Effect of Modified Shengjiangsan on Oxidative Stress and Apoptosis in MN Rats via Regulating HIF-1α/NOX4 Signaling Pathway
10.13422/j.cnki.syfjx.20211937
- VernacularTitle:加味升降散调控HIF-1α/NOX4信号通路对膜性肾病大鼠氧化应激和凋亡的影响
- Author:
Shao-hui LI
1
;
Fei GAO
1
;
Wen-xia HAO
1
;
Miao TAN
2
;
Feng-wen YANG
3
;
Su-zhi CHEN
3
;
Jin-chuan TAN
3
Author Information
1. Hebei University of Chinese Medicine，Shijiazhuang 050200，China
2. The Fourth Hospital of Hebei Medical University， Shijiazhuang 050000， China
3. The First Affiliated Hospital of Hebei University of Chinese Medicine， Shijiazhuang 050011，China
- Publication Type:Research Article
- Keywords:
membranous nephropathy;
oxidative stress;
apoptosis;
hypoxia-inducible factor-1α （HIF-1α）/nicotinamide adenine dinucleotide phosphate oxidase 4 （NOX4） signaling pathway;
modified Shengjiangsan
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2021;27(19):66-72
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the intervention effect of modified Shengjiangsan on hypoxia-inducible factor-1α （HIF-1α）/nicotinamide adenine dinucleotide phosphate oxidase 4 （NOX4） signaling pathway in membranous nephropathy （MN） rats and to explore its mechanism to reduce oxidative stress and apoptosis in renal tissues. Method:Cationized bovine serum albumin （C-BSA） was injected into the tail vein of rats to replicate the MN model. Rats were randomly divided into a model group， a modified Shengjiangsan group， and a benazepril group after modeling， and administered by gavage once a day accordingly. At the end of the 4th week， the 24-h urine total protein （UTP）， urea nitrogen （BUN）， and serum creatinine （SCr） levels of each group were detected. Enzyme-linked immunosorbent assay（ELISA）was used to detect the levels of superoxide dismutase （SOD）， malondialdehyde （MDA）， and reactive oxygen species （ROS） in renal tissues of rats. In situ end labeling（TUNEL） staining was used to detect the cell apoptosis rate. The mRNA and protein expression levels of HIF-1α and NOX4 were detected by real-time fluorescence-based quantitative polymerase chain reaction（Real-time PCR）and Western blot， respectively. The immunohistochemistry method was used to detect the protein expression levels of B-cell lymphomas -2 （Bcl-2）， B-cell lymphomas xl （Bcl-xl）， Bcl-2 associated X protein （Bax）， Bcl-2 cell death regulator antibody （Bim）. Result:Compared with the normal group， the model group showed increased UTP （P<0.05）， decreased SOD， elevated MDA and ROS （P<0.05）， up-regulated mRNA and protein expression of HIF-1α and NOX4 （P<0.05）， enhanced protein expression of Bax and Bim， declining protein expression of Bcl-xl and Bcl-2 （P<0.05）， and increased cell apoptosis in renal tissues. Compared with the model group， the modified Shengjiangsan group and the benazepril group displayed declining UTP （P<0.05）， up-regulated SOD， decreased MDA and ROS （P<0.05）， down-regulated mRNA and protein expression of HIF-1α and NOX4 （P<0.05）， diminished protein expression of Bax and Bim， elevated protein expression of Bcl-xl and Bcl-2 （P<0.05）， and reduced cell apoptosis in renal tissues （P<0.05）. Conclusion:The protective effect of modified Shengjiangsan on the kidney is presumedly achieved by reducing the oxidative stress and apoptosis in renal tissues of MN rats via inhibiting the HIF-1α/NOX4 signaling pathway.
