Tuina promotes nerve myelin regeneration in SNI rats through Piezo1/YAP/TAZ pathway

The changes in the mechanical environment of local nerves after peripheral nerve injury (PNI) can cause a series of mechanical electrochemical signal reactions that affect the process of nerve regeneration and functional recovery. Piezo1/YAP/TAZ is an important transduction pathway that affects myelin regeneration. Our previous studies showed that Tuina could treat PNI in a variety of ways, including promoting nerve repair. However, whether Tuina as a kind of benign mechanical stimulation could promote nerve repair by changing the neuromechanical environment and causing changes in the mechanical electrochemical signal transduction pathway Piezo1/YAP/TAZ is unknown.

The rats were divided into 4 groups, Sham group, sciatic nerve injury (SNI) group, Tuina group and Tuina + GsMTx4 group, with 6 rats in each group. We established an SNI model. Sciatic nerves at the mid-thigh level were exposed and crushed using a pair of non-serrated forceps for 5 s and the damage points about 2 mm. We used a Tuina manipulation emulator designed by our team to intervent. According to the "Three-Manipulation and Three-Acupoint": the emulator was used to perform the Dian, Bo, and Rou methods on Yinmen (BL37), Chengshan (BL57) and Yanglingquan (GB34) sequentially on the affected side. Each Tuina method was applied for 1 min on each acupoint respectively. Tuina treatment was administered once daily for 20 days. And we observed Somatic Functional Index (SFI), Mechanical Withdrawal Threshold (MWT), electrophysiological test and Shear wave elastography (SWE) examination in each group. Toluidine blue staining was performed to observe nerve fibers. The expression of Piezo1, Yes-associated protein (YAP), transcriptional coactivator with PDZ-binding motif (TAZ), Myelin basic protein (MBP), Neurofilament 200 (NF200), S100 calcium-binding protein β(S100β) and Ca²⁺ were detected using Immunofluorescence (IF), Western Blot (WB), Real-Time Quantitative PCR (RT-PCR) and Calcium Assay Kit.

Tuina improved the SFI, MWT, and compound action potential (CMAP) changes after SNI. The SWE results showed that Tuina reduced Emax and Smax. Piezo1, Ca²⁺ expression were reduced, YAP, TAZ, MBP, NF200, S100β expression were enhanced by Tuina.

The activation of Schwann cells (SCs) and the regeneration of injured nerve myelin post-Tuina intervention are associated with alterations in the Piezo1/YAP/TAZ signaling pathway within SCs, induced by the mechanical forces generated through Tuina.