| 引用本文: |
吴昊, 龚志贤, 卢敏, 邝高艳, 许晓彤, 唐志明.黄栀理伤贴膏对兔膝骨关节炎滑膜组织TLR4/MyD88信号通路的影响[J].湖南中医药大学学报,2025,45(7):1195-1202[点击复制] |
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| 黄栀理伤贴膏对兔膝骨关节炎滑膜组织TLR4/MyD88信号通路的影响 |
| 吴昊,龚志贤,卢敏,邝高艳,许晓彤,唐志明 |
| (湖南中医药大学第一中医临床学院, 湖南 长沙 410007;湖南中医药大学第一附属医院, 湖南 长沙 410007) |
| 摘要: |
| 目的 探讨黄栀理伤贴膏对兔膝骨关节炎（KOA）、滑膜组织Toll样受体4（TLR4）/髓细胞分化初级反应蛋白88（MyD88）信号通路的影响。方法 将新西兰兔随机分为空白组（6只）、KOA造模组（18只）。采用膝关节腔注射木瓜蛋白酶与L-半胱氨酸混合液对KOA造模组进行造模，将KOA造模组中15只造模成功的新西兰兔分为模型组、骨通贴膏组、黄栀理伤贴膏组，每组5只。模型组予胶布贴敷，骨通贴膏组予骨通贴膏贴敷，黄栀理伤贴膏组予黄栀理伤贴膏贴敷，干预每次8 h，1次/d，连续4周。空白组不予处理。观察各组新西兰兔一般情况、X线摄像、关节软骨大体观；采用Pelletier评分评估软骨损伤情况；ELISA检测血清、滑膜组织肿瘤坏死因子-α（TNF-α）含量；Western blot和RT-qPCR检测滑膜组织TLR4、MyD88蛋白及mRNA表达水平。结果 X线摄像显示膝关节不同程度退行性改变，模型组、骨通贴膏组、黄栀理伤贴膏组退行性改变较空白组显著，但骨通贴膏组、黄栀理伤贴膏组较模型组轻。软骨大体观显示模型组右后膝关节退变与软骨损伤较空白组明显，骨通贴膏组、黄栀理伤贴膏组关节退变及软骨损伤较模型组改善。与空白组比较，模型组Pelletier评分、血清和滑膜组织TNF-α含量、滑膜组织中TLR4和MyD88的蛋白及mRNA表达水平均升高（P<0.001）；与模型组比较，骨通贴膏组及黄栀理伤贴膏组Pelletier评分、血清和滑膜组织TNF-α含量、滑膜组织中TLR4和MyD88的蛋白及mRNA表达水平降低（P<0.05，P<0.001）。与骨通贴膏组比较，黄栀理伤贴膏组血清和滑膜组织TNF-α表达水平、滑膜组织中TLR4和MyD88的蛋白及mRNA表达水平降低（P<0.05，P<0.01，P<0.001）。结论 黄栀理伤贴膏能有效延缓兔KOA疾病进展，其作用机制可能与抑制滑膜组织TLR4/MyD88信号通路的活化，从而减轻炎症反应相关。 |
| 关键词: 黄栀理伤贴膏 膝骨关节炎 滑膜组织 Toll样受体4 髓细胞分化初级反应蛋白88 炎症指标 |
| DOI：10.3969/j.issn.1674-070X.2025.07.001 |
| 投稿时间：2025-03-17 |
| 基金项目:国家自然科学基金面上项目（82274543）；湖南省中医药管理局项目（C2023014）；长沙市自然科学基金项目（kq2208209）。 |
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| Effects of Huangzhi Lishang Plaster on the TLR4/MyD88 signaling pathway in synovial tissue of rabbits with knee osteoarthritis |
| WU Hao, GONG Zhixian, LU Min, KUANG Gaoyan, XU Xiaotong, TANG Zhiming |
| (The First Clinical School of Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan 410007, China;The First Hospital of Hunan University of Chinese Medicine, Changsha, Hunan 410007, China) |
| Abstract: |
| Objective To investigate the effects of Huangzhi Lishang Plaster (HZLSP) on the Toll-like receptor 4 (TLR4)/myeloid differentiation primary response protein 88 (MyD88) signaling pathway in the synovial tissue of rabbits with knee osteoarthritis (KOA). Methods New Zealand rabbits were randomly divided into a blank group (n=6) and a KOA model group (n=18). KOA in the model group was induced via intra-articular injection of a mixed solution of papain and L-cysteine into the knee joint. Fifteen successfully modeled rabbits from the KOA model group were further divided into a model group, a Gutong Plaster (GTP) group, and a HZLSP group, with 5 rabbits in each group. The model, GTP, and HZLSP groups received adhesive tape, GTP, and HZLSP applications respectively. The intervention was administered once daily for 8 hours per session, for 4 consecutive weeks. The blank group received no treatment. General conditions, X-ray imaging, and gross morphology of articular cartilage were observed in each group. Cartilage damage was evaluated using the Pelletier scoring system. ELISA was used to measure the expression levels of tumor necrosis factor-α (TNF-α) in serum and synovial tissue. Western blot and RT-qPCR were used to check the protein and mRNA expression levels of TLR4 and MyD88 in synovial tissue. Results X-ray imaging showed varying degrees of degenerative changes in the knee joints. Animals in the model group, GTP group, and HZLSP group exhibited more pronounced degenerative changes compared to the blank group; however, the degenerative changes in animals of the GTP and HZLSP groups were less severe than those in the model group. Gross morphology of cartilage showed that the model group had more apparent degeneration and cartilage damage in the right posterior knee joint compared to the blank group, while joint degeneration and cartilage damage were ameliorated in the GTP and HZLSP groups relative to the model group. Compared with the blank group, the model group had significantly increased Pelletier scores, TNF-α expression levels in serum and synovial tissue, and protein and mRNA expression levels of TLR4 and MyD88 in synovial tissue (P<0.001). Compared with the model group, animals in the GTP and HZLSP groups had reduced Pelletier scores, TNF-α expression levels in serum and synovial tissue, and protein and mRNA expression levels of TLR4 and MyD88 in synovial tissue (P<0.05, P<0.001). Compared with the GTP group, the HZLSP group showed further reductions in TNF-α expression levels in serum and synovial tissue, and in protein and mRNA expression levels of TLR4 and MyD88 in synovial tissue (P<0.05, P<0.01, P<0.001). Conclusion HZLSP can effectively delay the progression of KOA in rabbits, and its mechanism of action may be related to the inhibition of TLR4/MyD88 signaling pathway activation in synovial tissue, thereby alleviating inflammation. |
| Key words: Huangzhi Lishang Plaster knee osteoarthritis synovial tissue Toll-like receptor 4 myeloid differentiation primary response protein 88 inflammatory marker |
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