膝宁方治疗肾阳虚膝关节骨性关节炎临床与机理研究
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摘要
膝关节骨性关节炎显著的影响国内大量的人群并导致关节软骨的丢失和严重疼痛与关节废用。在治疗已破坏的关节软骨方面无有效的恢复性药物，而且导致发病的可能性病因学是如此的不同，如何通过中医学的研究在这一领域能起到恢复作用是本次研究的主导思想。
本研究根据中医学关于肾阳虚证的发病学说、临床表现以及涉及到现代医学的生理病理变化情况，探索运用复合因素造模法制造出肾阳虚证膝关节骨性关节炎兔模型。通过对兔血浆、血清的第二信使、激素水平、细胞因子、病理样本超微结构等多项的观察研究，以获得模型的中医证候及部分生物学特点；并在此基础上，比较膝宁方、金匮肾气丸对兔肾阳虚模型的作用表现，探讨异方同证条件下的生物学效应与病证模型之间的关联性，为能进一步研究中医学理论提供实证依据。
论文分为文献综述、临床研究、实验研究三部分。文献综述部分主要从中医关于膝关节骨性关节炎的理论认识历史沿革、膝宁方的立论依据、现代肾阳虚证模型、膝关节骨性关节炎模型进展等方面作一一论述，以揭示课题研究的动因，探讨本研究的理论来源与实践操作的可行性。临床研究部分，通过42例确诊为膝关节骨性关节炎肾阳虚证的入选病例，随机分组后以膝宁方与节宗(美洛西康)治疗。在患者自评疼痛积分、临床症状和体征评分、中医证候积分评分等多项评分指标下，以综合评定两组间处理后的疗效。发现两组疗效接近，膝宁方组具有改善膝关节骨性关节炎的疼痛积分和功能的作用。在部分中医证候学指标上优于节宗组，在药物副反应发生率指标上低于节宗组。实验研究主要从膝宁方的基础研究着手，从膝宁方急性毒性试验、神经-内分泌-免疫功能的变化、抗炎镇痛、微循环变化的调节作用等诸方面进行了探讨。兔膝关节骨性关节炎肾阳虚证模型表现出具有类似肾阳虚的症状，存在提示阳虚证的分子学行为改变，也表现出具有骨性关节炎的细胞因子、炎症指标的变化。提示模型制作成功，膝宁方可以使模型诸多分子学、形态学指标改善。
结论：通过本研究对膝关节骨性关节炎中医肾阳虚证动物模型的制作与膝宁方对模型的作用以及临床治疗学方面的研究，提示本研究对揭示中医药的作用机制，生物学基础，进一步提高临床对膝骨关节炎的防治水平，提高膝骨关节炎患者的生活质量，减轻病废率具有积极意义，并能为进一步研究中医药提供良好的思路。
Osteoarthritis affects a significant proportion of the Chinese population and theresulting loss of articular cartilage and severe pain and disability. There are no effectivetreatments for repair of the damaged articular cartilage in these diseases and while theirlikely aetiologies are very different. How to partially repair the articular cartilage is theleading thought of the study by TCM.
The dissertation was to explore the rabbit knee joint osteoarthritis (KOA) model ofKidney-YANG deficiency which was made by the method of compound causes of diseaseaccording to the TCM's theories of attack, clinical manifestation and physiological andpathological characteristics of modern diseases about this syndrome, and to acquire theChinese medicine syndrome and some biological characteristics of this model throughobserving many targets about the second messenger, hormone level, cytokine, pathologicalcharacteristics bone samples ultramicrostructure and so on, which was indwelled in therabbit's blood plasma and serous. On these achievements, the actions from the XININGFormula and JingKuiShenQi Bill which were administrationed into the KOA rabbit'smodels were abserved and compared to investigate the biological effects and the relevancebetween the models of disease and syndromes on the condition of different prescription onthe same syndrome. On these grounds, the dissertation was to provide substantial basis forfurther revealing and exploring the theories of TCM.
The dissertation contained of documental summarization, clinical research andlaboratory study. The documental summarization contained of successive changes fromSpring & Autumn and Warring States Periods to Qing Dynasty of the theories of TCMabout KOA, the basis of argumentation about XINING Formula, modem models aboutsyndrome of deficiency of Kidney-YANG. We can reveal the causes of the question forstudy and investigate the origin of the theory about the study as well as the feasibility of theoperation about the KOA models. 42 patients' samples with KOA of Kidney-YANGdeficiency were selected and randomized into the group of XINING Formula and the group of Meloxicam for clinical research. To evaluate the therapeutic effects of the two sets afteradministration on the basis of the scores of pain evaluated by patients privately, the scoresof clinical signs and symptoms, the scores of symptoms of TCM, and so on. The therapeuticeffects were similar between the group of XINING Formula and Meloxicam, the group ofXINING Formula improved the KOA patients' scores of pain and ameliorated the knee jointfunction. The XINING Formula had an advantage over Meloxicam about partial indexes ofsyndromes of TCM. The XINING Formula's medicine adverse reactions were lower thanMeloxicam's afer therapy. Laboratory study initiated primarily from the acute toxicity testto nerve-endocrine-immunity system, anti-inflammatory and relieve pain test,microcirculation test. On these achievements, the KOA rabbit's models manifested theresembled systems of Kidney-YANG deficiency which hinted to the molecule'smanifestations according to modern TCM theories and laboratory study as well ascytokines, inflammantory idexes of osteoarthritis. All of these molecule changesdemonstrated the models were made successfully. XINING Formula can ameliorate manyindexes of the immunology and osteoarthritis's cytokines, inflammatory by theKidney-YANG deficiency KOA rabbit models experimental study.
Conclusions: Kidney-YANF deficiency KOA rabbit models were made successfully.Experimental study demonstrated XINING Formula could ameliorate laboratory indexes ofthe rabbit models. Clinical research demonstrated XINING Formula could ameliorate theKOA patients symptoms and signs. All of these demonstrations revealed the TCM'smechanism of action and TCM symptoms' basis of biology laboratory. We discuss theprobable mechanism of therapeutic effect of XINING Formula on OA, so as to get a deepunderstand in the rationale of using XINING Formula as a choice in the prevention andtreatment work of osteoarthritis in clinical work, to enhance the KOA patients quality oflife, to decrease the KOA patients disable ratio, to provide favourable approaches to studyTCM.
本研究根据中医学关于肾阳虚证的发病学说、临床表现以及涉及到现代医学的生理病理变化情况，探索运用复合因素造模法制造出肾阳虚证膝关节骨性关节炎兔模型。通过对兔血浆、血清的第二信使、激素水平、细胞因子、病理样本超微结构等多项的观察研究，以获得模型的中医证候及部分生物学特点；并在此基础上，比较膝宁方、金匮肾气丸对兔肾阳虚模型的作用表现，探讨异方同证条件下的生物学效应与病证模型之间的关联性，为能进一步研究中医学理论提供实证依据。
论文分为文献综述、临床研究、实验研究三部分。文献综述部分主要从中医关于膝关节骨性关节炎的理论认识历史沿革、膝宁方的立论依据、现代肾阳虚证模型、膝关节骨性关节炎模型进展等方面作一一论述，以揭示课题研究的动因，探讨本研究的理论来源与实践操作的可行性。临床研究部分，通过42例确诊为膝关节骨性关节炎肾阳虚证的入选病例，随机分组后以膝宁方与节宗(美洛西康)治疗。在患者自评疼痛积分、临床症状和体征评分、中医证候积分评分等多项评分指标下，以综合评定两组间处理后的疗效。发现两组疗效接近，膝宁方组具有改善膝关节骨性关节炎的疼痛积分和功能的作用。在部分中医证候学指标上优于节宗组，在药物副反应发生率指标上低于节宗组。实验研究主要从膝宁方的基础研究着手，从膝宁方急性毒性试验、神经-内分泌-免疫功能的变化、抗炎镇痛、微循环变化的调节作用等诸方面进行了探讨。兔膝关节骨性关节炎肾阳虚证模型表现出具有类似肾阳虚的症状，存在提示阳虚证的分子学行为改变，也表现出具有骨性关节炎的细胞因子、炎症指标的变化。提示模型制作成功，膝宁方可以使模型诸多分子学、形态学指标改善。
结论：通过本研究对膝关节骨性关节炎中医肾阳虚证动物模型的制作与膝宁方对模型的作用以及临床治疗学方面的研究，提示本研究对揭示中医药的作用机制，生物学基础，进一步提高临床对膝骨关节炎的防治水平，提高膝骨关节炎患者的生活质量，减轻病废率具有积极意义，并能为进一步研究中医药提供良好的思路。
Osteoarthritis affects a significant proportion of the Chinese population and theresulting loss of articular cartilage and severe pain and disability. There are no effectivetreatments for repair of the damaged articular cartilage in these diseases and while theirlikely aetiologies are very different. How to partially repair the articular cartilage is theleading thought of the study by TCM.
The dissertation was to explore the rabbit knee joint osteoarthritis (KOA) model ofKidney-YANG deficiency which was made by the method of compound causes of diseaseaccording to the TCM's theories of attack, clinical manifestation and physiological andpathological characteristics of modern diseases about this syndrome, and to acquire theChinese medicine syndrome and some biological characteristics of this model throughobserving many targets about the second messenger, hormone level, cytokine, pathologicalcharacteristics bone samples ultramicrostructure and so on, which was indwelled in therabbit's blood plasma and serous. On these achievements, the actions from the XININGFormula and JingKuiShenQi Bill which were administrationed into the KOA rabbit'smodels were abserved and compared to investigate the biological effects and the relevancebetween the models of disease and syndromes on the condition of different prescription onthe same syndrome. On these grounds, the dissertation was to provide substantial basis forfurther revealing and exploring the theories of TCM.
The dissertation contained of documental summarization, clinical research andlaboratory study. The documental summarization contained of successive changes fromSpring & Autumn and Warring States Periods to Qing Dynasty of the theories of TCMabout KOA, the basis of argumentation about XINING Formula, modem models aboutsyndrome of deficiency of Kidney-YANG. We can reveal the causes of the question forstudy and investigate the origin of the theory about the study as well as the feasibility of theoperation about the KOA models. 42 patients' samples with KOA of Kidney-YANGdeficiency were selected and randomized into the group of XINING Formula and the group of Meloxicam for clinical research. To evaluate the therapeutic effects of the two sets afteradministration on the basis of the scores of pain evaluated by patients privately, the scoresof clinical signs and symptoms, the scores of symptoms of TCM, and so on. The therapeuticeffects were similar between the group of XINING Formula and Meloxicam, the group ofXINING Formula improved the KOA patients' scores of pain and ameliorated the knee jointfunction. The XINING Formula had an advantage over Meloxicam about partial indexes ofsyndromes of TCM. The XINING Formula's medicine adverse reactions were lower thanMeloxicam's afer therapy. Laboratory study initiated primarily from the acute toxicity testto nerve-endocrine-immunity system, anti-inflammatory and relieve pain test,microcirculation test. On these achievements, the KOA rabbit's models manifested theresembled systems of Kidney-YANG deficiency which hinted to the molecule'smanifestations according to modern TCM theories and laboratory study as well ascytokines, inflammantory idexes of osteoarthritis. All of these molecule changesdemonstrated the models were made successfully. XINING Formula can ameliorate manyindexes of the immunology and osteoarthritis's cytokines, inflammatory by theKidney-YANG deficiency KOA rabbit models experimental study.
Conclusions: Kidney-YANF deficiency KOA rabbit models were made successfully.Experimental study demonstrated XINING Formula could ameliorate laboratory indexes ofthe rabbit models. Clinical research demonstrated XINING Formula could ameliorate theKOA patients symptoms and signs. All of these demonstrations revealed the TCM'smechanism of action and TCM symptoms' basis of biology laboratory. We discuss theprobable mechanism of therapeutic effect of XINING Formula on OA, so as to get a deepunderstand in the rationale of using XINING Formula as a choice in the prevention andtreatment work of osteoarthritis in clinical work, to enhance the KOA patients quality oflife, to decrease the KOA patients disable ratio, to provide favourable approaches to studyTCM.
引文
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