Effects of Qizhi Tongluo Granules on Endoplasmic Reticulum Stress and Nrf2/OASL1 Signaling Pathway in Rats with Membranous Nephropathy
10.13422/j.cnki.syfjx.20260138
- VernacularTitle:芪蛭通络颗粒对膜性肾病大鼠内质网应激及Nrf2/OASL1信号通路的影响
- Author:
Qin LU
1
;
Fei GAO
2
;
Xiaomeng WANG
1
;
Zhenhua WU
1
;
Guodong YUAN
1
;
Fengwen YANG
1
;
Jinchuan TAN
1
Author Information
1. Hebei University of Chinese Medicine，Shijiazhuang 050011，China
2. Chaoyang District Traditional Chinese Medicine Hospital，Beijing 100020，China
- Publication Type:Journal Article
- Keywords:
Qizhi Tongluo granules;
membranous nephropathy;
podocyte injury;
oxidative stress;
endoplasmic reticulum stress;
nuclear factor erythroid 2-related factor 2 （Nrf2）/2'-5' oligoadenylate synthetase-like protein 1 （OASL1） signaling pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(13):134-143
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the therapeutic efficacy of Qizhi Tongluo granules on proteinuria in membranous nephropathy （MN） and its potential protective effects and underlying mechanism against endoplasmic reticulum stress. MethodsAfter 70 Sprague-Dawley （SD） rats were adaptively fed for one week， the MN rat model was established by injecting cationic bovine serum albumin （C-BSA） into the tail vein. Rats were divided into the normal group， model group， low-dose Qizhi Tongluo granules group （2.43 g·kg-1）， medium-dose group （4.86 g·kg-1）， high-dose group （9.72 g·kg-1）， and benazepril group （0.01 g·kg-1）， with 10 rats in each group. Treatment was administered for four weeks. The 24-hour urinary total protein （UTP） content， as well as the levels of reactive oxygen species （ROS）， malondialdehyde （MDA）， and glutathione peroxidase （GPX） in renal tissues， were measured. Renal pathological changes were assessed using immunoglobulin G （IgG） staining， periodic acid-silver methenamine （PASM） staining， and transmission electron microscopy （TEM）. The localization and expression levels of glucose-regulated protein 78 （GRP78）， phosphorylated inositol-requiring enzyme 1α （p-IRE1α）， phosphorylated protein kinase R-like endoplasmic reticulum kinase （p-PERK）， activating transcription factor 4 （ATF4）， nuclear factor erythroid 2-related factor 2 （Nrf2）， and 2'-5' oligoadenylate synthetase-like protein 1 （OASL1） in rat kidneys were detected by immunohistochemistry （IHC）. The mRNA and protein expression levels of Nrf2， thioredoxin 1 （Trx1）， thioredoxin-interacting protein （TXNIP）， and OASL1 in rat kidneys were measured using real-time quantitative polymerase chain reaction （Real-time PCR） and Western blot analysis. ResultsCompared with the normal group， UTP levels were significantly increased in the model rats （P<0.05）， with obvious renal pathological damage. GPX content levels were significantly decreased in renal tissue （P<0.05）， while ROS and MDA content levels were significantly increased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins was significantly increased in the kidneys （P<0.05）， while the mRNA and protein expression levels of Trx1 and Nrf2 were significantly decreased （P<0.05）. The mRNA and protein expression levels of TXNIP and OASL1 were significantly increased （P<0.05）. Compared with the model group， the UTP levels of rats in the Qizhi Tongluo granules groups and the benazepril group decreased to varying degrees （P<0.05）， and renal pathological damage was significantly alleviated. The GPX content in renal tissue was significantly increased （P<0.05）， while the ROS and MDA levels were significantly decreased （P<0.05）. The expression of GRP78， p-IRE1α， p-PERK， and ATF4 proteins in the kidney was significantly decreased （P<0.05）. The mRNA and protein expression levels of Trx1 and Nrf2 were significantly increased （P<0.05）， while the mRNA and protein expression levels of TXNIP and OASL1 were significantly decreased （P<0.05）. ConclusionQizhi Tongluo granules alleviates proteinuria in MN rats by modulating the Nrf2/OASL1 signaling pathway in renal tissues to reduce endoplasmic reticulum stress， which represents its underlying mechanism.
