Effects and the possible mechanism of histone deacetylase inhibitor SAHA on the interstitial fibrosis induced by diabetes
10.3760/cma.j.issn.1001-7097.2017.12.008
- VernacularTitle:组蛋白去乙酰化酶抑制剂SAHA对糖尿病大鼠肾间质纤维化的影响及机制
- Author:
Yuanyuan WANG
1
;
Yanwen MAO
;
Xiaohuan ZHANG
;
Wei PENG
;
Lingling LIU
;
Huiming LIU
;
Mingjun SHI
;
Ying XIAO
;
Yingying ZHANG
;
Bing GUO
Author Information
1. 贵州医科大学病理生理学教研室贵州医科大学重大疾病发病机制及药物防治特色重点实验室
- Keywords:
Diabetic nephropathies;
Fibrosis;
Smad7;
Suberoylanilide hydroxamic acid
- From:
Chinese Journal of Nephrology
2017;33(12):929-934
- CountryChina
- Language:Chinese
-
Abstract:
Objective To explore the effects and possible mechanism of histone deacetylase inhibitor SAHA on the interstitial fibrosis induced by diabetes.Methods The SD rats were divided into three groups:control group (Con,n=9),diabetes mellitus (DM) group (n=9) and SAHA treatment group (n=9).The diabetic rat model was established by injecting streptozotocin (STZ) through tail vein.After 8 weeks,the SAHA treatment group rats were fed with a SAHA solution (25 mg· kg-1 · d-1) by gastric gavage.After 16 weeks,all rats were sacrificed to detect relevant biochemical parameters,and observe the changes of pathomorphology in kidney.In addition,immunohistochemistry staining and Western blotting were employed to detect the protein expressions of transforming growth factor-β1 (TGF-β1),Smad2,Smad3,p-Smad2,p-Smad3,Smad7,collagen-Ⅰ and collagen-Ⅲ,respectively.Results Compared with Con group,the levels of blood glucose (BG),urinary trace albumin/urinary creatinine (ACR),triglyceride (TG) and total cholesterol (TC) in the diabetic group were all increased significantly (all P ＜ 0.05),the protein expressions of TGF-β1,p-Smad2,p-Smad3,collagen-Ⅰ and collagen-Ⅲ in kidney were all increased in diabetic group (all P ＜ 0.05),and the expression of Smad7 was significantly reduced (P ＜ 0.05).Compared with DM group,the levels of ACR was reduced,the renal fibrosis was alleviated,the protein expressions of TGF-β1,p-Smad2,p-Smad3,collagen-Ⅰ and collagen-Ⅲ in SAHA group were all decreased (all P ＜ 0.05),and the expression of Smad7 was increased significantly (P ＜ 0.05).Conclusion SAHA may restore the protein level of Smad7 by enhancing protein stability,then promote the moderate transduction of TGF-β1/Smads signaling pathway,which reduce the fibrosis of renal tubules in diabetic rats.
