Effects of pirfenidone on renal fibrosis in mice with diabetic nephropathy and its mechanisms
10.3760/cma.j.issn.1001-7097.2018.09.008
- VernacularTitle:吡非尼酮在治疗糖尿病肾病小鼠肾纤维化中的作用及机制
- Author:
Feifei XIE
1
;
Miaomiao LU
;
Xiao FU
;
Wenjuan MEI
;
Xiaohua LIAO
;
Sha TU
;
Qunjuan LEI
;
Qianbin LI
;
Gaoyun HU
;
Lijian TAO
;
Zhangzhe PENG
Author Information
1. 中南大学湘雅医院肾内科
- Keywords:
Diabetic nephropathy;
Glomerular mesangial cells;
Fibrosis;
Inflammatory;
Pirfenidone
- From:
Chinese Journal of Nephrology
2018;34(9):689-696
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate effects of pirfenidone (PFD) on diabetic nephropathy model in db/db mice and to explore its possible mechanisms.Methods (1) Wild-type mice were as the normal control group,and db/db mice were divided into model group and PFD group,with 6 mice in each group.In the PFD group mice were administered continuously by 250 mg· kg-1· d-1 PFD for 18 weeks,and mice in the other two groups were administered by 0.5％ sodium carboxymethyl cellulose.Blood glucose and 24 h urinary albumin were measured.The pathological changes of renal tissue were evaluated by PAS staining,PASM staining,Masson staining and Sirius red staining.The expression of collagen type Ⅳ in kidney tissues was detected by immunohistochemistry.(2) Mouse mesangial cells (SV40 MES-13 cells) were cultured as research objects.They were divided into control group,hyperosmolar group,high glucose (HG) group,and 50,100,200,400,800,1600 mg/L PFD+HG group.BrdU cell proliferation test was used to evaluate cell proliferation rate.Cells were divided into control group,hyperosmolar group,HG group and PFD+HG group.The mRNA expressions of α-smooth muscle actin (α-SMA),collagen type Ⅰ,collagen type Ⅳ,transforming growth factor-β1 (TGF-β1),interleukin (IL)-1β,IL-6 and monocyte chemotactic protein-1 (MCP-1) were detected by real-time PCR.Results (1) Compared with normal control group,the model mice had higher weight,blood glucose and 24 h urinary albumin,accompanied with glomerular hypertrophy,mesangial area expansion,tubulointerstitial fibrosis and deposition of collagen type Ⅳ (all P ＜ 0.05).Compared with those in model group,in PFD group 24 h urinary albumin decreased,glomerular hypertrophy,mesangial area expansion and tubulointerstitial fibrosis alleviated,and the protein expression of collagen type Ⅳ inhibited (all P＜0.05).(2) Compared with those in HG group,MES-13 cell proliferation rates of 100,200,400,800,1600 mg/L PFD+HG groups decreased (all P ＜ 0.05),and the mRNA expressions of α-SMA,collagen type Ⅰ,collagen type Ⅳ,TGF-β1,IL-1β,IL-6 and MCP-1 reduced in 400 mg/L PFD+HG group (all P ＜ 0.05).Conclusions PFD can inhibit high glucose-induced proliferation and activation of glomerular mesangial cells,decrease the expression of TGF-β1 and proinflammatory factors,as well as reduce the synthesis of collagen,which improve renal fibrosis of db/db mice.
