GDL Alleviate Liver Fibrosis in Rats with Copper-Loaded Wilson's Disease By Regulating Autophagy Through LncRNA Meg3
10.11969/j.issn.1673-548X.2025.01.008
- VernacularTitle:肝豆灵通过lncRNA Meg3调控自噬减轻铜负荷Wilson病大鼠肝纤维化
- Author:
Xin YIN
1
;
Han WANG
;
Lanting SUN
Author Information
1. 230031 合肥,安徽中医药大学第一临床医学院
- Publication Type:Journal Article
- Keywords:
GDL;
LncRNA Meg3;
Autophagy;
Hepatic fibrosis
- From:
Journal of Medical Research
2025;54(1):37-42
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression of long non-coding RNA maternally expressed gene 3(lncRNA MEG3)and autophagy in the liver of copper-loaded rats treated with Gandouling(GDL)and to explore its mechanism of action in attenuating liver fi-brosis.Methods Ten SD rats were taken as the normal group,and another 50 were divided into model groups,penicillamine group,GDL low dose group,GDL medium dose group,and GDL high dose group,with 10 rats in each group.The liver fibrosis model of rats with copper-loaded Wilson's Disease was established by gavage of copper sulphate pentahydrate.HE and Masson's staining were used to observe liver pathological morphology.ELISA was used to detect the levels of hyaluronic acid(HA),and laminin(LN),type Ⅲ procol-lagen(PC-Ⅲ),and type Ⅳ collagen(C-Ⅳ).A biochemical kit was used to detect the activity of alanine aminotransferase(ALT)and azelaic acid aminotransferase(AST).Western blot was used to detect the expression of alpha-smooth muscle actin(α-SMA)and collagen type Ⅰ(Col-Ⅰ).RT-qPCR was used to detect the expression of Beclin-1 and lncRNA Meg3mRNA.Immunofluorescence was used to detect the expression of Beclin-1 and LC3-Ⅱ.Results Compared with the normal group,rats in the model group showed collagen fiber deposition in liver tissue,increased levels of HA,LN,PC-Ⅲ,C-Ⅳ,α-SMA,Col-Ⅰ,liver injury,decreased ex-pression of lncRNA Meg3,and increased levels of key markers of autophagy,Beclin-1 and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ).After administration of GDL and penicillamine,comparing to the model groups,the levels of AST,LN,Col-Ⅰ,and Beclin-1 showed a trend of reduction in both GDL low,medium,and high dose groups and penicillamine group(P＜0.01).The levels of C-Ⅳ,and α-SMA were decreased in the GDL medium,low,and high dose group and the penicillamine group,with a significant re-duction in the GDL medium and high dose group(GDL low dose group:P＜0.05,GDL middle-high dose group:P＜0.01).Moreover,the reduced expression of lncRNA Meg3 was reversed,and the level of lncRNA Meg3 was increased in the GDL middle-high dose group and the penicillamine group(P＜0.01).Pathological section results indicated that the degree of liver fibrosis was reduced in rats after GDL intervention,and the effect of GDL was obvious in the high dose group.Conclusion GDL alleviated liver fibrosis,and the mecha-nism may be related to the regulation of autophagy expression by lncRNA Meg3.
