Myricetin attenuates renal fibrosis by activating Nrf2/HO-1 pathway to inhibit oxidative stress
10.16438/j.0513-4870.2023-0825
- VernacularTitle:杨梅素通过激活Nrf2/HO-1通路抑制氧化应激改善肾脏纤维化
- Author:
Dong-xue LI
;
Zhou HUANG
;
Han-yu WANG
;
Zhi-hao ZHANG
;
Ning-hua TAN
;
Xue-yang DENG
- Publication Type:Research Article
- Keywords:
myricetin;
unilateral ureteral obstruction;
common bile duct ligation;
renal fibrosis;
oxidative stress
- From:
Acta Pharmaceutica Sinica
2024;59(2):359-367
- CountryChina
- Language:Chinese
-
Abstract:
This paper investigates the effect of myricetin (MYR) on renal fibrosis induced by unilateral ureteral obstruction (UUO) and common bile duct ligation (CBDL) in mice and its mechanism. The animal experiment has been approved by the Ethics Committee of China Pharmaceutical University (NO: 2022-10-020). Thirty-five ICR mice were divided into control, UUO, UUO+MYR, CBDL and CBDL+MYR groups. H&E and Masson staining were used to detect pathological changes in kidney tissues. Western blot (WB) was used to detect the expression of fibrosis-related proteins in renal tissue, and total superoxide dismutase (SOD) activity detection kit (WST-8) was used to detect the changes of total SOD in renal tissue of CBDL mice. In vitro, HK-2 cells and transforming growth factor beta 1 (TGF-β1, 10 ng·mL-1) were used to induce fibrotic model, and high glucose (30 mmol·L-1) was used to induce oxidative stress model, and then treated with different concentrations of MYR, WB was used to detect the expression of fibrosis and oxidative stress-related proteins, while NIH/3T3 cells were treated with different concentrations of MYR, and their effects on cell proliferation were detected by 5-bromo-2′-deoxyuridine (Brdu). The results showed that the renal lesions in UUO group and CBDL group were severe, collagen deposition was obvious, the expression of collagen-Ⅰ (COL-Ⅰ), α-smooth muscle actin (α-SMA), fibronectin (FN), vimentin and plasminogen activator inhibitor-1 (PAI-1) protein was up-regulated, and the activity of SOD enzyme in CBDL group was significantly decreased. MYR partly reversed the above changes after treatment. MYR inhibited the proliferation of NIH/3T3 cells but had no effect on the proliferation of HK-2 cells, and decreased the upregulation of PAI-1, FN and vimentin in HK-2 cells stimulated by TGF-β1. MYR can also up-regulate the down-regulation of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) in HK-2 cells stimulated by high glucose. To sum up, MYR can improve renal fibrosis in vivo and in vitro, probably by inhibiting the proliferation of fibroblasts and activating Nrf2/HO-1 signal pathway to inhibit oxidative stress.
