吡格列酮对急性肾损伤模型大鼠的影响及相关机制研究  

Effects of pioglitazone on rat model of acute kidney injury and related mechanism

作　　者：俞燕[1] 范亚平[1] 胡翠容 袁莉[1] 陈荣荣[1] 戴厚永[1] YU Yan;FAN Yaping;HU Cuirong;YUAN Li;CHEN Rongrong;DAI Houyong(Department of Nephrology,the Affiliated Hospital of Nantong University,Nantong,Jiangsu 226001,China;Department of Nephrology,NingBo Hangzhou Bay Hospital,Ningbo,Zhejiang 315000,China)

机构地区：[1]南通大学附属医院肾内科,江苏226001 [2]浙江省宁波市杭州湾医院肾内科,315000

出　　处：《重庆医学》2018年第A01期4-7,共4页Chongqing medicine

基　　金：南通市科技计划项目(MS22015115)。

摘　　要：目的观察吡格列酮对顺铂诱导的急性肾损伤(AKI)模型大鼠的影响并探讨其相关机制。方法将30只清洁雄性SD大鼠采用随机数字表法分为对照组(A组)、吡格列酮组(B组)、AKI模型组(C组)和AKI模型给予不同剂量吡格列酮干预组(D组、E组、F组);每组5只。C、D、E、F组给予腹腔单次注射顺铂注射液(10 mg/kg)。B、D、E、F组分别给予不同剂量吡格列酮连续灌胃3 d(10、5、10、15 mg·kg-1·d-1)。造模成功后72 h测定各组大鼠血肌酐、尿素、脂联素、肿瘤坏死因子-ɑ(TNF-ɑ)等,观察大鼠组织病理学改变,并进行相关分析。结果与A组大鼠比较,C组大鼠血肌酐、尿素、脂联素、TNF-α水平均明显升高,差异均有统计学意义(P<0.05),肾间质及肾小管损伤明显;给予不同剂量吡格列酮干预后大鼠血肌酐、尿素、TNF-α水平均明显降低,血清脂联素水平均明显升高,差异均有统计学意义(P<0.05),病理损伤减轻;A、C、D、E、F组大鼠血清脂联素水平与TNF-α水平呈明显负相关(r=-0.14、-0.69、-0.79、-0.90、-0.92,P<0.05)。结论吡格列酮可改善AKI模型大鼠肾功能及肾小管间质损伤,其机制可能包括提高血清脂联素水平、抑制炎性细胞因子——TNF-α的释放,从而延缓肾小管间质损伤的发生与进展。Objective To investigate the effects of pioglitazone on rat model of acute kidney injury and related mechanism.Methods SD rats were randomly divided into different groups:control group(A group),piogilitazone group(10 mg·kg-1·d-1 by gavage,B group),acute kidney injury model group(cisplatin 10 mg/kg ip,C group)and different doses of pioglitazone intervention groups(cisplatin 10 mg/kg ip,then pioglitazone 5,10,15 mg·kg-1·d-1 by gavage,D,E and F groups resp).72 hours after the succesful modeling,all the rats were sacrificed,and blood samples were collected for analysis of renal function,tumor necrosis factor-α(TNF-α),and adiponectin concentration.Renal Tissue specimens were collected for HE staining.Results Compared with A group,the levels of serum creatinine,urea,adiponectin and TNF-αwere significantly increased in C group with obvious damages of renal interstitium and tubules(P<0.05).Compared with C group,the levels of serum creatinine,urea,and TNF-αwere significantly decreased,and the concentration of adiponectin was increased in D,E,and F groups with mitigate damages of renal interstitium and tubules(P<0.05).The correlation analysis showed that adiponectin was negatively correlated with TNF-αlevel(P<0.05).Conclusion Serum adiponectin increased by pioglitazone ameliorate renal function and attenuate renal damage in acute kidney injury rat model.This renal protective effect is possibly related with reduced TNF-α.

关 键 词：急性肾损伤 吡格列酮 脂联素 肿瘤坏死因子-Α 

分 类 号：R338.26[医药卫生—人体生理学]