理筋整复手法通过TLR4-MyD88-NF-κB信号通路促进膝骨关节炎家兔滑膜炎症的恢复。

Tendon-regulating and bone-setting manipulation promotes the recovery of synovial inflammation in rabbits with knee osteoarthritis via the TLR4-MyD88-NF-κB signaling pathway.

作者信息

Jin Xiangyu, Yu Yangyang, Lin Yongyan, Yang Jinping, Chen Zhaohui

机构信息

College of Acupuncture and Tuina (Rehabilitation Medicine), Anhui University of Chinese Medicine, Hefei, China.

College of Graduate, Anhui University of Chinese Medicine, Hefei, China.

出版信息

Ann Transl Med. 2023 Mar 31;11(6):245. doi: 10.21037/atm-22-3039. Epub 2023 Feb 15.

Abstract

BACKGROUND

The aim of this study was to clarify the mechanism of tendon-regulating and bone-setting manipulation in the treatment of knee osteoarthritis (KOA).

METHODS

A total of 30 adult healthy specific pathogen-free (SPF) New Zealand white rabbits (male; weight 2.0-2.5 kg) were selected and divided into a normal control (NC) group, KOA group, and KOA + manual treatment (MT) group. Each group comprised 10 rabbits. A KOA model was established using the modified Hulth method in the KOA and KOA + MT groups. The 3 groups were fed under the same conditions for 8 weeks. The Lequesne index for KOA was used to evaluate the behavioral status of the model rabbits; hematoxylin and eosin (HE) staining was employed to observe the pathological morphology of the tibial plateau and medial femoral condyle cartilage; the Mankin scoring scale was used to evaluate the cartilage morphology of the model rabbits; Western blot was used to detect the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), and nuclear factor κB (NF-κB) proteins in the synovial tissue of the model rabbits; the contents of interleukin (IL)-1β, IL-6, and, tumor necrosis alpha (TNF-α) in the synovial fluid of the model rabbits were determined using the enzyme-linked immunosorbent assay (ELISA) method.

RESULTS

Compared with those in the NC group, Lequesne index score, Mankin score of cartilage tissue, protein expression, and content of inflammatory factors were significantly increased in the KOA and KOA + MT groups (P<0.05), and these values were significantly higher in the KOA group. Microscopy showed that the cartilage tissue of the experimental rabbits in the KOA and KOA + MT groups was significantly degenerated. Compared with those in the KOA group, the Lequesne index score, Mankin score, protein expression, and inflammatory factor content of the model rabbits in the KOA + MT group were significantly reduced (P<0.05), and microscopy showed that cartilage tissue degeneration of the experimental rabbits in the KOA + MT group was significantly improved.

CONCLUSIONS

Tendon-regulating and bone-setting manipulation can significantly improve the activity state and motor function of KOA model rabbits and significantly inhibit the expression of the TLR4-MyD88-NF-κB signaling pathway in synovial tissue, thereby reducing knee joint synovial inflammation and delaying the occurrence and development of KOA.

摘要

背景

本研究旨在阐明理筋整复手法治疗膝骨关节炎(KOA)的机制。

方法

选取30只成年健康无特定病原体(SPF)新西兰白兔(雄性,体重2.0 - 2.5 kg),分为正常对照组(NC组)、KOA组和KOA + 手法治疗(MT)组,每组10只。采用改良Hulth法在KOA组和KOA + MT组建立KOA模型。3组在相同条件下饲养8周。采用KOA的Lequesne指数评估模型兔的行为状态;采用苏木精-伊红(HE)染色观察胫骨平台和股骨内侧髁软骨的病理形态;采用Mankin评分量表评估模型兔的软骨形态;采用蛋白质免疫印迹法检测模型兔滑膜组织中Toll样受体4(TLR4)、髓样分化因子88(MyD88)和核因子κB(NF-κB)蛋白的表达水平;采用酶联免疫吸附测定(ELISA)法测定模型兔滑液中白细胞介素(IL)-1β、IL-6和肿瘤坏死因子α(TNF-α)的含量。

结果

与NC组相比,KOA组和KOA + MT组的Lequesne指数评分、软骨组织Mankin评分、蛋白表达及炎症因子含量均显著升高(P<0.05),且KOA组上述各项指标更高。显微镜检查显示,KOA组和KOA + MT组实验兔的软骨组织明显退变。与KOA组相比,KOA + MT组模型兔的Lequesne指数评分、Mankin评分、蛋白表达及炎症因子含量均显著降低(P<0.05),显微镜检查显示,KOA + MT组实验兔的软骨组织退变明显改善。

结论

理筋整复手法可显著改善KOA模型兔的活动状态和运动功能,显著抑制滑膜组织中TLR4 - MyD88 - NF - κB信号通路的表达,从而减轻膝关节滑膜炎症,延缓KOA的发生发展。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/251c/10113090/a11e99d41a9b/atm-11-06-245-vid1.jpg

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