Mechanism of Tangbikang Dry Paste in Prevention and Treatment of Type 2 Diabetic Peripheral Neuropathy Based on GLO-1/AGE/RAGE Pathway
10.13422/j.cnki.syfjx.20242425
- VernacularTitle:基于GLO-1/AGE/RAGE通路探讨糖痹康干膏防治2型糖尿病周围神经病变的作用机制
- Author:
Lijia WU
1
;
Chengfei ZHANG
2
;
Xiaolei JIA
3
;
Lingling QIN
1
;
Haiyan WANG
1
;
Yukun HUANG
4
;
You WANG
1
;
Xincui BAO
1
;
Jing YANG
1
;
Cuiyan LYU
5
;
Tonghua LIU
1
Author Information
1. Beijing University of Chinese Medicine， Beijing 100029， China
2. Dongfang Hospital of Beijing University of Chinese Medicine， Beijing 100071， China
3. Beijing University of Chinese Medicine Third Affiliated Hospital， Beijing 100029， China
4. Xiamen Susong Hospital， Xiamen 361000， China
5. Beijing Hospital of Traditional Chinese Medicine， Capital Medical University， Beijing 100010， China
- Publication Type:Journal Article
- Keywords:
type 2 diabetic peripheral neuropathy （DPN）;
Tangbikang dry paste;
glyoxalase-1 （GLO-1）;
advanced glycation end products （AGE）;
receptor for advanced glycation end products （RAGE）
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(11):60-69
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the mechanism of Tangbikang dry paste in the prevention and treatment of type 2 diabetic peripheral neuropathy （DPN） based on the glyoxalase-1 （GLO-1）/advanced glycation end products （AGE）/receptor for advanced glycation end products （RAGE） pathway. MethodsA total of 56 Sprague-Dawley rats were randomly divided， with eight assigned to the normal group. The remaining 48 rats were fed a high-fat diet combined with intraperitoneal injection of streptozotocin （STZ） to induce a type 2 diabetes mellitus （T2DM） model. Based on blood glucose levels， the rats were randomly assigned to the model group， Tanglin group （13.5 mg·kg-1）， metformin group （135 mg·kg-1）， and Tangbikang dry paste low-， medium-， and high-dose groups （3， 6， 12 g·kg-1）. Successful modeling of DPN was confirmed by a decrease in mechanical pain threshold in the model group at week 4. Fasting blood glucose， body weight， and mechanical pain threshold were measured every 4 weeks. After 16 weeks of intervention， the pathological morphology of the sciatic nerve was observed using hematoxylin-eosin （HE） staining. The expression of RAGE， AGE， protein kinase C （PKC）， and collagen （COL） in the sciatic nerve was assessed by immunohistochemistry. The mRNA expression of RAGE， PKC， Toll-like receptor （TLR）， COL， and GLO-1 was detected using real-time quantitative PCR （Real-time PCR）. Serum levels of aspartate aminotransferase （AST）， alanine aminotransferase （ALT）， creatinine （CREA）， urea （UREA）， interleukin-6 （IL-6）， and tumor necrosis factor （TNF）-α were measured by enzyme-linked immunosorbent assay （ELISA）. ResultsCompared with the normal group， the model group showed significantly increased fasting blood glucose （P<0.01）， decreased body weight and mechanical pain threshold （P<0.01）， and elevated serum AST， ALT， CREA， UREA， IL-6， and TNF-α levels （P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was significantly increased （P<0.01）， while COL expression was decreased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was upregulated （P<0.01）， whereas COL and GLO-1 mRNA levels were downregulated （P<0.01）. Histological examination showed irregular nerve morphology， axonal alterations， and myelin degeneration. Compared with the model group， fasting blood glucose levels in the Tangbikang dry paste high-dose group at all time points and in the medium-dose group at weeks 4 and 16 were significantly reduced （P<0.05， P<0.01）. No significant changes in body weight were observed across all Tangbikang dose groups. The mechanical pain threshold was elevated at different time points after administration in all Tangbikang groups （P<0.05， P<0.01）. Serum IL-6 and TNF-α levels were decreased in all dose groups （P<0.05， P<0.01）. The expression of RAGE， AGE， and PKC in the sciatic nerve was reduced （P<0.01）， while COL expression was increased （P<0.01）. The mRNA expression of TLR， RAGE， and PKC was downregulated （P<0.01）， whereas GLO-1 mRNA expression was upregulated （P<0.05， P<0.01）. Additionally， COL mRNA expression was significantly increased in the low- and high-dose groups （P<0.01）. Pathological changes in the sciatic nerve were milder in all Tangbikang groups compared to the model group. ConclusionTangbikang dry paste significantly improves DPN， and its mechanism may be associated with the regulation of the GLO-1/AGE/RAGE signaling pathway.
