| 衣美霞,张蝶,王宁.膝三针调节PPARγ/NF-κB通路对膝骨关节炎大鼠骨代谢及骨微结构的影响[J].中国康复,2026,41(6):323-329 |
| 膝三针调节PPARγ/NF-κB通路对膝骨关节炎大鼠骨代谢及骨微结构的影响 |
| The effects of knee three needles on bone metabolism and microstructure in knee osteoarthritis rats by regulating PPARγ/NF-κB pathway |
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| DOI：10.3870/zgkf.2026.06.001 |
| 中文关键词: 膝三针 过氧化物酶体增殖物激活受体γ 核因子κB 膝骨关节炎 骨代谢 骨微结构 |
| 英文关键词: knee three needles peroxisome proliferator-activated receptor gamma nuclear factor kappa B knee osteoarthritis bone metabolism bone microstructure |
| 基金项目:2023年度军队中医药服务能力培育与提升专项计划（2023ZY025） |
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| 中文摘要: |
| 目的：探讨膝三针调节过氧化物酶体增殖物激活受体γ（PPARγ）/核因子κB（NF-κB）通路对膝骨关节炎（KOA）大鼠骨代谢及骨微结构的影响。方法：关节腔内注射碘乙酸钠溶液构建KOA大鼠，采用随机数字表法将建模成功的大鼠随机分为KOA组、膝三针组（膝三针治疗）、膝三针+GW9662组（膝三针治疗+尾静脉注射1mg/kg GW9662），每组12只，另选择12只为NC组，NC组和KOA组尾静脉注射等量生理盐水，1次/d，每周连续5 d，共治疗3周。检测各组的疼痛行为学［机械痛阈值（PWT）、热痛阈值（PWL）］；酶联免疫吸附测定（ELISA）检测血清中［肿瘤坏死因子-α（TNF-α）、白细胞介素（IL）-1β、IL-6］和骨代谢指标［Ⅰ型胶原C末端肽（CTX-Ⅰ）、骨保护素（OPG）、抗酒石酸酸性磷酸酶（TRACP）、核因子κB受体活化因子配体（RANKL）］的表达；Micro-CT分析大鼠膝关节骨微结构［骨小梁厚度（Tb.Th）、骨小梁数量（Tb.N）、骨小梁结构模式参数（SMI）、骨小梁间距（Tb.Sp）、骨密度（BMD）、骨体积分数（BV/TV）］的改变；苏木精伊红（HE）和甲苯胺蓝染色检测膝关节软骨组织病理变化；蛋白质印迹（Western Blot）检测膝关节软骨组织中PPARγ/NF-κB通路蛋白的表达。结果：NC组软骨组织各层细胞排列整齐、分布均匀；KOA组软骨组织表层不平整，可见细胞减少、排列紊乱、大量空泡；膝三针组软骨组织表层较为平整，细胞数量增多，空泡减少；膝三针+GW9662组软骨组织表层进一步不平整，细胞数量进一步减少，空泡进一步增多。与NC组相比，KOA组PWL、PWT、OPG、Tb.Th、Tb.N、BMD、BV/TV、PPARγ降低，Mankin评分、CTX-Ⅰ、TRACP、RANKL、TNF-α、IL-1β、IL-6、SMI、Tb.Sp、p-NF-κB P65/NF-κB P65升高（P＜0.05）；与KOA组相比，膝三针组PWL、PWT、OPG、Tb.Th、Tb.N、BMD、BV/TV、PPARγ升高，Mankin评分、CTX-Ⅰ、TRACP、RANKL、TNF-α、IL-1β、IL-6、SMI、Tb.Sp、p-NF-κB P65/NF-κB P65降低（P＜0.05）；膝三针+GW9662组可以逆转膝三针组上述因子的变化（P＜0.05）。结论：膝三针通过激活PPARγ进而抑制NF-κB改善KOA大鼠的骨代谢及骨微结构。 |
| 英文摘要: |
| Objective: To explore the effects of knee three needles on bone metabolism and microstructure in knee osteoarthritis (KOA) rats by regulating the peroxisome proliferator-activated receptor gamma (PPARγ)/nuclear factor kappa B (NF-κB) pathway. Methods: Sodium iodoacetate solution was injected into the joint cavity to construct KOA rats. The successfully modeled rats were assigned into KOA group, knee three needles group (knee three needles treatment), and knee three needles+GW9662 group (knee three needles treatment+tail vein injection of 1 mg/kg GW9662), with 12 rats per group. There were 12 animals in the normal control (NC) group. The NC group and KOA group received intravenous injection of an equal amount of physiological saline once a day for 5 consecutive days per week, for a total of 3 weeks of treatment. The pain behavior of each group was tested ［paw withdrawal threshold (PWT), paw withdrawal latency (PWL)］. The enzyme-linked immunosorbent assay (ELISA) was used to detect the expression levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-1β and IL-6, and bone metabolism indicators ［type I collagen C-terminal peptide (CTX-Ⅰ), osteoprotegerin (OPG), tartrate-resistant acid phosphatase (TRACP), and receptor activator of nuclear factor κB ligand (RANKL)］. Micro-CT was used to analyze the changes in the bone microstructure of the rat knee joint ［including trabecular thickness (Tb.Th), trabecular number (Tb.N), structure model index (SMI), trabecular separation (Tb.Sp), bone mineral density (BMD), and bone volume/tissue volume ratio (BV/TV)］. Hematoxylin and eosin (HE) staining and toluidine blue staining were implemented to measure pathological changes in knee cartilage tissue. In addition, Western blot was used to measure the expression of PPARγ/NF-κB pathway proteins in knee cartilage tissue. Results: The cells in each layer of cartilage tissue in the NC group were arranged neatly and distributed evenly. The surface of the cartilage tissue in the KOA group was uneven, with reduced cells, disordered arrangement, and a large number of vacuoles visible. The surface of the cartilage tissue in the knee three needles group was relatively flat, with an increase in the number of cells and a decrease in vacuoles. The surface of the cartilage tissue in the knee three needles+GW9662 group was uneven, with a further decrease in cell number and an increase in vacuoles. Compared with the NC group, the KOA group showed decreases in PWL, PWT, OPG, Tb.Th, Tb.N, BMD, BV/TV, and PPARγ, along with increases in Mankin score, CTX-Ⅰ, TRACP, RANKL, TNF-α, IL-1β, IL-6, SMI, Tb.Sp, and the ratio of p-NF-κB P65 to NF-κB P65 (P<0.05). Compared with the KOA group, the knee three needles group exhibited increases in PWL, PWT, OPG, Tb.Th, Tb.N, BMD, BV/TV, and PPARγ, and decreases in Mankin score, CTX-Ⅰ, TRACP, RANKL, TNF-α, IL-1β, IL-6, SMI, Tb.Sp, and the p-NF-κB P65/NF-κB P65 ratio (P<0.05). The knee three needles+GW9662 group reversed the changes in the above factors induced by the knee three-needle acupuncture intervention (P<0.05). Conclusion: Knee acupuncture improves bone metabolism and microstructure in KOA rats by activating the PPARγ/NF-κB pathway. |
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