二肽基肽酶-Ⅳ介导内皮间质转化在糖尿病肾纤维化过程中的作用及机制研究  

Effect and mechanisms of dipeptidyl peptidase-Ⅳ on endothelial-to-mesenchymal transition in diabetic kidney fibrosis

作　　者：宋丽 孙玉红[2] 施森 

机构地区：[1]四川医科大学附属第一医院麻醉科,四川泸州646000 [2]四川医科大学药理学教研室,四川泸州646000 [3]四川医科大学附属医院血管外科,四川泸州646000

出　　处：《泸州医学院学报》2016年第1期21-25,共5页Journal of Luzhou Medical College

基　　金：国家自然科学基金项目(81500643)

摘　　要：目的:探讨二肽基肽酶-Ⅳ在糖尿病肾纤维化中的作用及机制。方法:动物实验中建立糖尿病CD-1小鼠慢性肾纤维化模型,予以二肽基肽酶-Ⅳ抑制剂干预4周后,检测正常组、糖尿病组及干预组中肾脏组织中二肽基肽酶-Ⅳ的表达及内皮间质转化的变化。细胞实验中培养人微血管内皮细胞,分别予以TGFβ2及二肽基肽酶-Ⅳ抑制剂或si RNA干预,观察各组中二肽基肽酶-Ⅳ、内皮间质转化及TGFβ/smad信号通路的变化。结果:与正常小鼠相比,糖尿病小鼠肾组织表现出明显纤维化改变、高表达的二肽基肽酶-Ⅳ以及明显增强的内皮间质转化;二肽基肽酶-Ⅳ抑制剂干预后肾纤维化及内皮间质转化明显缓解及抑制。细胞实验中,二肽基肽酶-Ⅳ抑制剂或si RNA能明显降低TGFβ2诱导的内皮间质转化及TGFβ/smad信号通路。结论:二肽基肽酶-Ⅳ抑制剂能通过抑制内皮细胞间质转化来改善糖尿病肾纤维化。Objective： To analyze the roles and mechanisms of dipeptidyl peptidase-Ⅳ（DPP-Ⅳ） on endothelial-to-mesenchymal transition in diabetic kidney fibrosis. Methods： Diabetic CD1 mice were used as chronic diabetic kidney fibrosis model. Mice were treated with or without DPP-Ⅳ inhibitor for 4 weeks, kidney samples from each groups were used to analyze the pathological changes, DPP-Ⅳ protein levels, and endothelialto-mesenchymal transition. In vitro, human microvascular endothelial cells were stimulated with or without TGFβ2, and after treatment with DPP-Ⅳ inhibitor or si RNA, cell migration, DPP-Ⅳ protein levels, endothelialto-mesenchymal transition, and TGFβ/smad signaling were analyzed. Results： Diabetic CD-1 mice exhibited significant kidney fibrosis and high levels of DPP-Ⅳ expression when compared with control mice. DPP-Ⅳ inhibitor-treated diabetic mice exhibited a suppression of DPP-Ⅳ protein expression and an amelioration of kidney fibrosis associated with the inhibition of Endo MT. In cultured endothelial cells, we found that DPP-Ⅳ inhibitor inhibited TGFβ2-induced Endo MT and TGFβ/Smad signaling. Conclusion： DPP-Ⅳ inhibitor can ameliorate kidney fibrosis by suppressing Endo MT and TGFβ/Smad signaling.

关 键 词：二肽基肽酶-IV 糖尿病肾纤维化 内皮间质转化 

分 类 号：R587.1[医药卫生—内分泌] R-33[医药卫生—内科学]