Abstract: Objective To investigate the effects and mechanism of midazolam (MDZ) on cartilage damage and pain in a rat model of osteoarthritis (OA) induced by monosodium iodoacetate (MIA). Methods OA rat models were divided into following groups: OA, low, medium, and high-dose MDZ (30, 60, 90 mg/kg), high-dose MDZ+compound C (0.2 mg/kg via tail vein) and control group with in each. Behavioral performance was assessed using the modified Lequesne MG scale. Joint pain was measured, and level of MMP-1, COX-2, and IL-1 in joint fluid was measured by ELISA method. Cartilage damage was examined by histology with Van Gieson and toluidine blue staining microscopy. AMPK/SIRT1/NF-κB pathway related proteins were detected by Western blot. Results OA rats showed superficial cartilage staining loss, thinning of cartilage layers, and incomplete tide lines. MDZ groups showed reduced cartilage damage, but more significant damage in the MDZ-H+compound C group. OA rats had higher Lequesne and Mankin scores, MMP-1, COX-2, IL-1 levels, and p-NF-κB p65 expression, while p-AMPK/AMPK and SIRT1 were all decreased (P＜0.05). MDZ treatments decreased these scores and markers dose-dependently, with some reversal trends seen in the MDZ-H+compound C group. Conclusions MDZ can partially activate the AMPK/SIRT1/NF-κB signaling pathway, thereby alleviating cartilage damage and pain in rats with OA.

Key words: midazolam, adenosine monophosphate activated protein kinase/silent information regulator 1/nuclear factor-kappa B, monosodium iodoacetate, osteoarthritis, cartilage injury