Wang Zhen, Xu Hui, Wang Zheng, Wang Yu, Diao Jieyao, Chen Juntao, Xie Yuchen, Zhang Lijuan, Li Miaoxiu, Bian Yanqin, Zhou Yunfeng
College of Acupuncture and Massage, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.
Tuina Department, The Third Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.
J Inflamm Res. 2024 Sep 17;17:6501-6519. doi: 10.2147/JIR.S488023. eCollection 2024.
Knee osteoarthritis (KOA) is on the rise due to lifestyle changes, obesity, and aging, yet effective treatments are lacking. Traditional Chinese manual therapy (Tuina) is promising for KOA. However, its mechanism remains unclear.
This study aims to determine the effects of Tuina on a rat KOA model, focusing on the role of chondrocyte apoptosis and autophagy mechanisms.
KOA was induced in rats by intra-articular injection of L-cysteine-activated papain into the right knee. Thirty-six male Sprague Dawley (SD) rats were randomly divided into blank, model control, Tuina, and positive drug groups. Paw withdrawal threshold tests, knee joint swelling, and passive range of motion assessed knee behavior. Cartilage tissue cytology, cytokine contents, and the mRNA and protein expression of PI3K/AKT/mTOR signaling pathway components were analyzed using HE and TUNEL staining, ELISA, RT-qPCR, and Western blotting, respectively. In addition, we used machine learning methods to conduct a secondary analysis of the dataset from the in vivo experiments in rats to verify the findings.
Tuina significantly relieved pain and joint swelling, and improved range of motion. Staining showed reduced articular cartilage destruction and apoptosis. Tuina reduced the serum levels of IL-1β, IL-17, MMP-3, and MMP-13. Tuina downregulated Bax, ULK1, Beclin-1, LC3-II/I and upregulated PI3K, AKT, mTOR, and BCL-2 in cartilage tissue. The machine learning results indicated an 83.33% accuracy for the prediction model, remaining stable through both uni- and multivariate analyses. Tuina yielded the best comprehensive efficacy on KOA as well as better rat behavior and PI3K/AKT/mTOR signaling pathway improvement effect than positive drugs, while its cytokine-reducing ability was comparable to that of positive drugs.
Tuina can alleviate cartilage tissue injury in KOA, relieve inflammation, and reduce chondrocyte apoptosis and autophagy, the underlying mechanisms of which may be associated with activation of the PI3K/AKT/mTOR signaling pathway.
由于生活方式改变、肥胖和老龄化，膝骨关节炎（KOA）的发病率正在上升，但缺乏有效的治疗方法。中医手法治疗（推拿）对KOA有一定前景。然而，其作用机制尚不清楚。
本研究旨在确定推拿对大鼠KOA模型的影响，重点关注软骨细胞凋亡和自噬机制的作用。
通过向大鼠右膝关节腔内注射L-半胱氨酸激活的木瓜蛋白酶诱导KOA。36只雄性Sprague Dawley（SD）大鼠随机分为空白组、模型对照组、推拿组和阳性药物组。通过 paw withdrawal threshold tests、膝关节肿胀和被动活动范围评估膝关节行为。分别使用HE和TUNEL染色、ELISA、RT-qPCR和Western blotting分析软骨组织细胞学、细胞因子含量以及PI3K/AKT/mTOR信号通路成分的mRNA和蛋白表达。此外，我们使用机器学习方法对大鼠体内实验数据集进行二次分析以验证研究结果。
推拿显著减轻疼痛和关节肿胀，改善活动范围。染色显示关节软骨破坏和凋亡减少。推拿降低了血清中IL-1β、IL-17、MMP-3和MMP-13的水平。推拿下调软骨组织中Bax、ULK1、Beclin-1、LC3-II/I的表达，并上调PI3K、AKT、mTOR和BCL-2的表达。机器学习结果表明预测模型的准确率为83.33%，单因素和多因素分析结果均保持稳定。推拿对KOA的综合疗效最佳，对大鼠行为和PI3K/AKT/mTOR信号通路的改善作用优于阳性药物，而其降低细胞因子的能力与阳性药物相当。
推拿可减轻KOA软骨组织损伤，缓解炎症，减少软骨细胞凋亡和自噬，其潜在机制可能与PI3K/AKT/mTOR信号通路的激活有关。
