Regulatory Effect of Gandou Decoction on Wnt/β-catenin Signaling Pathway in Liver of Wilson Model Copper-loaded Rats
10.13422/j.cnki.syfjx.20190403
- VernacularTitle: 肝豆汤对Wilson病模型铜负荷大鼠肝脏Wnt/β-catenin信号通路的调控作用
- Author:
Hao GENG
1
;
Hai LI
2
;
Chen-chen XU
3
;
Jian-jian DONG
3
;
Yan CHEN
4
;
Yong-zhu HAN
3
;
Yong-sheng HAN
3
;
Ren-min YANG
3
;
Nan CHENG
3
Author Information
1. Graduate School, Anhui University of Chinese Medicine, Hefei 230038, China
2. Hospital of Armed Police Force of Anhui Province, Hefei 230041, China
3. Hospital Affiliated to Neurological Institute, Anhui University of Chinese Medicine, Hefei 230061, China
4. Hospital of University of Science and Technology of China, Hefei 230000, China
- Publication Type:Research Article
- Keywords:
Wilson disease;
Gandou decoction;
Wnt/β-catenin signaling pathway;
hepatic injury
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2019;25(7):75-81
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the regulatory effect of Gandou decoction (GDD) on Wnt/β-catenin signaling pathway in hepatic tissue of Wilson disease model copper-loaded rats and its potential mechanism. Method: One hundred and fifteen SD rats were randomly divided into the normal group (n=20) and modeling group. Modeling group was given copper sulfate feed (1 g·kg-1·d-1) and 0.185%copper sulfate solution (0.02 mL·g-1·d-1) for 12 weeks after one week's adaptive feeding, so as to build the copper loaded rats model. After modeling, 95 model rats were randomly divided into model group (n=45), which were fed by modeling method for continuously four weeks; GDD group and penicillamine (PCA) group (n=25 per group). GDD group and PCA group were given GDD(0.4 g·kg-1·d-1) and PCA (0.09 g·kg-1·d-1) by gavage for four weeks. The hepatic tissues of rats in each group were removed after final medication for further research:inductively coupled plasma-atomic emission spectrometry(ICP-AES) was used to detect the content of Cu element in rat livers. Htoxylin eosin(HE) staining was used to detect the pathological changes of rat liver. Immunohistochemistry was used to detect expression of oxidative stress. Western blot was used to detect protein expressions in Wnt/β-catenin of rat livers. Result: Compared with model group, content of Cu element in GDD group was less (P<0.05); compared with model group, content of Cu element in PCA group was less (P<0.01). The hepatic cells of model group showed different sizes, disordered arrangement and partial loss of hepatic cord compared with normal group; the hepatic injuries of GDD and PCA group were significantly lower than model group.Compared with model group, 8-Hydroxyguanosine, Nitrotyrosine protein positive expression in GDD and PCA group were significantly less (P<0.01). Compared with model group, the expression quantities of β-catenin, p-glycogen synthase kinase-3β(p-GSK3β),cellular myelocytomatosis oncogene (c-Myc) in GDD and PCA group increased, while p-β-catenin, Dishevelled3, GSK3β protein expressions reduced (P<0.01). Conclusion: GDD can relieve liver damage by promoting excessive copper discharge. GDD decoction can promote the compensatory self-healing of the injured liver tissue by activating Wnt/β-catenin signaling pathway in the hepatic tissue of Wilson disease model copper-loaded rats, so as to reduce the therapeutic effect of hepatocellular injury induced by high copper.
