Effects of pirfenidone on nerve regeneration and functional recovery after sciatic nerve injury in rats
QI Jingtian1, ZHANG Yongguang1, XU Yongjun2, SHENG Qingsong3, CAI Longyu1, YE Yongping1
1. Department of Orthopaedics of the 900th Hospital of PLA Joint Logistics Support force; 2. Fujian Provincial Key Laboratory of Transplantation Biology of Fuzong Clinical Medicine College of Fujian Medical University; 3. Department of Obstetrics and Gynecology of Dongfang Hospital Affiliated to Xiamen University, Fuzhou 350025, China
Abstract：Objective To investigate the effect of pirfenidone on nerve regeneration in rats with sciatic nerve injury. Methods Rats with sciatic nerve injury were divided into four groups: normal saline group (control group, Ctrl), 25 mg/kg pirfenidone group (low-dose group, LG), 50 mg/kg pirfenidone group (medium-dose group, MG), and 100 mg/kg pirfenidone group (high-dose group, HG). An autograft repair model was established. The morphology of regenerative nerves was evaluated by electron microscopy (TEM). The recovery of motor function was assessed by Masson staining and sciatic functional index (SFI). The levels of transforming growth factor-β1 (TGF-β1) in regenerative nerves were determined by immunohistochemical staining. Results TEM results showed that the diameter of myelinated nerve fibers and the mean thickness of myelin sheath in the MG and HG groups were higher than those in the Ctrl and LG groups, and the G ratio were lower than those in the Ctrl and LG groups at 12 weeks after surgery. At both 8 and 12 weeks after surgery, the value of the percentage of gastrocnemius fibers and SFI in the MG and HG groups were significantly higher than those in the Ctrl and LG groups, and the differences were statistically significant(P<0.05). Immunohistochemical results indicated that TGF-β1 expression in the MG and HG groups was significantly down-regulated compared with the Ctrl and LG groups, and the difference was statistically significant (P<0.05). Conclusions Pirfenidone can promote nerve regeneration and improve muscular function in rats with peripheral nerve injury, which may be related to its anti-fibrotic properties of pirfenidone.
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