摘要
目的观察肾康丸及依那西普对2型糖尿病(T2DM)大鼠肾组织肿瘤坏死因子相关凋亡诱导配体(TRAIL)系统表达的影响,探讨两种药物对肾脏保护的作用机制。方法建立T2DM大鼠模型为模型组(D组),成模后将大鼠随机分为3组:模型对照组(DM组)、肾康丸组(DS组)、依那西普组(DE组);另设正常对照组(C组)。分组干预,全自动生化仪检测尿素氮(BUN)、血肌酐(Scr)及空腹血糖(FBG);ELISA法检测尿微量白蛋白(Uα1-MG)、24 h尿微量白蛋白(24hUm-Alb);Q-RT-PCR法检测治疗后TNF-α、TRAIL、DR4、DcR2在各大鼠肾组织的表达,HE染色法观察大鼠肾组织病理变化。结果 DM组BUN、Scr及FBG上升,与DM组相比,DS组与DE组BUN、Scr、及FBG下降。与C组相比,第4周、第8周DM组大鼠Uα1-MG、24hUm-Alb比其他3组显著升高(P<0.01),肾组织TNF-α、DcR2 mRNA表达显著增强(P<0.01);而TRAIL、DR4 mRNA表达显著减弱(P<0.01),并且DM组大鼠出现了肾脏组织病理损害;DS组及DE组的肾脏病理损害较DM组轻。结论肾康丸与特异性TNF-α拮抗剂依那西普均对T2DM大鼠肾脏有显著保护作用,但两者作用机制不全一致,依那西普主要减少TNF-α表达,减轻炎症反应作用,而肾康丸是通过影响TRAIL系统的表达。
Objective To investigate the effects of Shenkangan and etanercept on the expression of tumor necrosis factor-related apoptosis-inducing ligand system(TRAIL)in kidney of type 2 diabetic rats.Methods The rat models of type 2 diabetes were randomly divided into diabetic model group(DM),Shenkangwan treatment group(DS)and etanercept treatment group(DE);while the rat fed with normal chow were selected as the control group(C).After treatment,the BUN,SCr and FBG were assessed by automatic biochemical analyzer.The levels of urineα1-MG(Uα1-MG)and 24 hour urine mAlb(24 UmAlb)were measured by ELISA;and the expression of TRAIL,death receptor 4(DR4)and decoy receptor 2(DcR2)proteins and mRNA in the kidney were measured by immune histochemietry and quantitative real-time PCR(Q-RT-PCR).The renal pathological change was observed under optical microscope with Hematoxylin and Eosin(HE)staining.Results The levels of BUN,SCr and FBG were increased in the Group DM,which were all reversed after treatment with Shenkangwan and etanercept.Compared with Group C,the levels of Uα1-MG,and 24 hUm-Alb,and the renal expression of TNF-αand DcR2 proteins and mRNA were significantly increased(P<0.01).However,the expression of TRAIL and DR4 proteins and mRNA were significantly reduced,with renal pathological lesion in the Group DM(P<0.01).These changes were all reversed and the renal pathological lesion was mitigated after treatment with Shenkangwan and etanercept.Conclusion Shenkangwan and etanercept have significant renal protection on T2 DM rats.But their mechanisms may be different.The mechanism of etanercept may be the effects on expression of TNF-αand Shwnkangwan′s is the effects on expression of TRAIL system.
作者
方婉
刘雅诗
刘龙辉
张子鑫
刘小玲
李燕霞
杨爱成
FANG Wan;LIU Ya-shi;LIU Long-hui;ZHANG Zi-xin;LIU Xiao-ling;LI Yan-xia;YANG Ai-cheng(Graduate School,Hunan University of TCM,Changsha 410000,Hunan,China)
出处
《广东医学》
CAS
2019年第16期2283-2288,共6页
Guangdong Medical Journal
基金
江门市科学技术局计划项目(编号:2014020)
