目的 探讨吡非尼酮对坐骨神经损伤大鼠神经再生的作用。方法 大鼠划分为四组:生理盐水组(Ctrl组),25 mg/kg吡非尼酮组(LG组),50 mg/kg吡非尼酮组(MG组),100 mg/kg吡非尼酮组(HG组)。建立大鼠自体移植修复模型。通过透射电镜(TEM)评估再生神经的形态。Masson染色、坐骨神经功能指数(SFI)评估运动功能的恢复。通过免疫组化测定再生神经中的转化生长因子-β1(TGF-β1)水平。结果 TEM结果提示,术后12周MG 组和 HG 组的有髓神经纤维直径及平均髓鞘厚度均高于Ctrl组和LG组,G值均低于Ctrl组和LG组;术后8周及12周,MG 组和HG组的腓肠肌纤维百分比及SFI均高于Ctrl组和LG组,差异均有统计学意义(P＜0.05)。免疫组化结果提示,与Ctrl 组和 LG 组相比,MG 组和 HG 组的 TGF-β1表达明显下调,差异有统计学意义(P＜0.05)。结论 吡非尼酮促进周围神经损伤大鼠神经再生并改善肌肉功能,可能与吡非尼酮的抗纤维化特性有关。
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.
关键词
吡非尼酮 /
周围神经损伤 /
神经瘢痕 /
神经再生
Key words
pirfenidone /
peripheral nerve injury /
nerve scarring /
nerve regeneration
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基金
福建省自然科学基金(2021J011273, 2022J01492);联勤保障部队第900医院战创伤救治课题(2023ZS07)
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