龙鳖胶囊治疗膝关节骨性关节炎的临床研究

【作者】 向孝兵；

【导师】 严大波；

【作者基本信息】 广州中医药大学 ， 中医骨伤科学， 2000， 硕士

【摘要】 膝关节骨性关节炎（OA）是一种严重危害老年人健康的慢性关节疾患，相当于中医“骨痹”范畴。其病理特征为关节软骨出现原发性或继发性退行性变，并伴有软骨下骨质增生。临床上以膝关节疼痛、僵硬及活动受限为主要表现。OA的病因及发病机理尚未完全阐明，目前现代医学对此病除对症治疗或少数情况下做人工关节置换外尚无有效的方法，而用中医方法治疗可取得较好的效果。广东省中医院骨科长期使用的纯中药制剂“龙鳖胶囊”经过多年的临床应用证明，在治疗骨性关节炎方面具有疗效满意、副作用小的特点。本文在总结中西医对OA研究概况的基础上，进行了龙鳖胶囊治疗膝关节OA的临床研究，旨在探讨OA的发病机制和龙鳖胶囊的治疗效果。 第一部分为前言，分为两节。前一节对OA的发病、诊断及治疗情况进行回顾，即OA的概述；后一节论述了前列腺素与骨性关节炎的关系及其调节，指出了前列腺素在骨性关节炎发病过程中的重要作用及浓度变化，将前列腺素作为本临床研究的指标即是以此为理论依据的。 第二部分为文献研究，对近几年来国内外的研究状况加以总结归纳。较为详细地阐述了骨性关节炎的含义与分类，认为本病可分为原发性和继发性两种。原发性OA的发生与年龄、性别、职业工种、种族遗传因素、体质因素、慢性劳损、关节过度活动及气候因素有关；继发性OA的发生与关节内的直接创伤、下肢力线不正、关节面对合不良、关节内结构紊乱及关节不稳定等有关。在这些致病因素的影响下，关节软骨发生了退行性改变。关于OA的发病机制，国内外进行了大量的研究，认为主要是血液循环障碍、自由基、微量元素、自身免疫反应、细胞因子、酶、激素、前列腺素等导致软骨细胞和软骨基质的退变而引起本病。关节软骨变性、破坏之后，软骨下骨增生，逐渐出现关节滑膜和关节囊的增生肥厚，继发性滑膜炎，进一而关节羹纤维化甚至孪缩，关节呈现纤维性强直．临床上早期表现为愎骨下疼痛，关节反复肿胀，晚期可出现关节畸形。检查时可见肪骨深面及膝关节周围压痛，关节活动轻度或中度受限，严重者可出现膝内翻或外翻畸形。早期X线片无明显改变，以后逐渐发现关节间隙变窄及骨膺损，伴有不同程度的骨质增生。中医认为，膝OA是“痹症”中的特殊症型即“骨痹”，根据其病因病机，可分为寒湿阻络、痰瘀交阻、肝肾不足、肾阳不足四种类型。因此，临床拍疗以滋补肝肾、祛除风湿、通络止痛、活血化瘀为法，进行辨症施泊。而外治法如熏洗法、敷贴法、中药离子导入等，则是从活血通络、温经止痛人手。此外，运用舒筋按摩手法及针灸等亦取得了较好的疗效。西药方面，非类固醇类抗炎药（NSAID）是目前临床上泊疗骨性关节炎最常用的药物，但可引起胃及十二指肠汲疡和肾功能损害。目前，人们研制出选捍性的COX－2抑制剂如美洛昔康，仅抑制COX－2的合成，从而减少了副反应的发生；软骨保护剂如硫酸葡萄槽胺则通过促进关节软骨的修复来达到治疗的目的。但单纯的药物疗法只能改变早期或中期骨性关节 炎的症状，且停药后奔易复发，对于疼病严重、功能明显受限者，可考虑 行手术治疗。 第三部分是临床研究。将符合纳人标准的忌者随机分为治疗组和对照组，分别记录其治疗前后疼痛、步行能力计分以及血浆m巳的变化。结果 发现，两组治疗前的症状体征计分和隅马水平经统计学处理均无显著性差 异，说明两组具有可比性；分别使用龙鳖胶囊和扶他林治疗6周后再测上 述指标，则差异显著，两种药物均有较好的疗效；但是，从泊疗过程中的 复发率、失访率以及副反应的发生率等因素来看，龙鳖肢羹明显较扶他林 的剐作用小，复发率低，而失访率相近。同时，较为详细的临床资料显示， 大部分复发和失访的病例均属病程较长、X线分级为Ill级或以上者。因此， 龙鳖胶囊和扶他林均适用于早、中期骨性关节炎的患者，对晚期患者的疗 2 中 文拘要效尚不满意。 第四部分为讨论部分。首先对临床研究的结果进行分析，发现龙鳖胶囊和扶他林在治疗骨性关节炎时疗效相近，但龙鳖胶囊具有副作用小优点，宜于长期服用。其次阐述了龙鳖胶囊的组方依据及方药分析，认为本病辩证属本虚标实，肾阳不足为本，寒湿阻络为标，虚实夹杂。故临床治疗时以补肾助阳、通络止捅为泊则，采用巴就、仙茅、全蝎、蜈蚣、祁蛇等药物，标本兼顾，治疗骨痹尤其是肾阳虚兼寒湿阻络者效果良好。还对龙鳖胶囊的治疗机制进行了椎测，认为它能够促进软骨修复和抑制炎症反应。最后指出了本研究所存在的问题主要有症状体征的量化难以真正客观化、检测指标PGB。不能难确地反应出药物的疗效、临床研究中患者的依从性难以控制、龙鳖胶羹的具体作用机理不甚清楚等，有待进一步研究解决。更多还原

【Abstract】 Osteoarthritis (OA) of knee is a chronic disease which badly harms health of the old. The patients mainly suffer from pain, stiffness and limitation of activity. OA is the same meaning as “bi of bones” in traditional Chinese medicine. Its characteristic is that articular cartilage appears primary or secondary degeneration, with hypcrplasia of the bone under cartilage, but the cause and pathogenesis of OA are not completely clear yet, there is no satisfying way to treat OA besides replacement of knee joint in the present medicine. However some traditional Chinese medicine (TCM) maybe have a good effect. Long-We Capsule is an agent of TCM, which has been used for a long time in the department of orthopaedics of Guang Dong provincial hospital of TCM. Its effect has been proved to be satisfying by many years’clinical application, and its side-effect is tiny. This thesis is based on the studies about OA which have been finished by traditional Chinese medicine and Western medicine. In order to explore the pathogenesis of OA and the effect of Long-Bie capsule, we carry out this clinical study-“the curative effect of Long-Bie capsule to OA of knee” The first part is preface which has been divided into two sections. The former summarizes the causes, pathogenesis, diagnosis and treatment of OA; the later discusses regulation of prostaglandin (PG) and the relation between PG and OA. PG plays an important role and its density changes accordingly during the course of OA. So we take PG as an index to reflect the progress of OA. The second part is study of correlative literature. In this part we summarize the domestic and foreign studies during the latest several years. The defining and meaning of OA is explained in details, as is adopted by all that OA is caused by primary and secondary pathogeny. The primary pathogeny is related to age, sex, occupation, race, genetic factor, constitution, chronic strain, over-activity of joint and climate, etc. The second pathogeny is related to direct wound in the joint, inclined strength line, bad correspondence between two articular surface, confused structure within joint, joint instability. etc. These etiological factors make articular cartilage degenerate. Pathogenesis of OA is degeneration of cartilage cell and stroma caused by the following factors: stasis of blood circulation, free radical, microelement, autoimmune reaction, cytokine, enzyme, hormone, prostaglandin, etc. After articular cartilage degenerates and destroys, the bone below it starts to grow in excess, then synovium and capsule of joint becomes plump gradually, synovitls happens later, step by step articular capsule presents fibrosis even contracture, at last the joint presents fibrous ankylosis. In early period the clinical situation of OA is pain under patella, the suffering joint swells time after time, in late period deformity maybe appears. During clinical examination tenderness of knee is found on the inner surface of patella or round the joint, its motion is lightly or moderately limited, but in those serious cases varum or exstrophy exists usually. In the initial stage no evident change is found by X-ray, then joint space gets narrow gradually and bone wears out, with hyperplasia of bone. It is considered by TCM that OA of knee is the special type of “bi” namely “bi of bones” According to its cause and mechanism OA can be divided into the following types: coldness and dampness blocking collaterals, phlegm and dampness blocking together, deficiency of liver and kidney, deficien更多还原