Discussion on the effects and mechanism of triptolide in bone destruction in collagen-induced arthritis rats based on Caspase-1/GSDMD pathway
10.3760/cma.j.cn115398-20230602-00020
- VernacularTitle:基于Caspase-1/GSDMD通路探讨雷公藤甲素抗胶原诱导性关节炎大鼠骨破坏作用
- Author:
Ruini LIU
1
;
Zixiang ZHENG
;
Yuanhao WU
Author Information
1. 天津中医药大学，天津 301617
- Keywords:
Triptolide;
Arthritis, experimental;
Bone destruction;
Pyroptosis;
Rats
- From:
International Journal of Traditional Chinese Medicine
2024;46(6):731-736
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To discuss the effects and mechanism of triptolide regulating Caspase1/GSDMD pathway in bone destruction in collagen-induced arthritis rats.Methods:The rats were divided into blank group, model group, triptolide group, and methotrexate group using a random number table method, with 5 rats in each group. Except for the blank group, all other groups were injected with bovine typeⅡ collagen at the tail root to establish an arthritis model. After 7 days of strengthening immunity, the dosage of triptolide A was calculated based on the body surface area in rats, and the triptolide A group was orally administered with triptolide A for 18 μg/kg, 1 d/time; the methotrexate group received intraperitoneal injection of 0.3 mg/kg methotrexate for 3 days per dose, with continuous intervention for 15 days. The arthritis index (AI) score and toe volume changes of the rats were recorded. The ankle joint histological changes were observed with HE staining, and the ankle joint cartilage and bone changes were observed with ferruginine solid green staining. The contents of IL-18 and IL-1β in serum were determined by ELISA. The mRNA levels of GSDMD, Caspase-1, OPG and RANKL in ankle joints were detected by real-time quantitative PCR. The expressions of GSDMD, Caspase-1, OPG and RANKL in ankle tissues were detected by Western blot.Results:After 1 and 2 weeks of administration, compared with the model group, the AI scores and toe volume values of the triptolide group, and methotrexate group decreased ( P<0.01); in the model group, a large number of inflammatory cell infiltration, synovial pannus formation, and blurred defects of the tide line of cartilage and bone staining were observed. The inflammatory infiltration, synovial pannus formation, articular cartilage and bone destruction were improved to varying degrees in each administration group. Compared with model group, serum IL-18 and IL-1β contents in triptolide group and methotrexate group significantly decreased ( P<0.01), mRNA and protein expressions of GSDMD, Caspase-1 and RANKL decreased ( P<0.01), and mRNA and protein expression of OPG increased ( P<0.01). Conclusion:Triptolide can effectively improve joint inflammation and bone destruction in collagen-induced arthritis rats, and its mechanism may be related to down-regulating the expressions of GSDMD, Caspase-1 and RANKL, and up-regulating the expression of OPG.
