中国免疫学杂志2024，Vol.40Issue(10)：2071-2075,2082,6.DOI:10.3969/j.issn.1000-484X.2024.10.009
舒芬太尼调节Ras/Raf/MEK/ERK信号通路对骨关节炎大鼠炎症反应和软骨细胞凋亡的影响
Influences of sufentanil on inflammatory response and chondrocyte apoptosis in osteoarthritis rats by modulating Ras/Raf/MEK/ERK signaling pathway
摘要
Abstract
Objective:To investigate the influences of sufentanil(Suf)on the inflammatory response and chondrocyte apopto-sis in rats with osteoarthritis(OA)by modulating Ras/Raf/mitogen-activated protein kinase kinase(MEK)/extracellular signal-regulated kinase(ERK)signaling pathway.Methods:SD rats were grouped into normal control group(NC group),blank control group(Blank group),low-dose Suf group(Suf-L group,1 μg/kg),high-dose Suf group(Suf-H group,5 μg/kg),Diacerein group(DC group,54 mg/kg),and Suf-H+ML-099(Ras/Raf/MEK/ERK pathway activator)group(5 μg/kg Suf+11.7 mg/kg ML-099),with 12 rats in each group.Except for the NC group,the other groups were all constructed OA rat models by transection of the medial meniscus tibial ligament of the right knee joint.After the modeling was successful,the corresponding drug treatment was carried out,and the rats in the NC group and the Blank group were intraperitoneally injected and gavaged with the same amount of normal saline,administer once a day for 3 weeks.Twenty-four hours after the last administration,the changes of tenderness threshold and thermal pain threshold of rats were monitored;serum levels of TNF-α,IL-1β and IL-6 were detected by ELISA;Safranin O-Fast green staining was used to detect the pathological changes of cartilage tissue;TUNEL staining was used to detect chondrocyte apoptosis;Western blot was used to detect the expressions of Ras/Raf/MEK/ERK signaling pathway protein and matrix metalloproteinase 13(MMP-13)protein in carti-lage tissue.Results:Compared with NC group,the tenderness threshold and heat pain threshold of rats in Blank group were decreased(P<0.05),and the pathological injury of cartilage tissue was serious,TNF-α,IL-1β,IL-6 levels,Mankin score,chondrocyte apopto-sis rate,Ras,Raf,MEK,p-ERK1/2,MMP-13 protein expressions were increased(P<0.05);compared with the Blank group,the change trends of the corresponding indicators in Suf-L group,Suf-H group and DC group were opposite to the above(P<0.05);ML-099 attenuated the effect of high dose Suf on OA rats.Conclusion:Suf may attenuate the inflammatory response and chondrocyte apoptosis in OA rats by inhibiting the Ras/Raf/MEK/ERK signaling pathway.关键词
舒芬太尼/骨关节炎/炎症/Ras/Raf/丝裂原激活蛋白激酶激酶/细胞外信号调节激酶信号通路Key words
Sufentanil/Osteoarthritis/Inflammation/Ras/Raf/mitogen-activated protein kinase kinase/extracellular signal-regulated kinase signaling pathway分类
医药卫生引用本文复制引用
张洪远,张腾,杜建国,陶宏..舒芬太尼调节Ras/Raf/MEK/ERK信号通路对骨关节炎大鼠炎症反应和软骨细胞凋亡的影响[J].中国免疫学杂志,2024,40(10):2071-2075,2082,6.基金项目
徐州医科大学附属医院发展基金项目(XYFM2020046). （XYFM2020046）
