Effect of butorphanol on apoptosis of human articular chondrocytes induced by IL-1β by regulating HMGB1-RAGE signal pathway
10.3969/j.issn.1000-484X.2025.08.023
- VernacularTitle:布托啡诺调节HMGB1-RAGE信号通路对IL-1β诱导的人关节软骨细胞凋亡的影响
- Author:
Kai LIU
1
;
Tiantian ZHANG
1
;
Yang HAN
1
Author Information
1. 滕州市中心人民医院麻醉科,枣庄 277500
- Publication Type:Journal Article
- Keywords:
Butorphanol;
HMGB1-RAGE;
IL-1β;
Human articular chondrocytes;
Apoptosis
- From:
Chinese Journal of Immunology
2025;41(8):1933-1939
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate effect of butorphanol on apoptosis of human articular chondrocytes induced by IL-1β by regulating HMGB1-RAGE signal pathway.Methods:Human articular chondrocytes were cultured in vitro,CCK-8 method was applied to determine survival rate of human articular chondrocytes before and after induction of 10 ng/ml IL-1β treated with 0,1,2,4,6 and 8 μmol/L butorphanol,optimal concentration of butorphanol was selected.Human articular chondrocytes were cultured in vitro and randomly separated into control group,IL-1β group,IL-1β+butorphanol group,IL-1β+empty group and IL-1β+butorphanol+HMGB1 overexpression group,except control group,other groups were induced with 10 ng/ml IL-1β to establish an cell model of osteoarthritis(OA)in vitro,after grouping and treatment of butorphanol and plasmid,CCK-8 and EdU staining were applied to detect cell prolife-ration in each group;flow cytometry was applied to detect cell apoptosis in each group;2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe was applied to detect ROS content of human articular chondrocytes in each group;ELISA was applied to detect levels of inflammatory related factors IL-6,TNF-α and IL-18 in each group;kits were applied to detect activity levels of cell antioxidant enzymes catalase(CAT),superoxide dismutase(SOD),glutathione peroxidase(GSH-Px)in each group;Western blot was applied to detect expressions of apoptotic proteins(Bax,Cleaved Caspase-3)and HMGB1-RAGE pathway related proteins in each group.Results:Compared with control group,survival rate,proliferation rate,CAT,SOD,GSH-Px levels of human articular chondrocytes in IL-1β group were obviously reduced(P<0.05),apoptosis rate,relative ROS content,IL-6,TNF-α and IL-18 produc-tion levels,Bax,Cleaved Caspase-3,HMGB1 and RAGE protein expressions were obviously increased(P<0.05).Compared with IL-1β group,survival rate,proliferation rate,CAT,SOD,GSH-Px levels of human articular chondrocytes in IL-1β+butorphanol group were obviously increased(P<0.05),apoptosis rate,relative ROS content,IL-6,TNF-α and IL-18 production levels,Bax,Cleaved Caspase-3,HMGB1 and RAGE protein expressions were obviously reduced(P<0.05);there was no obvious change in all indicators in IL-1β+empty group(P>0.05).Compared with IL-1β+butorphanol group,survival rate,proliferation rate,CAT and SOD,GSH-Px levels of human articular chondrocytes in IL-1β+butorphanol+HMGB1 overexpression group were obviously reduced(P<0.05),apoptosis rate,relative ROS content,IL-6,TNF-α and IL-18 production levels,Bax,Cleaved Caspase-3,HMGB1 and RAGE protein expressions were obviously increased(P<0.05).Conclusion:Butorphanol can alleviate IL-1β induced inflammation of human articular chondrocytes,enhance its antioxidant activity,thereby inhibit chondrocyte apoptosis by reducing HMGB1-RAGE signaling activity.