miR-210 agonist alleviates renal inflammatory response and fibrosis in diabetic kidney disease rats
10.3760/cma.j.cn441217-20200314-00149
- VernacularTitle:miR-210激动剂减轻糖尿病肾脏病大鼠肾脏炎性反应和纤维化
- Author:
Lixia XIAO
1
;
Ruiqiong KE
;
Yang WANG
;
Shihua HONG
;
Weiming LYU
;
Xunhua LIU
Author Information
1. 赣南医学院第一附属医院内分泌科，赣州 341000
- From:
Chinese Journal of Nephrology
2020;36(11):858-865
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective effect and mechanism of microRNA-210 agonist (agomiR-210) on kidney in diabetic kidney disease (DKD) rats.Methods:Thirty-six 5-week-old male SD rats were divided into normal control (NC) group, agomiR-NC control group, agomiR-210 control group, DKD model group, DKD+agomiR-NC group and DKD+agomiR-210 group, with 6 rats in each group. Diabetic rats were established by a high-fat diet combined with intraperitoneal injection of streptozotocin (STZ), then were fed for 12 consecutive weeks to construct DKD model rats. During 2nd-4th week of continuous feeding, the rats in DKD+agomiR-210 group were injected with 20 nmol/kg agomiR-210 via tail vein twice a week. Blood glucose levels, 24 h urine albumin (Alb) and 24 h urine microalbumin (MAU) contents were measured regularly. At the end of the 12th week, the rats were sacrificed, and renal tissues were collected. The renal histopathological changes were assessed by HE, PAS and Masson staining methods. The mRNA and protein expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6 in renal tissues were detected by RT-qPCR and Western blot. The distributions and expressions of α-smooth muscle actin (α-SMA), typeⅠ collagen (Col-Ⅰ), type Ⅳ collagen (Col-Ⅳ) and fibronectin (FN) in renal tissues were detected by immunohistochemical method. The protein expression levels of phospho(p)-Smad3 and p-NF-κB p65 in renal tissues were detected by Western blot and immunohistochemical methods.Results:Compared with DKD model group, the renal pathological damages in DKD+agomiR-210 group were improved, the blood glucose level, glycogen deposition and collagen accumulation were significantly decreased (all P<0.05), the urinary excretions of Alb and MAU were significantly reduced (all P<0.01), and the expressions of TNF-α, IL-1β, IL-6, α-SMA, Col-Ⅰ, Col-Ⅳ, FN, p-Smad3 and p-NF-κB p65 in renal tissues were significantly decreased (all P<0.01). Conclusion:AgomiR-210 can alleviate renal pathological changes and urinary Alb and MAU excretion in rats with DKD, which may be related to its inhibition of Smad3 and NF-κB activity.
