及不同剂量铅染毒组每天经口灌胃蒸馏水。4周后处死大鼠收集心脏组织,计算心脏脏器系数,观察心肌组织病理学变化,检测全血血铅浓度,Cx43、p-Cx43、Bcl-2、Bax、Cleaved caspase-3、LC3-Ⅰ和LC3-Ⅱ蛋白表达水平。结果 与对照组相比,染毒组血铅水平显著升高(P<0.05);高剂量铅染毒组心脏脏器系数显著降低,Rg1干预后脏器系数升高(P<0.05)。HE染色显示,对照组、DMSO组及辛醇组心肌结构无明显变化;低、中剂量铅染毒组出现心肌纤维排列紊乱;高剂量铅染毒组心肌纤维断裂。与铅染毒组、辛醇组相比,Rg1干预组心肌组织结构明显改善,心肌纤维排列相对整齐紧密,无明显炎症。Western blot检测结果显示,铅染毒组Cx43、p-Cx43、Bcl-2及LC3-Ⅰ蛋白表达低于对照组(P<0.05),Bax、Cleaved caspase-3及LC3-Ⅱ蛋白表达高于对照组(P<0.05);Rg1干预组Cx43、p-Cx43、Bcl-2及LC3-Ⅰ蛋白表达高于各剂量铅染毒组(P<0.05),Bax、Cleaved caspase-3及LC3-Ⅱ蛋白表达低于各剂�Objective To observe the changes in the expression of myocardial gap junction protein Cx43(Cx43)and its phosphorylated protein(p-Cx43)before and after the intervention of ginsenoside Rg1(Rg1)in lead acetate-contaminated rats,and to investigate the protective effect of Rg1 on lead-induced cardiomyocyte injury through gap junctions.Methods Sprague Dawley male rats without specific pathogen grade were divided into control groups by random number table method,and octanol was dissolved in DMSO as a control group of octanol,which is a Cx43-specific blocker,setting DMSO group,octanol(Oct)group,low,medium and high dose of Pb trained and poisoned group(90,180 and 360 mg/kg)and Rg1 intervention group as low,medium and high dose of Pb poisoning+Rg1 intervention group,Oct+Rg1 intervention group,and high dose lead poisoning+Oct+Rg1 intervention group(Pb 360 mg/kg+Oct+Rg1),totalling 11 groups of 8 animals each.The control group was given an equal amount of distilled water,the DMSO group and the octanol group(5 mmol/kg)were stained by peritoneal injection according to their body mass,and different doses of lead-stained groups(90,180,360 mg/kg)and each dose of lead-stained+Rg1 group were stained by oral gavage of the lead acetate solution once a day for 5 d consecutive per week.After 4 weeks of modeling,Rg1(20 mg/kg)intervention was administered once daily for 5 d consecutive per week for 4 weeks in each group;distilled water was orally gavaged daily in the control group and the low,medium,high dose lead-stained groups.Cardiac tissues were collected from rats after 4 weeks of execution,cardiac apparatus coefficients were calculated,myocardial histopathological changes were observed,and whole blood lead concentration,Cx43,p-Cx43,Bcl-2,Bax,Cleaved caspase-3,LC3-Ⅰand LC3-Ⅱprotein expression levels were detected.Results Blood lead levels were significantly higher in all tainted groups compared to the control group(P<0.05);cardiac apparatus coefficient levels were significantly lower in the high-dose tainted group(360 mg/kg)and h

关 键 词：人参皂苷Rg1(Rg1) 醋酸铅 缝隙连接蛋白43(Cx43) 

分 类 号：R135.11[医药卫生—劳动卫生] R994.3[医药卫生—公共卫生与预防医学]