摘要
目的 探索外源性睾酮(TP)致大鼠肾脏损伤的作用及可能机制.方法 SD雄性大鼠48只,随机分为6组(每组8只):control组、TP组、TP+氯喹(CQ)组、TP+甘草甜素(Gly)组、CQ(自噬抑制剂)组、Gly〔高迁移率族蛋白(HMG)B1抑制剂〕组.各组大鼠处理21 d后,测量其体重、肾脏湿重、计算肾脏指数;苏木素-伊红(HE)染色观察大鼠肾脏组织病理形态学变化;免疫组化法和Western印迹印迹法分析大鼠肾脏组织自噬相关蛋白LC3B-Ⅱ、Beclin1、P62、HMGB1的定位和表达情况.结果 与control组比较,TP组大鼠肾脏湿重、肾脏指数无明显变化(P>0.05);肾小球毛细血管襻多呈分叶状改变,肾小囊间隙变窄,肾小管上皮细胞水肿,管腔变窄;肾脏组织LC3B-Ⅱ、Beclin1和HMGB1蛋白表达水平上调(P<0.05),联合给予TP与CQ后,仅见少数肾小体血管球呈分叶状改变,肾小管水肿明显减轻;Beclin1、LC3B-Ⅱ和HMGB1蛋白表达水平均下调(P<0.05);TP+Gly组大鼠肾脏组织病理学改变及自噬相关蛋白表达水平结果 与TP+CQ组类似.结论 外源性TP可能通过上调细胞自噬致大鼠肾脏组织损伤的发生,HMGB1可能参与此过程自噬水平的调节.
Objective To explore the role and possible mechanism of exogenous testosterone inducing renal injury in rats.Methods Forty-eight SD male rats were randomly divided into 6 groups(8 in each group):control,testosterone(TP),androgen+chloroquine(TP+CQ),androgen+glycyrrhizin(TP+Gly),chloroquine(autophagy inhibitor,CQ),glycyrrhizin(Gly,HMGB1 inhibitor)groups.After treatment for 21 days,the body weight,kidney wet weight and kidney index were measured.HE staining was used to observe the pathological changes of rat kidney.Immunohistochemistry and Western-blot were used to analyze the location and expression of autophagy proteins of rat kidney LC3B-Ⅱ,Beclin1,P62,HMGB1.Results Compared with the control group,there was no significant change in kidney wet weight and kidney index in the TP group(P>0.05).In TP group,the glomerular capillary vasospasm was lobulated,the renal capsule gap was narrowed,renal tubular epithelial cells were edematous,the lumen was narrowed;the expression levels of LC3B-Ⅱ,Beclin1 and HMGB1 in kidney tissues were up-regulated(P<0.05).After combined administration of TP and CQ,only a small number of renal glomeruli were lobulated,and tubular edema was significantly reduced;Beclin1,LC3B-Ⅱand HMGB1 protein expression levels were down-regulated(P<0.05).In TP+Gly group,the pathological changes of rat kidney and the expression levels of autophagy-related proteins were similar to those of the TP+CQ group.Conclusions Exogenous testosterone might up-regulate the injury of rat kidney tissue by up-regulating autophagy.HMGB1 might be involved in the regulation of autophagy.
作者
李旭
聂黎虹
秦凯悦
朱亚洲
张航
李佳鑫
赵瑞宁
LI Xu;NIE Li-Hong;QIN Kai-Yue(Graduate School,Ningxia Medical University,Yinchuan 750004,Ningxia,China)
出处
《中国老年学杂志》
CAS
北大核心
2020年第7期1503-1507,共5页
Chinese Journal of Gerontology
基金
国家自然科学基金(81460148)
大学生创新创业计划项目(NXCX2018106)。
关键词
肾脏损伤
睾酮
自噬
Kidney damage
Androgens
Autophagy
作者简介
第一作者:李旭(1991-),男,在读硕士,主要从事泌尿系统疾病研究;通信作者:赵瑞宁(1973-),男,主任医师,博士,副教授,硕士生导师,主要从事泌尿系统疾病研究;李佳鑫,宁夏医科大学2017级本科生.
