Effect of evodiamine on cartilage damage in knee osteoarthritis model rats by regulating the Shh/Gli1 signaling pathway
10.12007/j.issn.0258-4646.2024.09.011
- VernacularTitle:吴茱萸碱调节Shh/Gli1信号通路对膝骨关节炎大鼠软骨损伤的影响
- Author:
Shijuan TU
1
;
Hongya YANG
;
Tao LI
;
Xuemei LIANG
Author Information
1. 成都中医药大学基础医学院病原生物学与免疫学教研室,成都 610075
- Keywords:
knee osteoarthritis;
cartilage injury;
evodiamine;
Shh/Gli1 signaling pathway
- From:
Journal of China Medical University
2024;53(9):827-833
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effect of evodiamine(Evo)on cartilage damage in knee osteoarthritis(KOA)model rats and analyze its mechanism of action.Methods Sixty rats were randomly divided into control,model,low-dose Evo,medium-dose Evo,high-dose Evo,and activator(Shh/Gli1 signaling pathway activator purmorphamine)+high-dose Evo groups,with 10 rats per group.A rat KOA model was constructed,and the corresponding drug interventions were administered to each group.Behavioral observations and Lequesne MG scores were conducted among rats in each group.Hematoxylin&eosin staining and safranine O-fixed green staining were applied to observe the pathological changes and Mankin score of rat cartilage tissue.Enzyme linked immunosorbent assays(ELISA)were applied to detect the levels of interleukin-1β(IL-1β),IL-18,and tumor necrosis factor-α(TNF-α),while dUTP nick end labeling was applied to detect chondrocyte apoptosis.Immunohistochemistry was applied to detect the expression of type Ⅱ collagen(CⅡ)and matrix metalloproteinase 13(MMP13)proteins,and Western blotting was applied to detect the expression of Shh,Smo,Ptc1,and Gli1 proteins.Results The rats in the model group showed movement disorders and severe cartilage tissue damage compared with the control group.The Lequesne MG score,Mankin score,IL-1β,IL-18,and TNF-α levels,chondrocyte apoptosis rate,MMP13 protein expression,and Shh,Smo,Ptc1,and Gli1 protein levels obviously increased,while the CⅡ protein expression decreased(P<0.05)compared with the model group.The activity disorders and cartilage tissue damage in rats in the low,medium,and high dose Evo groups were alleviated,the Lequesne MG score,Mankin score,IL-1β,IL-18,TNF-α levels,chondrocyte apoptosis rate,MMP13 protein expression,and Shh,Smo,Ptc1,and Gli1 protein levels were obviously decreased,the CⅡprotein expression increased(P<0.05);while the Shh/Gli1 signaling pathway activator reversed the improvement effect of high-dose Evo on cartilage damage in KOA rats.Conclusion Evodiamine may reduce the inflamma-tory response and chondrocyte apoptosis in KOA rats by inhibiting the Shh/Gli1 signaling pathway,thereby improving cartilage damage.