桂枝芍药知母汤治疗类风湿关节炎疗效及对生存质量影响的研究
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摘要
类风湿关节炎是一种以关节滑膜炎症为特征的慢性全身性自身免疫性疾病,滑膜炎可反复发作,导致关节软骨及骨质破坏,最终导致关节畸形及功能障碍。中医认为本病是因人体正气不足,风寒湿热等外邪侵袭机体,闭阻经脉而出现以肢体关节肌肉疼痛、麻木、肿胀、屈伸不利,甚至关节变形为特征的一种疾病,因其病程长,难以治愈,故中医称为“顽痹”、“旭痹”、“白虎历节”等。
类风湿关节炎(RA)是一种系统性、多关节慢性炎症为特点的自身免疫性疾病,常伴随关节损害和残疾。RA的发现已有200年的历史,治疗的药物和方法也是层出不穷。从一开始单纯限于镇痛消炎的对症治疗,到后来使用改变病情作用的药物,现在已经发展到应用针对于类风湿关节炎发病有关的免疫环节的药物。临床疗效有了一定的提高,不少患者不仅症状减轻,也因关节功能的改善而提高了生活质量。治疗的目的主要是为了减轻疼痛控制病情发展,阻止发生不可逆的骨改变,尽可能保护关节和肌肉的功能,改善患者的生活质量。但目前的医疗水平,对RA仍不能达到治愈,只能达到减慢病情进展的目的,研究安全有效的治疗RA药物迫在眉睫。
RA属中医痹症范畴,历代医家对其发病机理多有论述。早在《素问·痹论》中就有“风寒湿三气杂至,合而为痹”之说。《儒门事亲》则认为“痹病以湿热为源,风寒为兼,三气合而为痹”。《金匮要略·中风历节病脉证并治第五》从正气不足的角度认识痹症的病机“寸口脉沉而弱……故曰历节”。《类证治裁·痹证》云:“诸痹……良由营卫先虚,腠理不密,风寒湿乘虚内袭,正气为内所阻,不能宣汗,因而留滞,气血凝涩,久而成痹。”又如《医学绳墨·痹》曰:“大率痹由气血虚弱,荣卫不能和通,致令三气乘于腠理之间。”近现代医家对类风湿关节炎的中医病因病机认识都有自己的观点,但多数医家认同本病“正虚外感”这一病机,所谓正虚是指因机体正气不足、腠理不密、卫外不固等虚不抗邪而发病;所谓外感是指机体感受外界的风、寒、湿、热之邪气,从而引发痹病。本病是本虚标实之证,虚实夹杂是其特点,以气血不足、肝肾亏虚为本,外邪侵袭、湿邪壅滞及痰瘀互结为标。其中湿滞、痰瘀既是病理产物,又是致病因素。
祖国医学治疗类风湿关节炎的药物丰富多彩,最常见的是辨证论治,但往往以经典名方作为基础方进行加减变化,而使用最多的就是出自《金匮要略》的桂枝芍药知母汤,桂枝芍药知母汤,原方出自《金匮要略·中风历节病脉证治》篇,由桂枝、白芍、甘草、麻黄、生姜、白术、知母、防风、附子组成,具有祛风除湿、温经散寒、滋阴清热之功效,主治风湿历节。其条文为:“诸肢节疼痛,身体魁赢,脚肿如脱,头眩短气,温温欲吐,桂枝芍药知母汤主之。”方中桂枝、麻黄、防风温散寒湿于表,芍药、知母和阴行痹于里,白术、附子助阳除湿,生姜、甘草和胃调中。同时麻、桂得术能兼除表里之湿,合以附子可温经复阳;生姜既助麻黄散寒,又助白术、甘草和中。诸味相伍,合而用之,则表里兼顾,风湿俱去,有温散而不伤阴,养阴而不碍阳之妙。
对桂枝芍药知母汤治疗类风湿关节炎的研究很多,有实验研究,也有临床研究,但临床研究多采用比较单一的观察指标,有的只观察临床症状,有的结合实验室指标,但针对类风湿关节炎中医治疗,采用国际公认的疗效观察指标研究不多,对中医药治疗类风湿关节炎生存质量的研究也较少。
我们的研究就是针对以上不足,选择了符合诊断标准的类风湿关节炎患者50例,桂枝芍药知母汤颗粒治疗3个月,采用DAS-28判断疗效,并采用HAQ评价治疗对患者生存质量的影响。希望我们的研究对类风湿关节炎的中医药治疗提供证据。
1、方法
在两个中医门诊入组50例符合诊断标准、纳入标准、排除标准的类风湿关节炎患者;桂枝芍药知母汤颗粒治疗3个月,分别在治疗前、治疗一个月、治疗两个月、治疗结束时对患者的DAS-28进行评分;采用HAQ问卷,分别在治疗前、治疗一个月、治疗两个月、治疗结束时对桂枝芍药知母汤颗粒对类风湿关节炎患者生存质量HAQ评分的影响进行研究。
2、结果
2.1临床症状改善情况显示,在治疗一个月后,患者的关节触痛有所改善,但与治疗前相比,差异没有显著意义(P＞0.05);两个月后,关节触痛继续减轻,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,关节触痛明显缓解,统计学比较有显著性差异(P＜0.01)。有关关节肿胀,治疗结果显示,在治疗一个月后,患者的关节肿胀有所改善,但与治疗前相比,差异已有显著意义(P＜0.05);两个月后,关节肿胀继续减轻,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,关节肿胀明显缓解,统计学比较有显著性差异(P＜0.01)。
2.2研究显示,在治疗一个月后,患者的血沉有所下降,与治疗前相比,差异有显著意义(P＜0.05);两个月后,血沉继续下降,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,血沉明显降低,统计学比较有显著性差异(P＜0.01)。
2.3研究显示,在治疗一个月后,患者的整体健康状态有所改善,与治疗前相比,差异有显著意义(P＜0.05);两个月后,整体健康状态继续改善,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,整体健康状态明显好转,统计学比较有显著性差异(P＜0.01)。
2.4在治疗一个月后,患者的DAS-28评分有所改善,但与治疗前相比,差异没有显著意义(P＞0.05);两个月后,DAS-28评分继续减轻,与治疗前相比,差异有显著意义(P＜0.05),治疗结束时,DAS-28评分明显缓解,统计学比较有显著性差异(P＜0.01)。
2.5本研究发现,在治疗一个月后,患者的残疾指数和不适指数有下降,患者的HAQ评分有所改善,但与治疗前相比,差异没有显著意义(P＞0.05);两个月后,残疾指数明显下降,与治疗前比较,差异显著(P＜0.01),不适指数仍没有差异,HAQ评分继续减轻,与治疗前相比,差异有显著意义(P＜0.05),治疗结束时,残疾指数、不适指数及HAQ评分均明显下降,统计学比较有显著性差异(P＜0.01)。
3、结论
3.1桂枝芍药知母汤颗粒有效改善患者关节肿痛。
桂枝芍药知母汤是治疗“历节”的千古名方,“历节”的主要症状就包括“诸肢节肿痛”,关节肿胀是类风湿关节炎最客观的体征,而关节疼痛是患者最痛苦的所在。实验研究也表明,桂枝芍药知母汤明显抑制醋酸所致小鼠扭体反应和大鼠棉球肉芽肿组织增生,降低小鼠腹腔毛细血管通透性,显著抑制佐剂性关节炎大鼠原发性足肿胀及继发性关节炎,机理研究表明桂枝芍药知母汤可明显降低佐剂性大鼠炎性组织中前列腺素的含量,同时还显著抑制炎症反应时的白细胞游走。方中桂枝、附子温经散寒止痛,麻黄、生姜祛风散寒,通阳开痹,使风寒湿邪从表而散,给邪以出路,白术、防风祛风除湿,知母、芍药养阴清热,甘草与白芍缓急止痛,并能调和药性。诸药合用,能较好的止痛、消肿。临床研究表明,有于类风湿关节炎的发病是一个慢性长期反复的过程,所以不论中西药的治疗,疗程都是长期的,本研究表明,治疗一个月后,关节肿胀就明显减轻,证明桂枝芍药知母汤具有较好的消肿作用,而对关节触痛的影响,两个月时有统计学意义,说明桂枝芍药知母汤止痛作用在两个月左右开始起效。
3.2桂枝芍药知母汤颗粒明显降低血沉,减轻炎症反应。
血沉是反映类风湿关节炎活动性的有效实验室指标,虽然特异性不强,但排出其他如感染、肿瘤等情况外,一般可以反映类风湿关节炎的活动情况,结合临床表现则说服力更强。本研究显示,桂枝芍药知母汤颗粒治疗一个月后,血沉就有下降,与治疗前相比有统计学意义。说明桂枝芍药知母汤除了能有效改善临床症状外,对改善实验室指标也有作用,且用药一月就有效果,比较一般三至六个月起效的西药慢作用药,如甲氨喋呤、来氟米特等,具有起效快的优势。
3.3桂枝芍药知母汤颗粒有效改善患者整体健康情况。
研究发现,一般在用药一个月后,患者的疼痛和肿胀都有好转,因此,没有疼痛的困扰,患者的生活质量可以提高,随着肿胀的好转,患者的关节功能逐步改善,患者的活动半径逐步增大,从生理到心理的质量提高都会改善,所以患者的整体健康状况逐步改善,随着治疗的进展,各项指标都在逐渐改善中。
3.4桂枝芍药知母汤颗粒明显改善患者DAS-28评分,减轻关节炎活动程度。
DAS-28是国际风湿学界常用的判断类风湿关节炎活动程度的综合指标,也是评价治疗类风湿关节炎药物的疗效标准之一,本研究采用DAS-28作为判断桂枝芍药知母汤治疗类风湿关节炎的疗效判定指标,发现,治疗2个月后,DAS-28明显改善,与治疗前比较有统计学差异。充分证明桂枝芍药知母汤是治疗类风湿关节炎的有效药物。
3.5桂枝芍药知母汤颗粒降低患者HAQ评分,提高患者的生存质量。
桂枝芍药知母汤对患者生活质量的改善是和对临床症状的改善一致的。治疗一个月后,由于关节触痛和关节肿胀都好转,患者的活动半径增加,以前不能完成的动作己能自己完成,如上肢功能的改善,肩、肘功能好转,患者就能自己穿衣服,能自己洗澡,且擦干身体,腕、掌指、指间关节功能改善,患者就能系鞋带和纽扣,能端一满杯水送到嘴边,能开关水龙头或者瓶塞,髋、膝功能改善,患者就能自己上床,下床,能在室外的平地上行走,能蹲下,拾起地上的衣服,能上下车,等等。两个月时,由于功能的改善,患者的残疾指数与治疗前比较,差异显著。
由于生活能力的提高,患者觉得能减轻周围人的负担,能被人需要,所以心情好转,逐渐喜爱自己所从事的事情,减轻紧张或焦虑,减轻烦躁不安、能镇静,伤心或情绪低落、难以兴奋等不良情绪逐步减轻,身体的不适减轻,心理的负担也减轻,所以HAQ评分随着身体症状的好转,而逐步好转。目前各项研究显示,药物治疗只能使类风湿关节炎的炎症得到控制,对已残废的关节不能修复,对已丧失的功能,不能逆转,所以与临床症状相比,患者的不适指数恢复是一个更费时的过程,由于部分功能永远不能回复,所以患者的部分不适很难消除。
综上所述,我们研究发现,桂枝芍药知母汤治疗类风湿关节炎在一个月左右就能减轻关节肿胀,两个月左右明显减轻关节触痛,一个月左右就能改善血沉,改善患者的整体功能评价,改善患者的DAS-28评分,两个月左右时各项指标明显改善,除不适指数外,均与治疗前有显著差异。治疗3个月后,所有观察指标均明显改善。表明,在止痛方面,可起效较慢,但对于其他指标,起效均比传统西药要快。
Rheumatoid Arthritis(RA) is a chronic systematic autoimmune disease with the feature of arthrosynovitis which may occur repeatedly,cause articular cartilage and bone destruction and finally cause joint abnormality and dysfunction.Chinese Medicine holds that the pathogen is deficiency of healthy qi and invasion of external evils like wind cold,dampness and heat,etc,which cause the meridian and collateral obstruction.The joints and muscles may feel pain,numb,swollen and inflexible,and even take dysarthosis.As the course is long and it' s hard to cure,Chinese Medicine calls it obstinate arthralgia, severe and migratory arthralgia,etc.
As a systematic autoimmune disease with the characteristics of multi-joint chronic inflammation,it is often accompanied by joint injury and deformity. It is 200 years since the discovery of RA,medicine and therapies for its treatment are numerous,starting from the therapy limited to pain and inflammation relief originally,to medicine which may change the illness condition and now to the related immunological medicine.The clinical efficacy is improved.Many patients have relieved symptoms and their life quality is also improved for the amelioration of joint function.The purpose of treatment is to control pain and disease development,prevent the irreversible bone change,protect the joint and muscle function and improve the patients' life quality.But considering the current medical level,RA can' t be cured and can just be slowed.It' s urgent to make research on safe and efficient medicine for RA.
RA is classified as arthromyodynia of Chinese Medicine and doctors of generations have discussions on its pathogenesis.In Su Wen,it says that wind, cold and dampness cause the arthromyodynia.Confucian' s Duties to Their Parents says the origin of arthromyodynia is dampness,heat and cold combined together.Golden Chamber says the Cunkou pulse is heavy and weak,so the healthy qi is not sufficient and arthromyodynia is caused.Classified Treatment and Syndrome Differentiation says all arthromyodynia is caused because the yingqi and weiqi are deficient,the interspaces of skin and muscles are loose,the wind,coldness and dampness attack,the healthy qi is obstructed,the sweat can' t be excluded and it stagnates,the qi and blood stagnate and all the factors mentioned cause arthromyodynia.Thread Ink of Medical Circle says generally the arthromyodynia is caused by deficient qi and blood and the nourishing qi is not smooth,therefore the three qi enter the interspaces of skin and muscles.Modern doctors have their own opinions about RA' s pathogenesis and etiology from the angle of Chinese Medicine:however most doctors agree that the pathogenesis of RA is the healthy qi asthenia and external invasion.The healthy qi asthenia refers to the fact that healthy qi is deficient,the interspace between skin and muscles and can' t defend the external evils.The external invasion refers to the coldness,wind, dampness and heat.This disease is of deficient origin and sthenia syndromes. Damp stagnation and sputum is both the pathological outcome and the pathogenesis factors.
In Chinese Medicine,there is a variety of medicine for RA and the most commonly seen is syndrome differentiation which is usually the modification of classical prescriptions.The most frequently used is Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction originally from Golden Chamber consisting of ramulus cinnamomi,white peony root,sweet root,joint fir,rhizome, atractylodes marcrocephala,anemarrhenae,saposhnikoviae and aconite root. It can diminish the wind and dampness,warm the meridians and disperse coldness, nourish yin and get rid of heat.Its indication is RA.The original text says that if all joints feel pain,the body is weak,the feet are swollen,and the person feels dizzy and short of breath and wants to vomit,it' s suitable to use Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction.Ramulus cinnamomi, joint fir and saposhnikoviae can disperse coldness and dampness.Paeonia and anemarrhenae can smooth the arthralgia spasm.Atractylodes macrocephala and aconite root can help nourish yang and diminish dampness.Rhizoma and sweet root can ameliorate stomach and the internal organs.Joint fir and ramulus cinnamomi can diminish the dampness of the internal and external part with atractylodes macrocephala and can warm meridians and recover yang with aconite root.Rhizoma can help joint fir to disperse coldness and help atractylodes macrocephala and sweet root to ameliorate the internal organs.These elements used together can take care of both the internal and external parts,diminish wind and dampness,warm but not hurt yin and nourish yin not hurt yang.
There are both experimental and clinical studies on RA treatment with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction.However the clinical study mainly adopts simple observation indexes,some just observing clinical syndromes,some considering the lab indexes.About the Chinese Medicine treatment of RA,few researches adopt internationally recognized efficacy observation indexes,and few focus on the life quality of RA with Chinese Medicine treatment.
Considering the deficiency mentioned above,we selected 50 cases consistent with the diagnosis criteria of RA,give treatment for 3 months with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules,adopt DAS-28 to judge the efficacy and adopt HAO to evaluate the effect of treatment on patients' life quality.We hold the hope that our research may provide proof for Chinese Medicine treatment of RA.
1.Methods
Select 50 patients consistent with the diagnostic,inclusion and exclusion criteria and group them into two Chinese Medicine clinics.Give treatment for 3 months with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules and score the DAS-28 before treatment,one and two months after treatment and at the end of the treatment respectively.Score the HAQ of RA patients' life quality before treatment,one and two months after treatment and at the end of the treatment respectively.
2.Result
Clinical syndrome improvement shows that after one month' s treatment,the patients' joint pain ameliorates,but there is no statistical significance (P＞0.05) compared with that before treatment;two months later,the joint haphalgesia continuously lessens and there' s statistical significance (P＜0.01) compared with that before treatment;at the end of the treatment, the joint haphalgesia obviously ameliorates and there' s statistical significance(P＜0.01).About arthrocele,the result shows that after one month' s treatment,the patients' arthrocele ameliorates,but there is statistical significance(P＜0.05) compared with that before treatment;two months later,the arthrocele continuously lessens and there' s statistical significance(P＜0.01) compared with that before treatment;at the end of the treatment,the arthrocele obviously ameliorates and there' s statistical significance(P＜0.01).
The result shows that after one month' s treatment,the patients' blood sedimentation drops,and there is statistical significance(P＜0.05) compared with that before treatment;two months later,the blood sedimentation continuously drops and there' s statistical significance (P＜0.01) compared with that before treatment;at the end of the treatment, the blood sedimentation obviously drops and there' s statistical significance(P＜0.01).
The result shows that after one month' s treatment,the patients' general health ameliorates,and there is statistical significance(P＜0.05) compared with that before treatment;two months later,the general health continuously ameliorates and there' s statistical significance(P＜0.01) compared with that before treatment;at the end of the treatment,the general health obviously ameliorates and there' s statistical significance(P＜0.01). After one month' s treatment,the patients' DAS-28 score improves,but there is no statistical significance(P＞0.05) compared with that before treatment;two months later,the DAS-28 score improves continuously and there' s statistical significance(P＜0.01 ) compared with that before treatment;at the end of the treatment,the DAS-28 score improves obviously and there' s statistical significance(P＜0.01).
The result shows that after one month' s treatment,the patients' deformity and discomfort index drops,and the HAQ score improves,but there is no statistical significance(P＞0.05) compared with that before treatment;two months later,the deformity index obviously drops and there' s statistical significance(P＜0.01) compared with that before treatment;the discomfort index has no difference,the HAO score continuously drops and has statistical significance(P＜0.05);at the end of the treatment,the deformity index,the discomfort index and HAQ score obviously drop and there' s statistical significance(P＜0.01).
3.Conclusion
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Effectively Ameliorate Patients' Joint Swelling and Pain
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction is a classical famous prescription for RA.Arthrocele is the most objective sign of RA and causes the greatest pain of patients.Lab research also shows that Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction can obviously inhibit the mice' s writhing response caused by acetic acid and rats' cotton ball granuloma hyperblastosis,lower the mice' s abdomen cavity capillary permeability,and inhibit adjuvanticity arthritis,rats' primary forced foot and secondary arthritis.Mechanism research shows that Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction can obviously lower the prostaglandin content of rats' adjuvanticity inflammatory textures,and inhibit the leukoplania of inflammatory reaction.In the prescription,ramulus cinnamomi and aconite root can warm meridians,disperse coldness and stop pain;joint fir and rhizome can disperse wind and coldness,activate yang and smoothing spasm,and disperse cold wind and dampness from the surface;atractylodes macrocephala and saposhnikoviae root can diminish wind and dampness; anemarrhenae and paeonia can nourish yin and diminish heat;sweet root and paeonia alba can stop pain and ameliorate the drug property.All elements combined can effectively diminish pain and swelling.Clinical research shows that since RA is a long-term chronic repeated disease,so the treatment course is long with no matter Chinese or Western Medicine treatment.One month' s treatment later,the arthrocele lessens and it proves that Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction has good function of swelling diminishing. About joint haphalgesia,there' s statistical significance after two months' treatment which indicates that the analgesic effect of Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction takes place around two months.
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Can Effectively Lower the Blood Sedimentation and Lessen Inflammatory Reaction
Blood sedimentation is an effective lab index to show the RA activity. Though it doesn't have strong specificity,but if the other conditions like infection and tumor are excluded,it can reflect the activity of RA.It' s more persuasive if combined with clinical manifestation.This research shows that after one month' s treatment with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction granules,the blood sedimentation drops and there' s statistical significance compared with that before treatment.It shows that besides effectively ameliorating clinical syndromes,Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction can also improve the lab index.Its effective after just one month and it' s more efficient than some Western drugs like Methotrexate and Leflunomide which takes effect after 3 to 6 months. Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Effectively Improve Patients' General Health
Research shows that after one month' s intake of medicine,patients' pain and swelling improve and life quality improves.With improvement of swelling, the joint function improves and radius of action is enlarged and patients' physiological and psychological condition improves,so their general health improves.With treatment,each index is in the process of improvement.
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Effectively Improve Patients' DAS-28 Score and Lessen Arthritis Activity
DAS-28 is a comprehensive index to judge the RA activity in the international RA field and also an efficacy criterion to evaluate RA drug. This research takes DAS-28 to judge the efficacy of Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules in RA treatment.It is found that after 2 months,DAS-28 obviously improves and has statistical difference compared with that before treatment which fully proves that Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction is an effective medicine for RA.
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Lower Patients' HAQ Score and Improve Life Quality
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction can improve both the life quality and clinical syndrome consistently.After one month' s treatment,because of the improvement of joint haphalgesia and arthrocele, the patients' activity radius enlarges and they can finish some task which they couldn't do before.For example,with the improvement of upper extremity function and the shoulder and elbow function,the patients can put on clothes, bathe and wipe dry their bodies by themselves;with the improvement of wrist, finger and articulations interphalangeae patients can tie shoelace and buttons, take a glass of water to the mouth,and can open or close the tap or cork; with the improvement of coax and knee function,patients can get on or off bed by themselves and can walk on the outdoor ground,squat down,pick up the clothes on the floor,get on or off cars,etc.After two months' treatment, with the function improvement,there' s significant difference in deformity index compared with that before treatment.
With life ability improvement,patients feel they can relieve their families' burdens and are needed by others,so their mood improves and can gradually like what they are doing.They can lessen anxiety or dysphoria,calm down and lessen adverse moods like sadness or depression.By lessening discomfort of body,their psychological burden also lessens,so the HAQ Score improves with the recovery of physical syndromes.The current research shows that medical treatment can only inhibit the inflammation of RA but can' t repair the deformed joints and can' t reverse the lost function.So compared with clinical syndromes,the discomfort index takes longer time.Since part of the function can' t be repaired,the patients' discomfort is difficult to diminish.
Generalizing what we mention above,we find that Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction can lessen arthrocele after one month' s treatment,obviously lessen the joint haphalgesia around two months and improve blood sedimentation around one month.It can improve patients' general evaluation of function and the DAS-28 score.Around two months' treatment,except discomfort index,each index is improved obviously around two months compared with those before treatment.After 3 months' treatment, all indexes are obviously improved.It shows that in analgesia,it takes effect slowly.But considering the other indexes,it is quicker in taking effect than Western Medicine.
类风湿关节炎(RA)是一种系统性、多关节慢性炎症为特点的自身免疫性疾病,常伴随关节损害和残疾。RA的发现已有200年的历史,治疗的药物和方法也是层出不穷。从一开始单纯限于镇痛消炎的对症治疗,到后来使用改变病情作用的药物,现在已经发展到应用针对于类风湿关节炎发病有关的免疫环节的药物。临床疗效有了一定的提高,不少患者不仅症状减轻,也因关节功能的改善而提高了生活质量。治疗的目的主要是为了减轻疼痛控制病情发展,阻止发生不可逆的骨改变,尽可能保护关节和肌肉的功能,改善患者的生活质量。但目前的医疗水平,对RA仍不能达到治愈,只能达到减慢病情进展的目的,研究安全有效的治疗RA药物迫在眉睫。
RA属中医痹症范畴,历代医家对其发病机理多有论述。早在《素问·痹论》中就有“风寒湿三气杂至,合而为痹”之说。《儒门事亲》则认为“痹病以湿热为源,风寒为兼,三气合而为痹”。《金匮要略·中风历节病脉证并治第五》从正气不足的角度认识痹症的病机“寸口脉沉而弱……故曰历节”。《类证治裁·痹证》云:“诸痹……良由营卫先虚,腠理不密,风寒湿乘虚内袭,正气为内所阻,不能宣汗,因而留滞,气血凝涩,久而成痹。”又如《医学绳墨·痹》曰:“大率痹由气血虚弱,荣卫不能和通,致令三气乘于腠理之间。”近现代医家对类风湿关节炎的中医病因病机认识都有自己的观点,但多数医家认同本病“正虚外感”这一病机,所谓正虚是指因机体正气不足、腠理不密、卫外不固等虚不抗邪而发病;所谓外感是指机体感受外界的风、寒、湿、热之邪气,从而引发痹病。本病是本虚标实之证,虚实夹杂是其特点,以气血不足、肝肾亏虚为本,外邪侵袭、湿邪壅滞及痰瘀互结为标。其中湿滞、痰瘀既是病理产物,又是致病因素。
祖国医学治疗类风湿关节炎的药物丰富多彩,最常见的是辨证论治,但往往以经典名方作为基础方进行加减变化,而使用最多的就是出自《金匮要略》的桂枝芍药知母汤,桂枝芍药知母汤,原方出自《金匮要略·中风历节病脉证治》篇,由桂枝、白芍、甘草、麻黄、生姜、白术、知母、防风、附子组成,具有祛风除湿、温经散寒、滋阴清热之功效,主治风湿历节。其条文为:“诸肢节疼痛,身体魁赢,脚肿如脱,头眩短气,温温欲吐,桂枝芍药知母汤主之。”方中桂枝、麻黄、防风温散寒湿于表,芍药、知母和阴行痹于里,白术、附子助阳除湿,生姜、甘草和胃调中。同时麻、桂得术能兼除表里之湿,合以附子可温经复阳;生姜既助麻黄散寒,又助白术、甘草和中。诸味相伍,合而用之,则表里兼顾,风湿俱去,有温散而不伤阴,养阴而不碍阳之妙。
对桂枝芍药知母汤治疗类风湿关节炎的研究很多,有实验研究,也有临床研究,但临床研究多采用比较单一的观察指标,有的只观察临床症状,有的结合实验室指标,但针对类风湿关节炎中医治疗,采用国际公认的疗效观察指标研究不多,对中医药治疗类风湿关节炎生存质量的研究也较少。
我们的研究就是针对以上不足,选择了符合诊断标准的类风湿关节炎患者50例,桂枝芍药知母汤颗粒治疗3个月,采用DAS-28判断疗效,并采用HAQ评价治疗对患者生存质量的影响。希望我们的研究对类风湿关节炎的中医药治疗提供证据。
1、方法
在两个中医门诊入组50例符合诊断标准、纳入标准、排除标准的类风湿关节炎患者;桂枝芍药知母汤颗粒治疗3个月,分别在治疗前、治疗一个月、治疗两个月、治疗结束时对患者的DAS-28进行评分;采用HAQ问卷,分别在治疗前、治疗一个月、治疗两个月、治疗结束时对桂枝芍药知母汤颗粒对类风湿关节炎患者生存质量HAQ评分的影响进行研究。
2、结果
2.1临床症状改善情况显示,在治疗一个月后,患者的关节触痛有所改善,但与治疗前相比,差异没有显著意义(P＞0.05);两个月后,关节触痛继续减轻,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,关节触痛明显缓解,统计学比较有显著性差异(P＜0.01)。有关关节肿胀,治疗结果显示,在治疗一个月后,患者的关节肿胀有所改善,但与治疗前相比,差异已有显著意义(P＜0.05);两个月后,关节肿胀继续减轻,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,关节肿胀明显缓解,统计学比较有显著性差异(P＜0.01)。
2.2研究显示,在治疗一个月后,患者的血沉有所下降,与治疗前相比,差异有显著意义(P＜0.05);两个月后,血沉继续下降,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,血沉明显降低,统计学比较有显著性差异(P＜0.01)。
2.3研究显示,在治疗一个月后,患者的整体健康状态有所改善,与治疗前相比,差异有显著意义(P＜0.05);两个月后,整体健康状态继续改善,与治疗前相比,差异有显著意义(P＜0.01),治疗结束时,整体健康状态明显好转,统计学比较有显著性差异(P＜0.01)。
2.4在治疗一个月后,患者的DAS-28评分有所改善,但与治疗前相比,差异没有显著意义(P＞0.05);两个月后,DAS-28评分继续减轻,与治疗前相比,差异有显著意义(P＜0.05),治疗结束时,DAS-28评分明显缓解,统计学比较有显著性差异(P＜0.01)。
2.5本研究发现,在治疗一个月后,患者的残疾指数和不适指数有下降,患者的HAQ评分有所改善,但与治疗前相比,差异没有显著意义(P＞0.05);两个月后,残疾指数明显下降,与治疗前比较,差异显著(P＜0.01),不适指数仍没有差异,HAQ评分继续减轻,与治疗前相比,差异有显著意义(P＜0.05),治疗结束时,残疾指数、不适指数及HAQ评分均明显下降,统计学比较有显著性差异(P＜0.01)。
3、结论
3.1桂枝芍药知母汤颗粒有效改善患者关节肿痛。
桂枝芍药知母汤是治疗“历节”的千古名方,“历节”的主要症状就包括“诸肢节肿痛”,关节肿胀是类风湿关节炎最客观的体征,而关节疼痛是患者最痛苦的所在。实验研究也表明,桂枝芍药知母汤明显抑制醋酸所致小鼠扭体反应和大鼠棉球肉芽肿组织增生,降低小鼠腹腔毛细血管通透性,显著抑制佐剂性关节炎大鼠原发性足肿胀及继发性关节炎,机理研究表明桂枝芍药知母汤可明显降低佐剂性大鼠炎性组织中前列腺素的含量,同时还显著抑制炎症反应时的白细胞游走。方中桂枝、附子温经散寒止痛,麻黄、生姜祛风散寒,通阳开痹,使风寒湿邪从表而散,给邪以出路,白术、防风祛风除湿,知母、芍药养阴清热,甘草与白芍缓急止痛,并能调和药性。诸药合用,能较好的止痛、消肿。临床研究表明,有于类风湿关节炎的发病是一个慢性长期反复的过程,所以不论中西药的治疗,疗程都是长期的,本研究表明,治疗一个月后,关节肿胀就明显减轻,证明桂枝芍药知母汤具有较好的消肿作用,而对关节触痛的影响,两个月时有统计学意义,说明桂枝芍药知母汤止痛作用在两个月左右开始起效。
3.2桂枝芍药知母汤颗粒明显降低血沉,减轻炎症反应。
血沉是反映类风湿关节炎活动性的有效实验室指标,虽然特异性不强,但排出其他如感染、肿瘤等情况外,一般可以反映类风湿关节炎的活动情况,结合临床表现则说服力更强。本研究显示,桂枝芍药知母汤颗粒治疗一个月后,血沉就有下降,与治疗前相比有统计学意义。说明桂枝芍药知母汤除了能有效改善临床症状外,对改善实验室指标也有作用,且用药一月就有效果,比较一般三至六个月起效的西药慢作用药,如甲氨喋呤、来氟米特等,具有起效快的优势。
3.3桂枝芍药知母汤颗粒有效改善患者整体健康情况。
研究发现,一般在用药一个月后,患者的疼痛和肿胀都有好转,因此,没有疼痛的困扰,患者的生活质量可以提高,随着肿胀的好转,患者的关节功能逐步改善,患者的活动半径逐步增大,从生理到心理的质量提高都会改善,所以患者的整体健康状况逐步改善,随着治疗的进展,各项指标都在逐渐改善中。
3.4桂枝芍药知母汤颗粒明显改善患者DAS-28评分,减轻关节炎活动程度。
DAS-28是国际风湿学界常用的判断类风湿关节炎活动程度的综合指标,也是评价治疗类风湿关节炎药物的疗效标准之一,本研究采用DAS-28作为判断桂枝芍药知母汤治疗类风湿关节炎的疗效判定指标,发现,治疗2个月后,DAS-28明显改善,与治疗前比较有统计学差异。充分证明桂枝芍药知母汤是治疗类风湿关节炎的有效药物。
3.5桂枝芍药知母汤颗粒降低患者HAQ评分,提高患者的生存质量。
桂枝芍药知母汤对患者生活质量的改善是和对临床症状的改善一致的。治疗一个月后,由于关节触痛和关节肿胀都好转,患者的活动半径增加,以前不能完成的动作己能自己完成,如上肢功能的改善,肩、肘功能好转,患者就能自己穿衣服,能自己洗澡,且擦干身体,腕、掌指、指间关节功能改善,患者就能系鞋带和纽扣,能端一满杯水送到嘴边,能开关水龙头或者瓶塞,髋、膝功能改善,患者就能自己上床,下床,能在室外的平地上行走,能蹲下,拾起地上的衣服,能上下车,等等。两个月时,由于功能的改善,患者的残疾指数与治疗前比较,差异显著。
由于生活能力的提高,患者觉得能减轻周围人的负担,能被人需要,所以心情好转,逐渐喜爱自己所从事的事情,减轻紧张或焦虑,减轻烦躁不安、能镇静,伤心或情绪低落、难以兴奋等不良情绪逐步减轻,身体的不适减轻,心理的负担也减轻,所以HAQ评分随着身体症状的好转,而逐步好转。目前各项研究显示,药物治疗只能使类风湿关节炎的炎症得到控制,对已残废的关节不能修复,对已丧失的功能,不能逆转,所以与临床症状相比,患者的不适指数恢复是一个更费时的过程,由于部分功能永远不能回复,所以患者的部分不适很难消除。
综上所述,我们研究发现,桂枝芍药知母汤治疗类风湿关节炎在一个月左右就能减轻关节肿胀,两个月左右明显减轻关节触痛,一个月左右就能改善血沉,改善患者的整体功能评价,改善患者的DAS-28评分,两个月左右时各项指标明显改善,除不适指数外,均与治疗前有显著差异。治疗3个月后,所有观察指标均明显改善。表明,在止痛方面,可起效较慢,但对于其他指标,起效均比传统西药要快。
Rheumatoid Arthritis(RA) is a chronic systematic autoimmune disease with the feature of arthrosynovitis which may occur repeatedly,cause articular cartilage and bone destruction and finally cause joint abnormality and dysfunction.Chinese Medicine holds that the pathogen is deficiency of healthy qi and invasion of external evils like wind cold,dampness and heat,etc,which cause the meridian and collateral obstruction.The joints and muscles may feel pain,numb,swollen and inflexible,and even take dysarthosis.As the course is long and it' s hard to cure,Chinese Medicine calls it obstinate arthralgia, severe and migratory arthralgia,etc.
As a systematic autoimmune disease with the characteristics of multi-joint chronic inflammation,it is often accompanied by joint injury and deformity. It is 200 years since the discovery of RA,medicine and therapies for its treatment are numerous,starting from the therapy limited to pain and inflammation relief originally,to medicine which may change the illness condition and now to the related immunological medicine.The clinical efficacy is improved.Many patients have relieved symptoms and their life quality is also improved for the amelioration of joint function.The purpose of treatment is to control pain and disease development,prevent the irreversible bone change,protect the joint and muscle function and improve the patients' life quality.But considering the current medical level,RA can' t be cured and can just be slowed.It' s urgent to make research on safe and efficient medicine for RA.
RA is classified as arthromyodynia of Chinese Medicine and doctors of generations have discussions on its pathogenesis.In Su Wen,it says that wind, cold and dampness cause the arthromyodynia.Confucian' s Duties to Their Parents says the origin of arthromyodynia is dampness,heat and cold combined together.Golden Chamber says the Cunkou pulse is heavy and weak,so the healthy qi is not sufficient and arthromyodynia is caused.Classified Treatment and Syndrome Differentiation says all arthromyodynia is caused because the yingqi and weiqi are deficient,the interspaces of skin and muscles are loose,the wind,coldness and dampness attack,the healthy qi is obstructed,the sweat can' t be excluded and it stagnates,the qi and blood stagnate and all the factors mentioned cause arthromyodynia.Thread Ink of Medical Circle says generally the arthromyodynia is caused by deficient qi and blood and the nourishing qi is not smooth,therefore the three qi enter the interspaces of skin and muscles.Modern doctors have their own opinions about RA' s pathogenesis and etiology from the angle of Chinese Medicine:however most doctors agree that the pathogenesis of RA is the healthy qi asthenia and external invasion.The healthy qi asthenia refers to the fact that healthy qi is deficient,the interspace between skin and muscles and can' t defend the external evils.The external invasion refers to the coldness,wind, dampness and heat.This disease is of deficient origin and sthenia syndromes. Damp stagnation and sputum is both the pathological outcome and the pathogenesis factors.
In Chinese Medicine,there is a variety of medicine for RA and the most commonly seen is syndrome differentiation which is usually the modification of classical prescriptions.The most frequently used is Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction originally from Golden Chamber consisting of ramulus cinnamomi,white peony root,sweet root,joint fir,rhizome, atractylodes marcrocephala,anemarrhenae,saposhnikoviae and aconite root. It can diminish the wind and dampness,warm the meridians and disperse coldness, nourish yin and get rid of heat.Its indication is RA.The original text says that if all joints feel pain,the body is weak,the feet are swollen,and the person feels dizzy and short of breath and wants to vomit,it' s suitable to use Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction.Ramulus cinnamomi, joint fir and saposhnikoviae can disperse coldness and dampness.Paeonia and anemarrhenae can smooth the arthralgia spasm.Atractylodes macrocephala and aconite root can help nourish yang and diminish dampness.Rhizoma and sweet root can ameliorate stomach and the internal organs.Joint fir and ramulus cinnamomi can diminish the dampness of the internal and external part with atractylodes macrocephala and can warm meridians and recover yang with aconite root.Rhizoma can help joint fir to disperse coldness and help atractylodes macrocephala and sweet root to ameliorate the internal organs.These elements used together can take care of both the internal and external parts,diminish wind and dampness,warm but not hurt yin and nourish yin not hurt yang.
There are both experimental and clinical studies on RA treatment with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction.However the clinical study mainly adopts simple observation indexes,some just observing clinical syndromes,some considering the lab indexes.About the Chinese Medicine treatment of RA,few researches adopt internationally recognized efficacy observation indexes,and few focus on the life quality of RA with Chinese Medicine treatment.
Considering the deficiency mentioned above,we selected 50 cases consistent with the diagnosis criteria of RA,give treatment for 3 months with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules,adopt DAS-28 to judge the efficacy and adopt HAO to evaluate the effect of treatment on patients' life quality.We hold the hope that our research may provide proof for Chinese Medicine treatment of RA.
1.Methods
Select 50 patients consistent with the diagnostic,inclusion and exclusion criteria and group them into two Chinese Medicine clinics.Give treatment for 3 months with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules and score the DAS-28 before treatment,one and two months after treatment and at the end of the treatment respectively.Score the HAQ of RA patients' life quality before treatment,one and two months after treatment and at the end of the treatment respectively.
2.Result
Clinical syndrome improvement shows that after one month' s treatment,the patients' joint pain ameliorates,but there is no statistical significance (P＞0.05) compared with that before treatment;two months later,the joint haphalgesia continuously lessens and there' s statistical significance (P＜0.01) compared with that before treatment;at the end of the treatment, the joint haphalgesia obviously ameliorates and there' s statistical significance(P＜0.01).About arthrocele,the result shows that after one month' s treatment,the patients' arthrocele ameliorates,but there is statistical significance(P＜0.05) compared with that before treatment;two months later,the arthrocele continuously lessens and there' s statistical significance(P＜0.01) compared with that before treatment;at the end of the treatment,the arthrocele obviously ameliorates and there' s statistical significance(P＜0.01).
The result shows that after one month' s treatment,the patients' blood sedimentation drops,and there is statistical significance(P＜0.05) compared with that before treatment;two months later,the blood sedimentation continuously drops and there' s statistical significance (P＜0.01) compared with that before treatment;at the end of the treatment, the blood sedimentation obviously drops and there' s statistical significance(P＜0.01).
The result shows that after one month' s treatment,the patients' general health ameliorates,and there is statistical significance(P＜0.05) compared with that before treatment;two months later,the general health continuously ameliorates and there' s statistical significance(P＜0.01) compared with that before treatment;at the end of the treatment,the general health obviously ameliorates and there' s statistical significance(P＜0.01). After one month' s treatment,the patients' DAS-28 score improves,but there is no statistical significance(P＞0.05) compared with that before treatment;two months later,the DAS-28 score improves continuously and there' s statistical significance(P＜0.01 ) compared with that before treatment;at the end of the treatment,the DAS-28 score improves obviously and there' s statistical significance(P＜0.01).
The result shows that after one month' s treatment,the patients' deformity and discomfort index drops,and the HAQ score improves,but there is no statistical significance(P＞0.05) compared with that before treatment;two months later,the deformity index obviously drops and there' s statistical significance(P＜0.01) compared with that before treatment;the discomfort index has no difference,the HAO score continuously drops and has statistical significance(P＜0.05);at the end of the treatment,the deformity index,the discomfort index and HAQ score obviously drop and there' s statistical significance(P＜0.01).
3.Conclusion
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Effectively Ameliorate Patients' Joint Swelling and Pain
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction is a classical famous prescription for RA.Arthrocele is the most objective sign of RA and causes the greatest pain of patients.Lab research also shows that Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction can obviously inhibit the mice' s writhing response caused by acetic acid and rats' cotton ball granuloma hyperblastosis,lower the mice' s abdomen cavity capillary permeability,and inhibit adjuvanticity arthritis,rats' primary forced foot and secondary arthritis.Mechanism research shows that Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction can obviously lower the prostaglandin content of rats' adjuvanticity inflammatory textures,and inhibit the leukoplania of inflammatory reaction.In the prescription,ramulus cinnamomi and aconite root can warm meridians,disperse coldness and stop pain;joint fir and rhizome can disperse wind and coldness,activate yang and smoothing spasm,and disperse cold wind and dampness from the surface;atractylodes macrocephala and saposhnikoviae root can diminish wind and dampness; anemarrhenae and paeonia can nourish yin and diminish heat;sweet root and paeonia alba can stop pain and ameliorate the drug property.All elements combined can effectively diminish pain and swelling.Clinical research shows that since RA is a long-term chronic repeated disease,so the treatment course is long with no matter Chinese or Western Medicine treatment.One month' s treatment later,the arthrocele lessens and it proves that Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction has good function of swelling diminishing. About joint haphalgesia,there' s statistical significance after two months' treatment which indicates that the analgesic effect of Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction takes place around two months.
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Can Effectively Lower the Blood Sedimentation and Lessen Inflammatory Reaction
Blood sedimentation is an effective lab index to show the RA activity. Though it doesn't have strong specificity,but if the other conditions like infection and tumor are excluded,it can reflect the activity of RA.It' s more persuasive if combined with clinical manifestation.This research shows that after one month' s treatment with Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction granules,the blood sedimentation drops and there' s statistical significance compared with that before treatment.It shows that besides effectively ameliorating clinical syndromes,Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction can also improve the lab index.Its effective after just one month and it' s more efficient than some Western drugs like Methotrexate and Leflunomide which takes effect after 3 to 6 months. Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Effectively Improve Patients' General Health
Research shows that after one month' s intake of medicine,patients' pain and swelling improve and life quality improves.With improvement of swelling, the joint function improves and radius of action is enlarged and patients' physiological and psychological condition improves,so their general health improves.With treatment,each index is in the process of improvement.
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Effectively Improve Patients' DAS-28 Score and Lessen Arthritis Activity
DAS-28 is a comprehensive index to judge the RA activity in the international RA field and also an efficacy criterion to evaluate RA drug. This research takes DAS-28 to judge the efficacy of Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules in RA treatment.It is found that after 2 months,DAS-28 obviously improves and has statistical difference compared with that before treatment which fully proves that Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction is an effective medicine for RA.
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction Granules Lower Patients' HAQ Score and Improve Life Quality
Ramulus Cinnamomi,Paeoniae and Anemarrhenae Decoction can improve both the life quality and clinical syndrome consistently.After one month' s treatment,because of the improvement of joint haphalgesia and arthrocele, the patients' activity radius enlarges and they can finish some task which they couldn't do before.For example,with the improvement of upper extremity function and the shoulder and elbow function,the patients can put on clothes, bathe and wipe dry their bodies by themselves;with the improvement of wrist, finger and articulations interphalangeae patients can tie shoelace and buttons, take a glass of water to the mouth,and can open or close the tap or cork; with the improvement of coax and knee function,patients can get on or off bed by themselves and can walk on the outdoor ground,squat down,pick up the clothes on the floor,get on or off cars,etc.After two months' treatment, with the function improvement,there' s significant difference in deformity index compared with that before treatment.
With life ability improvement,patients feel they can relieve their families' burdens and are needed by others,so their mood improves and can gradually like what they are doing.They can lessen anxiety or dysphoria,calm down and lessen adverse moods like sadness or depression.By lessening discomfort of body,their psychological burden also lessens,so the HAQ Score improves with the recovery of physical syndromes.The current research shows that medical treatment can only inhibit the inflammation of RA but can' t repair the deformed joints and can' t reverse the lost function.So compared with clinical syndromes,the discomfort index takes longer time.Since part of the function can' t be repaired,the patients' discomfort is difficult to diminish.
Generalizing what we mention above,we find that Ramulus Cinnamomi, Paeoniae and Anemarrhenae Decoction can lessen arthrocele after one month' s treatment,obviously lessen the joint haphalgesia around two months and improve blood sedimentation around one month.It can improve patients' general evaluation of function and the DAS-28 score.Around two months' treatment,except discomfort index,each index is improved obviously around two months compared with those before treatment.After 3 months' treatment, all indexes are obviously improved.It shows that in analgesia,it takes effect slowly.But considering the other indexes,it is quicker in taking effect than Western Medicine.
引文
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[2]刘玉铱,范金茹.旭痹健步汤治疗类风湿关节炎的临床观察.湖南中医学院学报,1997,11(3):81
[3]周祖山,李拥.周承明对类风湿关节炎病机的独特认识及其意义.湖北中医杂志,2000,22(7):51
[4]罗小菊.中医辨治痹病的临床经验.辽宁中医学院学报,2000,1(2):371
[5]娄高峰.痹症与气血的关系探析.中医函授通讯,1999,18(4):231
[6]周学平,周仲英.中医药治疗类风湿关节炎的思路与方法.新中医,2001,33(1):51
[7]李文芳.王为兰论治类风湿关节炎.河南中医,1992,12(3):361
[8]门小平.旭痹三悟.中国医药学报,1993,8(5):471
[9]王宪庆,许金凤.从肝论治类风湿性关节炎.中医药学报,1999,(4):261
[10]张前德.类风湿关节炎的中医药治疗.南京中医药大学学报,2000,16(1):491
[11]李梢.类风湿关节炎从络辨治的理论体系初探.中医杂志,2002,43(2):85-881
[12]刘英.从毒探讨活动性类风湿关节炎的发病机制.山东中医杂志,2003,22(7):390-392
[13]董新民.类风湿关节炎的中医病因病机探讨.南京中医药大学学报,1996,12(4):91
[14]彭建中.赵绍琴教授从痰辨治类风湿关节炎的经验.中国中医药报,1994,9(5):571
[15]孙守华,马伟华.赵健雄教授辨治类风湿关节炎经验.甘肃中医,2001,14(3):141
[16]张虹.辨证治疗类风湿关节炎59例临床观察.山西中医,2001,17(4):231
[17]商宪敏,席宁.类风湿关节炎的中医证治.中国临床医生,2000,28(4):111
[18]吴敏玉.类风湿性关节炎发热66例辨证论治.北京中医,1992,2(2):251
[19]石昌平.加味桃红饮为主辨证治疗类风湿关节炎34例.陕西中医,1997,18(2):601
[20]王广元.以解毒通络法为主治疗类风湿关节炎.长春中医学院学报,1999,15(3):301
[21]路志正,焦树德.实用中医风湿病学.北京:人民卫生出版社,1996
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