Influences of sufentanil on inflammatory response and chondrocyte apoptosis in osteoarthritis rats by modulating Ras/Raf/MEK/ERK signaling pathway.

Objective: To investigate the influences of sufentanil (Suf) on the inflammatory response and chondrocyte apoptosis 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 cartilage 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 apoptosis 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. [ABSTRACT FROM AUTHOR]