背景:周围神经损伤是临床治疗中具有挑战性的骨科问题,在严重的情况下通常会导致肢体功能障碍甚至残疾。对周围神经损伤的修复过程和潜在机制的深入探索有助于制定更有效的治疗策略。
方法:在本研究中,建立SD大鼠坐骨神经横断损伤模型。然后通过将近端腓总神经与远端胫神经和腓总神经连接的套筒,使用几丁质套管进行小间隙吻合,对坐骨神经横断损伤进行12周的代偿修复,2毫米的间隔。通过神经标本的粗略观察观察到通过小间隙放大的代偿修复,渗透酸染色,并电生理刺激胫骨和腓总神经的坐骨神经分支。观察大鼠四肢,通过称重肌肉湿重评估腓肠肌和胫骨前肌效应肌的功能恢复,苏木精和伊红(H&E)染色,和肌肉力量检测。H&E染色,Masson染色,对甲苯胺蓝染色观察背根神经节的形态学变化。第10号染色体上缺失的磷酸酶和张力蛋白同源物(PTEN)-蛋白激酶B(AKT)/哺乳动物雷帕霉素靶蛋白(mTOR)信号通路的阳性表达,包括PTEN,AKT,mTOR,Toll样受体4(TLR4),坐骨神经损伤后通过小间隙放大代偿修复时,背根神经节中的Caspase9,免疫组织化学染色检测。
结果:发现用几丁质套管代偿性修复坐骨神经横断损伤,通过袖接小间隙吻合,可有效恢复连续性,有髓神经纤维的数量,和神经传导速度.它促进了脚趾外展的恢复,改善肌纤维形态,增加腓肠肌和胫骨前肌的湿重和肌力。此外,它增加了神经元和神经纤维的数量,并改善了它们的形态。下调PTEN,背根神经节TLR4和Caspase9上调AKT和mTOR后较横断损伤组小间隙扩增,更接近对照组。
结论:用几丁质套管经套接小间隙吻合代偿修复坐骨神经横断损伤,可恢复坐骨神经的形态和功能,效应肌,并通过激活背根神经节中的PTEN-AKT/mTOR信号通路来对应背根神经节。我们的发现为周围神经损伤提供了新的治疗靶点。
BACKGROUND: Peripheral nerve injury is a challenging orthopedic issue in clinical management that often leads to limb dysfunction or even disability in severe cases. A thorough exploration of the repair process of peripheral nerve injury and the underlying mechanism contributes to formulate more effective therapeutic strategies.
METHODS: In the present study, we established a sciatic nerve transection injury model in Sprague-Dawley (SD) rats. A 12-week compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis was then performed via sleeve jointing the proximal common peroneal nerve to the distal tibial nerve and common peroneal nerve, with a 2 mm interval. Compensatory repair via small gap amplification was observed via gross observation of nerve specimen, osmic acid staining, and electrophysiological stimulation of sciatic nerve branches of the tibial and common peroneal nerve. Rat limbs were observed, and the functional recovery of effector muscles of the gastrocnemius and tibialis anterior muscles was assessed through weighing the muscle wet weight, Hematoxylin and Eosin (H&E) staining, and muscle strength detection. H&E staining, Masson staining, and toluidine blue staining were performed to observe the morphological changes of the dorsal root ganglion. Positive expressions of key proteins involved in the Phosphatase and tensin homologue deleted on chromosome ten (PTEN)-protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway, including PTEN, AKT, mTOR, Toll-like receptor 4 (TLR4), and Caspase9 in the dorsal root ganglion during compensatory repair of sciatic nerve after injury via small gap amplification, were detected by immunohistochemical staining.
RESULTS: It is found that the compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing effectively restored the continuity, number of myelinated nerve fibers, and nerve conduction velocity. It promoted toe abduction recovery, improved muscle fiber morphology and increased the wet weight and muscle strength of the gastrocnemius muscle and tibialis anterior muscle. Moreover, it increased the number of neurons and nerve fibers, and improved their morphology. Downregulated PTEN, TLR4, and Caspase9 in the dorsal root ganglia and upregulated AKT and mTOR were observed after small gap amplification than those of the transection injury group, which were closer to those of the control group.
CONCLUSIONS: Compensatory repair of sciatic nerve transection injury using a chitin cannula for small gap anastomosis via sleeve jointing can restore the morphology and function of the sciatic nerve, effector muscles, and corresponding dorsal root ganglia by activating the PTEN-AKT/mTOR signaling pathway in the dorsal root ganglia. Our findings provide novel therapeutic targets for peripheral nerve injuries.