[1]刁俊玲,刘灵俪,杜 鹃,等.新型PPARγ激动剂CMHX008对高脂饮食诱发的糖尿病肾病的改善作用[J].中国药理学通报,2018,(08):1114-1119.[doi:10.3969/j.issn.1001-1978.2018.08.017]
 DIAO Jun-ling,LIU Ling-li,DU Juan,et al.CMHX008, a novel PPARγ partial agonist,improves renal function in HFD-induced obese mice with diabetic nephropathy[J].Chinese Pharmacological Bulletin,2018,(08):1114-1119.[doi:10.3969/j.issn.1001-1978.2018.08.017]
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新型PPARγ激动剂CMHX008对高脂饮食诱发的糖尿病肾病的改善作用()
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《中国药理学通报》[ISSN:/CN:]

卷:
期数:
2018年08期
页码:
1114-1119
栏目:
论著
出版日期:
2018-07-26

文章信息/Info

Title:
CMHX008, a novel PPARγ partial agonist,improves renal function in HFD-induced obese mice with diabetic nephropathy
文章编号:
1001-1978(2018)08-1114-06
作者:
刁俊玲1刘灵俪2杜 鹃1李佳渝1李继斌2肖晓秋1
重庆医科大学 1.附属第一医院重大代谢性疾病转化医学重庆市高校重点实验室、2.公共卫生与管理学院, 重庆 400016
Author(s):
DIAO Jun-ling1 LIU Ling-li2 DU Juan1 LI Jia-yu1 LI Ji-bin2 XIAO Xiao-qiu1
1.Chongqing Key Laboratory of Translational Medicine in Major Metabolic Disease, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016,China; 2.School of Public Health and Management, Chongqing Medical University, Chongqing 400016,China
关键词:
罗格列酮 PPARγ 糖尿病肾病 肾功能损伤 肾小管间质纤维化 胶原纤维
Keywords:
rosiglitazone PPARγ diabetic nephropathy renal function injury tubulointerstitial fibrosis collagen
分类号:
R-332; R322.61; R392.11; R587.1; R692.390.22; R977.15
DOI:
10.3969/j.issn.1001-1978.2018.08.017
文献标志码:
A
摘要:
目的 探寻新型PPARγ激动剂CMHX008对高脂饮食诱发的糖尿病小鼠肾脏功能的影响。方法 采用高脂饮食诱发的2型糖尿病小鼠为模型,随机分为:高脂空白组(HV组)、罗格列酮组(HR组)、CMHX008组(HC组),低脂饮食喂养的小鼠给予等量溶媒作为低脂空白组(LV组)。收集小鼠尿液和血清,行全自动生化分析检测; 苏木精-伊红(HE)染色观察肾脏组织形态; 天狼星红和Masson染色显示肾脏胶原纤维的沉积; 实时荧光定量PCR检测肾小管上皮细胞表型转化相关标志物mRNA的相对表达量。结果 HR组和HC组的尿蛋白/肌酐、HC组血尿素氮和血肌酐浓度较HV组减少; HE染色发现,HR和HC组肾小管损伤较HV组明显改善; 天狼星红及Masson染色显示,HR组和HC组肾脏纤维化较HV组明显减少; qPCR结果显示,HR组和HC组α-平滑肌肌动蛋白、I型胶原、纤连蛋白mRNA表达较HV组明显下调,E-钙黏蛋白mRNA表达明显上调。结论 长期高脂饮食诱发的糖尿病小鼠肾脏受损,同时给予CMHX008能明显减弱肾脏的纤维化,改善肾功能的损伤。
Abstract:
Aim To investigate the effect of CMHX008, a novel PPARγ partial agonist, on renal function of diabetic nephropathy in high-fat diet(HFD)fed mice in comparison with traditional insulin sensitizer rosiglitazone.Methods Male C57BL/6 mice fed with HFD were randomly divided into vehicle group(HV), rosiglitazone group(HR)and CMHX008 group(HC), with vehicle treated low fat diet mice(LV)as a control.The urine and serum samples were collected to detect related indicators by automatic biochemical analyzer; Hematoxylin-eosin(HE)staining was used to reveal the histomorphology of kidney; the renal collagen accumulation was assayed by Sirius red and Masson's trichrome staining; the mRNA levels of α-smooth muscle actin(α-SMA), E-cadherin(E-cad), collagen I and fibronectin in kidney were assessed by quantitative real time RT-PCR.Results HR group and HC group showed a decrease of urinary protein/ creatinine ratio(Upro/Cr), serum creatinine levels(Scr)and blood urea nitrogen(BUN)in serum treated with CMHX008 were significantly decreased; HE staining revealed rosiglitazone and CMHX008 could obviously improve HFD induced tubular injury; Sirius red and Masson's trichrome staining revealed less accumulation of collagen in HR and HC group than in HV group.Compared with HV group, kidney mRNA levels of HR group and HC group showed down-regulated expression of α-SMA, collagen I, and fibronectin, and up-regulated expression of E-cadherin.Conclusion Treatment of rosiglitazone and CMHX008 can effectively attenuate renal fibrosis and improve renal function in HFD-induced diabetic nephropathy mice.

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备注/Memo

备注/Memo:
收稿日期:2018-03-15,修回日期:2018-04-22
基金项目:国家自然科学基金面上项目(No 81570763); 重庆市基础与前沿研究计划项目(No cstc2015jcyjBX0132)
作者简介:刁俊玲(1993-),女,硕士生,研究方向:代谢性疾病的发病机制和干预对策,E-mail:928935038@qq.com;
肖晓秋(1964-),男,博士,教授,博士生导师,研究方向:代谢性疾病的发病机制和干预对策,通讯作者,E-mail: bshaw2001@163.com
更新日期/Last Update: 2018-07-26