Abstract: BACKGROUND: Studies have shown that insulin-like growth factor 1/platelet-derived growth factor has an inhibitory effect on fibroblast apoptosis. miR-141-3p in bone marrow stromal cells increases with age and has a relationship with the activation of inflammatory signaling pathways, suggesting that it may be a therapeutic target for lumbar disc herniation.
OBJECTIVE: To explore the effects of miR-141-3p on dorsal root ganglion inflammation and lower limb pain in rats with lumbar disc herniation by regulating insulin-like growth factor 1/platelet-derived growth factor. 
METHODS: Fifty male Sprague-Dawley rats, SPF level, were randomly divided into normal group, model group, miR-NC group, miR-141-3p inhibitor group and miR-141-3p mimics group, with 10 rats in each group. Except for the normal group, animal models of lumbar disc herniation were established in rats by autologous nucleus pulposus transplantation. After successful modeling, rats in the miR-NC, miR-141-3p inhibitor and miR-141-3p mimics groups were injected intrathecally with 10 μL of 20 μmol/L miR-NC, miR-141-3p inhibitor, miR-141-3p mimics, once a day for 28 days, respectively, while those in the normal and model groups were injected with the same volume of saline at the same location at the same time. Paw withdrawal thermal latency threshold was used to evaluate lower limb pain in rats. The mRNA expression of miR-141-3p in dorsal root ganglion tissue was detected by real-time fluorescence quantitative PCR, the levels of inflammatory factors in dorsal root ganglion tissue were detected by ELISA, and the expression of insulin-like growth factor 1/platelet-derived growth factor in dorsal root ganglion tissue was detected by western blot. The correlation between miR-141-3p and insulin-like growth factor 1/platelet-derived growth factor was analyzed.
RESULTS AND CONCLUSION: There were no significant differences in all indexes between the miR-NC group and the model group. Paw withdrawal thermal latency threshold was significantly lower in the model group than in the normal group (P < 0.05), significantly lower in the miR-141-3p inhibitor group than the miR-NC group (P < 0.05), and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The mRNA expression of miR-141-3p in dorsal root ganglion tissue was significantly lower in the model group than in the normal group (P < 0.05), significantly lower in the miR-141-3p inhibitor group than in the miR-NC group (P < 0.05), and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The levels of tumor necrosis factor α, interleukin 1β, and interleukin 1 in dorsal root ganglion tissue were significantly higher in the model group than in the normal group (P < 0.05), significantly higher in the miR-141-3p inhibitor group than in the miR-NC group (P < 0.05), and significantly lower in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The protein expressions of insulin-like growth factor 1 and platelet-derived growth factor in dorsal root ganglion tissue were significantly lower in the model group than in the normal group (P < 0.05), significantly lower in the miR-141-3p inhibitor group than in the miR-NC group (P < 0.05), and significantly higher in the miR-141-3p mimics group than in the miR-141-3p inhibitor group (P < 0.05). The expressions of insulin-like growth factor 1 and platelet-derived growth factor showed a positive correlation with miR-141-3p (r=0.904, P < 0.001; r=0.879, P < 0.001). To conclude, miR-141-3p can significantly improve lower limb pain and inhibit inflammation in dorsal root ganglia in rats with lumbar disc herniation, and its mechanism may be related to the promotion of insulin-like growth factor 1/platelet-derived growth factor expression.

Key words: miR-141-3p, IGF-1/PDGF, lumbar disc herniation, dorsal root ganglion inflammation, lower extremity pain