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Chengneng FAN, Jintao SHI, Shuangwei LU, Meng YU. Propofol Modulates the miR-142-3p/RAC1/NF-κB Axis to Influence Knee Osteoarthritis in Rats[J]. Journal of Kunming Medical University.
Citation: Chengneng FAN, Jintao SHI, Shuangwei LU, Meng YU. Propofol Modulates the miR-142-3p/RAC1/NF-κB Axis to Influence Knee Osteoarthritis in Rats[J]. Journal of Kunming Medical University.

Propofol Modulates the miR-142-3p/RAC1/NF-κB Axis to Influence Knee Osteoarthritis in Rats

  • Received Date: 2025-09-19
    Available Online: 2026-01-04
  •   Objective  To explore the effect of propofol on pain relief in rats with knee osteoarthritis (KOA) and its regulatory mechanism on the microRNA-142-3p (miR-142-3p)/Ras-related C3 botulinum toxin substrate 1 (RAC1)/nuclear factor-κB (NF-κB) axis.   Methods  A rat knee osteoarthritis model was established by surgically transecting the anterior cruciate ligament, medial collateral ligament, and medial meniscus, with intervention by miR-142-3p antagomir or propofol. Following the conclusion of the intervention, the mechanical pain withdrawal threshold in rats was assessed. Enzyme-linked immunosorbent assay (ELISA) was employed to detect levels of substance P (SP), calcitonin gene-related peptide (CGRP), tumour necrosis factor-α (TNF-α), interleukin (IL)-1β, IL-4 and IL-10 levels in rat serum. Modified Lequesne MG score for assessing knee joint function. Immunofluorescence detection of ionized calcium-binding adaptor molecule 1 (IBA-1) , an activational marker of microglia, in spinal cord tissue. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was employed to determine the relative expression levels of inducible nitric oxide synthase (iNOS), arginase 1 (Arg-1), and miR-142-3p in spinal cord tissue. Western blot analysis of RAC1, p-NF-κB p65 and NF-κB p65 protein expression levels in spinal cord tissue.   Results   Compared with the KOA group, rats in the miR-142-3p antagomir group exhibited a reduced mechanical pain threshold (P < 0.05), increased Lequesne MG scores and serum levels of SP, CGRP, TNF-α, and IL-1β (P < 0.05), serum IL-4 and IL-10 levels, and spinal cord tissue Arg-1 and miR-142-3p expression levels decreased (P < 0.05). Spinal cord tissue IBA-1 fluorescence intensity, iNOS mRNA expression levels, and RAC1 and p-NF-κB p65 protein expression levels increased (P < 0.05). The propofol group exhibited increased mechanical pain thresholds in rats (P < 0.05), reduced Lequesne MG scores and serum levels of SP, CGRP, TNF-α, and IL-1β (P < 0.05), serum IL-4 and IL-10 levels, and spinal cord tissue Arg-1 and miR-142-3p expression levels increased (P < 0.05). Spinal cord tissue IBA-1 fluorescence intensity, iNOS mRNA expression levels, and RAC1 and p-NF-κB p65 protein expression levels decreased (P < 0.05). Compared with the miR-142-3p antagomir group, the propofol group and the propofol+miR-142-3p antagomir group demonstrated significant improvement in the aforementioned indicators in rats (P < 0.05). The miR-142-3p antagomir partially reversed the ameliorative effects of propofol in KOA rats (P < 0.05).   Conclusion   Propofol may inhibit the M1 polarization of microglia, promote the M2 polarization, exert anti-inflammatory effect and inhibit the pain response of KOA rats by regulating the miR-142-3p/RAC1/NF-κB axis.
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