【作者】 刘孟宇；

【导师】 周翠英；

【作者基本信息】 山东中医药大学 ， 中医内科学， 2008， 博士

【摘要】 本研究以祖国医学理论为指导,从理论探讨、临床疗效观察及实验研究三方面对中药骨痹清方治疗膝骨关节炎(KOA)并滑膜炎的机制进行了探索。提出KOA并滑膜炎的主要病机是湿热痰瘀胶结,蕴化为毒,痹阻气血经络,损伤筋骨关节,日久致痹。治以清热解毒利湿为主,兼以活血、扶正,选用根据导师多年临床经验拟定的“骨痹清方”,从宏观临床疗效和微观细胞水平两方面探讨其治疗机理。临床将98例符合KOA并滑膜炎患者随机分为观察组(骨痹清方组)和对照组(新癀片组),以临床总疗效、中医证候、WOMAC问卷以及临床症状体征总体评分和单一症状体征评分等为观察指标,并根据服药不同时程,分阶段评价其临床疗效及安全性。结果显示骨痹清方能明显改善KOA并滑膜炎患者中医证候、生理功能和临床症状体征,疗效优于新癀片组,观察期内疗效与疗程成正相关,且无明显的毒副反应,安全性高。实验研究应用MTT法、流式细胞仪和RT-PCR等方法观测不同浓度的骨痹清方、新癀片药液对体外培养KOA并滑膜炎患者滑膜成纤维细胞(OA-FLS)增殖分化的影响。结果骨痹清方和新癀片均能抑制OA-FLS增殖,两种药物生理剂量下可抑制OA-FLS有丝分裂,缩短S期,延长G1期,高浓度骨痹清方能诱导OA-FLS细胞凋亡;骨痹清方能明显抑制OA-FLS细胞c-fos和COX-2 mRNA表达。结论:以骨痹清方为代表的清热解毒利湿方药能直接从转录水平抑制OA-FLS细胞的增殖分化,通过多途径、多环节、多靶点发挥整体调节作用,逆转湿热郁毒痹阻的根本病机,从而抑制滑膜炎症,减轻软骨破坏,从根本上治疗膝骨关节炎并滑膜炎。更多还原

【Abstract】 In this study,we take the medical theory of Traditional Chinese medicine (TCM) as a guide and investigate the mechanism of Gubiqing-Recipe in knee osteoarthritis (KOA) complicated with gonarthromeningitis from the theoretical study, clinical observations and experimental study.KOA is induced by damp-heat toxin for the Arthralgia Syndrome. Arthralgia Syndrome is caused by damp-heat, phlegm and blood stasis which are coagulated and accumulated into toxin, blockage of qi-blood circulation and damages of bones joints. We advocate using clearing away the heat-evil, expelling superficial evils, removing dampness as the chief treatment, and activating blood circulation to dissipate blood stasis, strengthening the body resistance meanwhile. The patients were treated with Gubiqing-Recipe that on establishment of tutor years of clinical experience of KOA. To explore possible action mechanism of KOA treatment of clinical efficacy from the macro and the cellular level from micro. 98 cases with KOA complicated with gonarthro- meningitis were randomly divided into test group (Gubiqing-Recipe) and control group (Xinhuang Tablet). Two groups take the indicators for observation such as total curative effect, TCM syndrome, WOMAC questionnaire, the clinical symptoms and signs of a single overall score and score symptoms and signs. Clinical efficacy and safety in accordance with time-phased medication was evaluated. The results show that Gubiqing-Recipe can significantly improve the KOA complicated with gonarthro- meningitis patients’TCM systemic symptoms, physiological functions,symptoms and signs. The Gubiqing-Recipe group curative effect surpasses the Xinhuang Tablet group. In observation period curative effect superiority along with treatment time expands. Gubiqing-Recipe has not obvious poisonous side reaction and has highly the security. We raise the OA-FLS cells in vitro of KOA complicated with gonarthromeningitis patients’synovial membrane, and observe the influence of different concentrations Gubiqing-Recipe and Xinhuang Tablet on cell growth and proliferation by MTT, flow cytometry and RT-PCR methods. The results show that Gubiqing-Recipe and Xinhuang Tablet can suppress the OA-FLS multiplication. Two medicines may suppress the OA-FLS mitosis in the physiological dosage, reduces the S time, lengthens the G1 time and the highly concentrated Gubiqing-Recipe can induce the OA-FLS cell apoptosis. Gubiqing-Recipe can obviously inhibited c-fos and COX-2 mRNA expressions of OA-FLS. Conclusion: Gubiqing-Recipe of clearing heat, detoxication, dispelling damp can inhibit OA-FLS cells’proliferation and differentiation directly from the transcription level. Gubiqing-Recipe display conformity control action through multi-ways, multi-links and multi-target. Gubiqing-Recipe can reverse basic pathogenesis that blockage of hot, damp, stasis and poisonous, restrain inflammation of synovium , decrease cartilage destruction, yield a radical cure of KOA complicated with gonarthromeningitis.更多还原