Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways

ObjectiveTo investigate whether Tuina therapy alleviated inflammation and motor neuron apoptosis in sciatic nerve injury (SNI) rats by regulating cytosolic phospholipase A2 (cPLA2) and Ras homolog family member A/Rho-associated coiled-coil comprising protein kinase 2 (RhoA/ROCK2) signaling cascades....

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Main Authors: Jiawei Sun, Yingqi Zhang, Zhifeng Liu, Hanyu Zhang, Jiayue Liu, Yue Xu, Rentuya Na, Hongzheng Zhang, Jiawang Yan, Tianyuan Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-07-01
Series:Frontiers in Neurology
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Online Access:https://www.frontiersin.org/articles/10.3389/fneur.2025.1622602/full
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author Jiawei Sun
Yingqi Zhang
Zhifeng Liu
Hanyu Zhang
Jiayue Liu
Yue Xu
Rentuya Na
Hongzheng Zhang
Jiawang Yan
Tianyuan Yu
author_facet Jiawei Sun
Yingqi Zhang
Zhifeng Liu
Hanyu Zhang
Jiayue Liu
Yue Xu
Rentuya Na
Hongzheng Zhang
Jiawang Yan
Tianyuan Yu
author_sort Jiawei Sun
collection DOAJ
description ObjectiveTo investigate whether Tuina therapy alleviated inflammation and motor neuron apoptosis in sciatic nerve injury (SNI) rats by regulating cytosolic phospholipase A2 (cPLA2) and Ras homolog family member A/Rho-associated coiled-coil comprising protein kinase 2 (RhoA/ROCK2) signaling cascades.MethodsFour experimental cohorts were established utilizing 36 male Sprague–Dawley rats: control, sham, SNI, and TUI. We implemented a sciatic nerve injury (SNI) model. At dthe mid-thigh level, sciatic nerves were exposed and crushed for 5 s using non-serrated forceps at points spaced approximately 2 mm apart. Postoperatively, Tuina therapy (Chinese therapeutic massage, Tuina) was administered to evaluate its neuromodulatory effects. SNI models were established in the SNI and TUI cohorts. TUI cohorts applied with “Three-Manipulation and Three-Acupoint” technique, which included pressing, plucking, and kneading on the acupoints Yinmen (BL37), Chengshan (BL57), and Yanglingquan (GB34). The control cohort underwent no intervention. The sham surgery and model cohorts underwent restraining interventions. Motor function was assessed using Basso, Beattie, and Bresnahan (BBB) scores and CatWalk gait analysis. Spinal cord (SC) histology was evaluated using hematoxylin and eosin and Nissl staining. NeuN-positive cells were quantified via immunofluorescence. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and aquaporin-4 levels were determined through enzyme-linked immunosorbent assay. RhoA, ROCK2, Bax, Bcl-2, and cPLA2 mRNA levels were analyzed using real-time quantitative polymerase chain reaction. RhoA, ROCK2, Bax, Bcl-2, cPLA2, and p-cPLA2 protein expressions were analyzed using western blotting to investigate the impact of Tuina therapy on nerve regeneration and apoptosis regulation.ResultsThe TUI cohort showed better BBB scores and CatWalk results than the SNI cohort (all p < 0.001). Histological analysis revealed diminished inflammatory cell infiltration and increased neuronal survival. NeuN immunofluorescence indicated decreased motor neuron apoptosis in the anterior horn of the SC. Tuina therapy reversed TNF-α, IL-6, and aquaporin-4 levels (p < 0.01). The TUI cohort had lower mRNA expression of Bax, cPLA2, and ROCK2 (all p < 0.001), mRNA expression of RhoA (p < 0.01), and Bax, cPLA2, p-cPLA2, and RhoA/ROCK2 levels (all p < 0.001) than the SNI cohort. Conversely, mRNA and protein expression levels of Bcl2 were higher in the TUI cohort than in the SNI cohort (all p < 0.001).ConclusionTuina therapy improved motor function in SNI rats by inhibiting motor neuron apoptosis via cPLA2 regulation, potentially via the RhoA/ROCK2 signaling pathway.
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spelling doaj-art-4bf39f10fcc8436bb533cf0167f45daf2025-08-20T03:58:49ZengFrontiers Media S.A.Frontiers in Neurology1664-22952025-07-011610.3389/fneur.2025.16226021622602Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathwaysJiawei Sun0Yingqi Zhang1Zhifeng Liu2Hanyu Zhang3Jiayue Liu4Yue Xu5Rentuya Na6Hongzheng Zhang7Jiawang Yan8Tianyuan Yu9School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaDepartment of Tuina and Pain Management, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaSchool of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, ChinaObjectiveTo investigate whether Tuina therapy alleviated inflammation and motor neuron apoptosis in sciatic nerve injury (SNI) rats by regulating cytosolic phospholipase A2 (cPLA2) and Ras homolog family member A/Rho-associated coiled-coil comprising protein kinase 2 (RhoA/ROCK2) signaling cascades.MethodsFour experimental cohorts were established utilizing 36 male Sprague–Dawley rats: control, sham, SNI, and TUI. We implemented a sciatic nerve injury (SNI) model. At dthe mid-thigh level, sciatic nerves were exposed and crushed for 5 s using non-serrated forceps at points spaced approximately 2 mm apart. Postoperatively, Tuina therapy (Chinese therapeutic massage, Tuina) was administered to evaluate its neuromodulatory effects. SNI models were established in the SNI and TUI cohorts. TUI cohorts applied with “Three-Manipulation and Three-Acupoint” technique, which included pressing, plucking, and kneading on the acupoints Yinmen (BL37), Chengshan (BL57), and Yanglingquan (GB34). The control cohort underwent no intervention. The sham surgery and model cohorts underwent restraining interventions. Motor function was assessed using Basso, Beattie, and Bresnahan (BBB) scores and CatWalk gait analysis. Spinal cord (SC) histology was evaluated using hematoxylin and eosin and Nissl staining. NeuN-positive cells were quantified via immunofluorescence. Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and aquaporin-4 levels were determined through enzyme-linked immunosorbent assay. RhoA, ROCK2, Bax, Bcl-2, and cPLA2 mRNA levels were analyzed using real-time quantitative polymerase chain reaction. RhoA, ROCK2, Bax, Bcl-2, cPLA2, and p-cPLA2 protein expressions were analyzed using western blotting to investigate the impact of Tuina therapy on nerve regeneration and apoptosis regulation.ResultsThe TUI cohort showed better BBB scores and CatWalk results than the SNI cohort (all p < 0.001). Histological analysis revealed diminished inflammatory cell infiltration and increased neuronal survival. NeuN immunofluorescence indicated decreased motor neuron apoptosis in the anterior horn of the SC. Tuina therapy reversed TNF-α, IL-6, and aquaporin-4 levels (p < 0.01). The TUI cohort had lower mRNA expression of Bax, cPLA2, and ROCK2 (all p < 0.001), mRNA expression of RhoA (p < 0.01), and Bax, cPLA2, p-cPLA2, and RhoA/ROCK2 levels (all p < 0.001) than the SNI cohort. Conversely, mRNA and protein expression levels of Bcl2 were higher in the TUI cohort than in the SNI cohort (all p < 0.001).ConclusionTuina therapy improved motor function in SNI rats by inhibiting motor neuron apoptosis via cPLA2 regulation, potentially via the RhoA/ROCK2 signaling pathway.https://www.frontiersin.org/articles/10.3389/fneur.2025.1622602/fullperipheral nerve injuryTuinaapoptosisinflammatory responseCPLA2RhoA/ROCK2 pathway
spellingShingle Jiawei Sun
Yingqi Zhang
Zhifeng Liu
Hanyu Zhang
Jiayue Liu
Yue Xu
Rentuya Na
Hongzheng Zhang
Jiawang Yan
Tianyuan Yu
Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways
Frontiers in Neurology
peripheral nerve injury
Tuina
apoptosis
inflammatory response
CPLA2
RhoA/ROCK2 pathway
title Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways
title_full Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways
title_fullStr Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways
title_full_unstemmed Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways
title_short Chinese massage therapy (Tuina) inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cPLA2 and RhoA/ROCK2 signaling pathways
title_sort chinese massage therapy tuina inhibits motor neuron apoptosis in rats with sciatic nerve injury by regulating the cpla2 and rhoa rock2 signaling pathways
topic peripheral nerve injury
Tuina
apoptosis
inflammatory response
CPLA2
RhoA/ROCK2 pathway
url https://www.frontiersin.org/articles/10.3389/fneur.2025.1622602/full
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