Effect of Modified Shengjiangsan on Renal Endoplasmic Reticulum Stress and Sirt1/PERK Pathway in Rat Model of Diabetic Nephropathy
10.13422/j.cnki.syfjx.20240340
- VernacularTitle:加味升降散对糖尿病肾病大鼠肾脏内质网应激和Sirt1/PERK通路的影响
- Author:
Meifang REN
1
;
Zhenhua WU
1
;
Fei GAO
2
;
Guodong YUAN
1
;
Qian ZHANG
1
;
Xiaoling GUO
1
;
Fengwen YANG
1
Author Information
1. The First Affiliated Hospital of Hebei University of Chinese Medicine， Shijiazhuang 050011， China
2. Dongzhimen Hospital of Beijing University of Chinese Medicine， Beijing 100700， China
- Publication Type:Journal Article
- Keywords:
modified Shengjiangsan;
diabetic nephropathy;
podocyte injury;
oxidative stress;
endoplasmic reticulum stress;
silent information regulator 1 （Sirt1）/protein kinase RNA-like endoplasmic reticulum kinase （PERK） pathway
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(14):55-62
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the molecular mechanism of modified Shengjiangsan in alleviating endoplasmic reticulum （ER） stress and reducing urinary protein in the rat model of diabetic nephropathy （DN）. MethodSeventy-five SD rats were randomized into normal， model， low-， medium-， and high-dose （4.37， 8.73， 17.46 g·kg-1， respectively） modified Shengjiangsan， and irbesartan （0.014 g·kg-1） groups， with 10 rats in each group. Rats were administrated with corresponding doses of medications or distilled water by gavage， once a day， for 8 consecutive weeks. After the last administration， the levels of glucose （GLU） in the blood， 24-hour urinary protein （24 h-UTP）， and superoxide dismutase （SOD）， malondialdehyde （MDA）， and glutathione peroxidase （GSH-Px） in the renal tissue were measured. Hematoxylin-eosin staining， periodic acid-Schiff staining， and transmission electron microscopy were employed to observe the pathological changes in rat kidneys. Immunohistochemistry was employed to measure the expression levels of nephrin， podocin， glucose-regulated protein 78 （GRP78）， C/EBP homologous protein （CHOP）， and activating transcription factor 4 （ATF4） in the kidneys of rats. Western blot was employed to measure the protein levels of silent information regulator 1 （Sirt1）， phosphorylated （p）-protein kinase RNA-like endoplasmic reticulum kinase （PERK）， and p-eukaryotic translation initiation factor 2 alpha （eIF2α） in rat kidneys. ResultCompared with the normal group， the modeling caused pathological damage to the kidneys， elevated the levels of GLU and 24 h-UTP （P<0.05）， up-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and down-regulated the protein level of Sirt1 （P<0.05） in rat kidneys. Compared with the model group， modified Shengjiangsan and irbesartan lowered the GLU and 24 h-UTP levels （P<0.05）， alleviated the pathological damage in the renal tissue， down-regulated the protein levels of GRP78， CHOP， ATF4， p-PERK， and p-eIF2α （P<0.05）， and up-regulated the protein level of Sirt1 （P<0.05）. ConclusionModified Shengjiangsan up-regulates Sirt1 expression and inhibits phosphorylation of proteins in the PERK/eIF2α pathway to reduce ER stress and oxidative stress in the renal tissue， thus alleviating the pathological damage in the renal tissue and reducing urinary protein in DN rats.
