Effect of Modified Huangqi Guizhi Wuwutang on Stress-related IRE1α/CHOP Pathway of Sciatic Nerve Endoplasmic Reticulum in Diabetes Rats
10.13422/j.cnki.syfjx.20231329
- VernacularTitle:黄芪桂枝五物汤加减对糖尿病大鼠坐骨神经内质网应激IRE1α/CHOP通路的影响
- Author:
Yan ZHANG
1
;
Hongzhu LONG
2
;
Xipeng WANG
3
;
Weifang CAO
4
;
Lili WU
5
;
Tonghua LIU
5
;
Jingxin ZHOU
6
Author Information
1. Beijing Friendship Hospital Affiliated to Capital Medical University，Beijing 100050，China
2. China-Japan Friendship Hospital，Beijing 100029，China
3. Hospital of Beijing International Studies University，Beijing 100024，China
4. Institute of Basic Medical Sciences，Chinese Academy of Medical Sciences，Beijing 100007，China
5. School of Traditional Chinese Medicine，Beijing University of Chinese Medicine，Beijing 100029，China
6. Dongzhimen Hospital，Beijing University of Chinese Medicine，Beijing 100700，China
- Publication Type:Journal Article
- Keywords:
modified Huangqi Guizhi Wuwutang;
peripheral neuropathy in diabetes;
inositol-requiring enzyme 1α （IRE1α）;
phosphorylated inositol-requiring enzyme 1α （p-IRE1α）;
CCAAT/enhancer binding protein homologous protein
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2023;29(16):43-51
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the protective effect of modified Huangqi Guizhi Wuwutang （MHGW） on endoplasmic reticulum stress in the sciatic nerve of diabetes rats based on the pathways of inositol-requiring enzyme 1α （IRE1α） and CCAAT/enhancer-binding protein homologous protein （CHOP）. MethodSixty rats were fed on a high-sugar and high-fat diet for six weeks， followed by intraperitoneal injection of streptozotocin at a dose of 35 mg·kg-1. Random blood glucose levels were measured three days later and rats with a sustained blood glucose level ≥ 16.7 mmol·L-1 were included in study （n=48）. The rats were randomly divided into a model group， an α-lipoic acid group （0.026 8 g·kg-1·d-1）， a high-dose MHGW group （2.5 g·kg-1·d-1）， and a low-dose MHGW group （1.25 g·kg-1·d-1）. Another 10 rats were assigned to the normal group. The intervention lasted for 16 weeks. After 16 weeks， the sciatic nerve structure of the rats in each group was observed under light microscopy using Luxol fast blue （LFB） staining. Transmission electron microscopy was used to observe the ultrastructure of the sciatic nerve. Chemiluminescence method was employed to measure the serum reactive oxygen species （ROS） levels. Western blot and real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） were used to evaluate the expression of p-IRE1α protein， IRE1α mRNA， CHOP protein， and CHOP mRNA in the sciatic nerve of the rats. ResultCompared with the normal group， the model group showed elevated serum ROS levels （P<0.01）. In contrast， the serum ROS levels were significantly reduced in the treatment groups compared with those in the model group （P<0.01）. The sciatic nerve of the model group showed pathological changes compared with that in the normal group， while the treatment groups exhibited improvement in sciatic nerve pathology compared with the model group. The protein expression of p-IRE1α and CHOP in the sciatic nerve significantly increased in the model group as compared with that in the normal group （P<0.01）. However， the treatment groups showed a significant decrease in the protein expression of p-IRE1α and CHOP in the sciatic nerve compared with the model group （P<0.05， P<0.01）. Furthermore， compared with the normal group， the model group showed upregulated mRNA expression of IRE1α and CHOP in the sciatic nerve （P<0.01）， while the treatment groups exhibited a significant decrease in the mRNA expression of IRE1α and CHOP compared with the model group （P<0.01）. ConclusionMHGW can alleviate endoplasmic reticulum stress-induced cell apoptosis and improve the structure and function of the sciatic nerve in diabetes rats by inhibiting the expression of IRE1α/CHOP pathway-related proteins and mRNA， thereby preventing and treating peripheral neuropathy in diabetes.
