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海桐皮方凝胶贴膏对大鼠膝骨关节炎作用机制OA

Mechanism of action of holly bark gel patch on rats with knee osteoarthritis

中文摘要英文摘要

目的:探讨海桐皮方凝胶贴膏对膝骨关节炎(KOA)大鼠的治疗效果及调控 SOCS3/JAK/STAT 信号通路的分子机制.方法:36 只 8 周龄 SPF 级 SD 大鼠随机分为空白组、假手术组、骨关节炎对照组和治疗组.采用Panicker 法构建 KOA 大鼠模型,治疗组给予海桐皮方凝胶贴膏外用,骨关节炎对照组给予空白贴膏,连续干预 2 个疗程.通过行为学检测评估大鼠机械压痛阈值(PWT)、热辐射痛阈值(PWL)及膝关节直径(KD).ELISA 检测血清 IL-1β、IL-6、TNF-α水平;HE 和番红 O-固绿染色观察软骨形态;RT-qPCR 和 Western blot 检测软骨组织中SOCS3、COX-2、JAK2、STAT3 基因及相关蛋白表达水平.结果:行为学结果显示,海桐皮方凝胶贴膏干预 2 周后,治疗组大鼠 PWL 恢复,与空白组比较,差异无统计学意义(P>0.05).PWT 呈持续上升趋势,膝关节肿胀程度较骨关节炎对照组恢复更快.ELISA 表明,较骨关节炎对照组,治疗组血清 IL-1β、IL-6、TNF-α水平下调(P<0.01).组织学染色显示,海桐皮方凝胶贴膏干预后软骨表面趋于光滑,结构完整性改善,软骨细胞排列规整,番红 O 染色恢复明显,蛋白多糖丢失减少.分子生物学检测显示,治疗组 SOCS3 基因及蛋白表达较骨关节炎对照组升高,COX-2 表达显著降低,p-JAK2/JAK2、p-STAT3/STAT3 比值下降(P<0.01).结论:海桐皮方凝胶贴膏可缓解KOA 大鼠的疼痛与关节肿胀,保护关节软骨,其机制可能与上调 SOCS3 表达,增强对 JAK/STAT 信号通路的负向调控,抑制下游促炎因子释放有关.

Objective:To explore therapeutic effect of the Haidongpi formula gel plaster on knee osteoarthritis(KOA)in rats and the molecular mechanism of regulating the SOCS3/JAK/STAT signaling pathway.Methods:36 8-week-old SPF-grade SD rats were randomly divided into blank group,sham operation group,KOA control group,and treatment group.KOA rat model was established by the Panicker method.The treatment group was treated with Haidongpi formula gel plaster externally,while the KOA control group was treated with blank plasters.The inter-vention lasted for two courses.The mechanical pain threshold(PWT),thermal radiation pain threshold(PWL),and knee joint diameter(KD)of the rats were evaluated by behavioral tests.The levels of IL-1β,IL-6,and TNF-αin ser-um were detected by ELISA.The morphology of cartilage was observed by HE and safranin O-fast green staining.The expression levels of SOCS3,COX-2,JAK2,and STAT3 genes and related proteins in cartilage tissue were detec-ted by RT-qPCR and Western blot.Results:Behavioral tests showed that after 2 weeks of intervention with the Haid-ongpi formula gel plaster,PWL of the treatment group rats recovered,and there was no statistically significant differ-ence compared with the blank group(P>0.05).The PWT showed continuous upward trend,and the degree of knee joint swelling recovered faster than that of the KOA control group.ELISA indicated that the levels of IL-1β,IL-6,and TNF-αin the serum of the treatment group were lower than those in the KOA control group(P<0.01).Histological staining showed that after intervention with the Haidongpi formula gel plaster,surface of the cartilage became smoot-her,structural integrity improved,arrangement of chondrocytes became regular,and safranin O staining recovered significantly,with less loss of proteoglycans.Molecular biological detection showed that the expression of SOCS3 gene and protein in the treatment group was higher than that in the KOA control group,the expression of COX-2 was significantly decreased,and the ratios of p-JAK2/JAK2 and p-STAT3/STAT3 decreased(P<0.01).Conclusion:Haidongpi formula gel plaster can relieve pain and joint swelling in KOA rats and protect joint cartilage.The mecha-nism may be related to the upregulation of SOCS3 expression,enhancing the negative regulation of the JAK/STAT signaling pathway,and inhibiting the release of downstream pro-inflammatory factors.

夏迪;张清;李法杰;侯晓宙;杨满红;万田豪;谷金玉

中国中医科学院西苑医院,北京 100091中国中医科学院望京医院,北京 100102中国中医科学院望京医院,北京 100102中国中医科学院望京医院,北京 100102中国中医科学院望京医院,北京 100102中国中医科学院望京医院,北京 100102中国中医科学院西苑医院,北京 100091

医药卫生

海桐皮方凝胶贴膏膝骨关节炎细胞因子信号转导抑制因子 3Janus 激酶/信号转导和转录激活蛋白

Haitongpi formula gel patchKnee osteoarthritisSOCS3JAK/STAT

《陕西中医》 2026 (5)

579-584,6

国家自然科学基金青年基金资助项目(82505627)北京市自然科学基金资助项目(7244503)首都卫生发展科研专项项目(首发2024-1-7161)

10.3969/j.issn.1000-7369.2026.05.001

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