金匮肾气丸颗粒治疗强直性脊柱炎的临床疗效研究
摘要
强直性脊柱炎(Ankylosing spondylitis,AS)是一种以累及脊柱和骶髂关节为特征的系统性炎性疾病,多见于青年男性患者,多数患者呈隐匿发病,病变早期呈转移性、上行性腰背疼痛,以下腰痛最多见,伴有困倦乏力、消瘦气短、贫血状,少数可伴有低热,以及晨僵、夜间翻身困难、起床费力或活动受限,一种姿势保持长久症状明显,此时常被忽视为腰肌劳损等其他疾病,常常不能引起人们的重视。本病发展缓慢,可迁延10-20年。发展到后期,病情发展往往较快,很短时间内形成驼背畸形,关节强直。
AS属中医“痹症”范畴,在中医古典医籍中有关“肾痹”、“骨痹”、“顽痹”、“历节风”、“腰痛”等的记载与现代之AS有颇多相似之处,这对后世探讨AS的病因病机及治疗提供了非常重要的指导意义。AS的发病机制尚不明确,目前尚无根治药物。近年来,中药治疗该病取得了较好疗效,且因毒副作用少而备受关注,并进行了深入研究。
我们认为,强直性脊柱炎的发病是内因与外因相互作用的结果。其内因为先天不足,后天失养,肝肾亏虚,督脉失养,阴阳气血失调,正气不固,但肾虚是发病的关键。外因为风寒湿热诸邪乘虚入侵,气血凝滞,筋骨不利以致拘挛痿弱不用。本病的初发部位多在腰骶部,100%的患者同时伴有骶髂关节炎。《素问·脉要精微论》:腰者肾之府。明确指出肾居腰之部位,腰,不但是实质的肾脏所在,还有足少阴、足太阳经脉与督脉循行,带脉的环绕,这些经脉都直接或间接的连属于肾。《圣济总录》云:腰者,一身之要,屈伸俯仰无不由之。因此肾虚不足所致之痹,或久痹及肾之证,都反映是腰府为病。腰以下为尻(现代医学的骶髂关节部位),宋·钱乙《小儿药证直诀》中明确指出“尻耳俱属于肾”,又,肾有二系,“一系下迫近骶尾,一系上脑髓”。说明了尻骨与肾的密切关系,而腰尻之痹是强直性脊柱炎区别于其他痹证的典型特征,这就决定了肾在强直性脊柱炎病因、病机中的主宰地位。金匮肾气丸来源于东汉末年张仲景所著《金匮要略》,是温补肾阳的代表方,也是最早的补肾方剂。本方补中有泻,寓泻于补,补不恋邪,泻不伤阴,相辅相成,实乃通补开合,标本兼治,协调阴阳之剂,故既能补不足,又能泻有余,既能通调,又能补合。肾气丸的这种组方配伍特点,正好是针对肾内藏真阴真阳为水火之脏的基本生理功能与特点而设,也切合强直性脊柱炎“肾精亏虚”的病机之本。
目前对金匮肾气丸治疗强直性脊柱炎的研究包括主要集中于临床和实验研究,临床研究多为简单的药物临床疗效观察,大多缺乏明确公认的诊断标准,疗效判断标准也可信度不高,实验研究多采用动物模型或人类细胞体外实验,距离临床实践较远,所以还不能充分说明金匮肾气丸治疗强直性脊柱炎的疗效。针对以上问题,我们设计了研究方案,选择严格的入选标准,国际公认的疗效判断标准。本研究的目的在于充分证明金匮肾气丸颗粒治疗强直性脊柱炎的疗效,为中医药治疗强直性脊柱炎提供充分证据。
1、方法
严格入组48例符合国际公认诊断标准、纳入标准、排除标准的强直性脊柱炎患者,用金匮肾气丸颗粒口服治疗,疗程6个月,采用国际公认ASAS20标准,分别于治疗前、治疗1个月后、治疗3个月后和治疗结束时BASDAI评分、BASFI评分、总体背痛和夜间悲痛评分、患者对病情的总体评价积分变化,并进行总体疗效评价,以期系统客观评价金匮肾气丸颗粒治疗强直性脊柱炎的临床疗效。
2、结果
2.1研究显示,治疗前,患者对BASDAI的评分较高,治疗后评分逐渐下降,其中治疗1月后BASDAI评分就比治疗前改善＞20%,和治疗前相比,有非常显著性差异,治疗3月后评分继续下降,治疗6月后评分亦较治疗3月时下降,但下降幅度逐渐减慢,BASDAI中最后两项有关晨僵内容VAS平均分变化和BASDAI评分变化一致,治疗一月后评分就与治疗前比较有非常显著差异,治疗3月和6月后评分逐步减少,治疗后改善达到20%。
2.2结果显示,治疗前,患者对BASFAI的评分较高,治疗后评分逐渐下降,其中治疗1月后BASFAI评分就比治疗前改善＞20%,与治疗前比较,差异有显著性;治疗3月后评分继续下降,与治疗前比较,差异非常显著;治疗6月后评分亦较治疗3月时下降,但下降幅度逐渐减慢,
2.3结果显示,治疗一个月后,患者总体背痛和夜间背痛都明显减轻,与治疗前比较,差异非常显著;治疗3个月和6个月后,各项评分继续下降;治疗结束时,总体背痛和夜间背痛的评分改善均达到20%。
2.4结果显示,治疗前患者对病情的总体评价评分较高,治疗一月后就有明显下降,差异非常显著,以后的治疗,评分进一步下降,治疗结束后评分下降超过20%。
2.5金匮肾气丸在治疗1个月时达到ASAS20的人数为26(54.17%),治疗6个月时达到ASAS20的人数为32(66.67%)。金匮肾气丸能有效减轻缓解期AS患者的临床症状,在治疗6个月后可明显改善AS患者的BASDAI、BASFI、患者对病情的总体评价、总体背痛、夜间背痛5项疗效指标,与治疗前比较有统计学差异,达到ASAS20标准。
3、结论
3.1金匮肾气丸颗粒明显改善强直性脊柱炎BASDAI评分
我们在研究中发现,强直性脊柱炎早期和活动程度强的时期,BASDAI评分较高,一般多见于青少年,身体素健,突然出现腰骶疼痛,有时痛的比较严重,有时上窜胸颈,有时下趋大腿足跟,甚至活动受限,生活不能自理。兼见郁怒烦躁,心烦起急,口干舌燥,便干溲赤,或有发热恶寒,或有低热,舌苔薄白或薄黄,脉象弦数。此时,扶正祛邪的治法中,要偏重祛邪,清热解毒、活血化瘀、利湿化浊等,而在疾病中晚期或活动程度弱的时期,BASDAI评分较低,患者出现腰膝酸软,活动不利,以及一派肝肾不足的虚象时,并不意味着疾病痊愈,而是说明邪气已不成为主要矛盾,而正虚则逐渐上升为主要矛盾,祛邪力度就要减轻,加强扶正。
BASDAI评价内容包括疲乏、中轴及外周关节疼痛、晨僵和肌腱端痛,共由6个问题组成,得分越高,病情越活动,一般大于4分提示病情活动。本研究发现,治疗前患者BASDAI平均得分约4分左右,提示本组强直性脊柱炎患者活动程度不高。部分患者处于疾病中晚期,部分处于相对静止期,在病机方面属于正虚为主者,故选用金匮肾气丸治疗切合病机,其中三补补肝肾,三泻通督脉,所以治疗一月后,BASDAI评分就出现明显下降,治疗三月后评分继续下降,至研究结束,评分一直下降,比治疗前明显好转。
3.2金匮肾气丸明显降低强直性脊柱炎患者BASFI评分
BASFI是Bath AS Function Index的简写。用来评价AS患者的综合功能状况。总得分越高,功能越差。在临床试验中,BASFI是用来评价药物治疗对患者功能改善程度的敏感指标。
强直性脊柱炎的基本病机是肾虚督滞,由于肝肾同源,肝主筋,肾主骨,肝肾不足,筋骨空虚,则转侧不利,活动不能,研究发现,患者治疗一个月后,BASFI有明显下降,说明患者功能明显改善,颈、腰、髋、膝功能好转,故评分下降,随着治疗的进行,肝肾空虚日渐得补,筋骨的功能逐渐恢复,故患者的日常功能活动更加改善,评分进一步下降,直到研究结束。
在研究过程中,我们发现,由于多数患者处于疾病活动缓解期,所以严重的腰骶关节疼痛不明显,而功能受限相对明显,由于病程长,肌腱韧带附着点的炎症造成脊柱功能受限,故药物治疗需要一个较长时期,我们治疗一个月后患者功能好转,3个月后好转更加明显,和BASDAI比较,BADFI下降速度相对较慢,3个月后与治疗前有非常显著差异,而BASDAI治疗一个月后就与治疗前出现非常显著差异。
我们还发现,三分吃药七分练是治疗强直性脊柱炎的基本法则,因为强直性脊柱炎是一种慢性的终身病,它是逐渐隐匿性发展的,它的发展是破坏脊柱的关节、韧带等,它使其僵硬、从炎症开始,炎症有发热、灼热破坏组织,阻滞一旦被破坏,待炎症缓解后,必生长新肉芽,把灵活的关节、韧带长在一起,失去活动能力,它就强直了,再想叫它恢复活动就难了。如果经常活动经常保持不固定,就长不到一起,炎症好了,活动关节仍能活动。另外活动也增加体力,关节不使其僵硬强直,体育运动是最好的方法。所以说体育运动,锻炼身体是最好的方法。
3.3金匮肾气丸颗粒明显改善强直性脊柱炎患者总体背痛和夜间背痛评分
《素问·上古天真论》云:女子七岁,肾气盛,齿更发长。二七而天癸至,任脉通,太冲脉盛,月事以时下,故有子。三七肾气平均,故真牙生而长极。四七筋骨坚,发长极,身体盛状。五七,阳明脉衰,面始焦,发始坠。六七,三阳脉衰于上,面皆焦,发始白。七七,任脉虚,太冲脉衰,天癸竭,地道不通,故形坏而无子也。丈夫八岁,肾气实,发长齿更。二八肾气盛,天癸至,精气溢泻,阴阳和,故有子。三八,肾气平均,筋骨劲强,故真牙生而长极。四八,筋骨隆盛,肌肉丰满。五八,肾气衰,发坠齿槁。六八,阳气衰竭于上,面焦,发鬓斑白。七八,肝气衰,筋不能动,天癸竭,精少,肾脏衰,形体皆极。八八则齿发去。肾者主水,受五脏六腑之精而藏之。故五脏盛,乃能泻。今五脏皆衰,筋骨解坠,天癸尽矣。这段经文突出反映了肾的精气在主持人体生长发育和生殖功能方面的作用,既是激发动力,又是物质基础。是肾之精气(肾阴、肾阳)的生理效应,齿、骨、发的生长状况是观察肾之精气盛衰的标志,综合了《素问·五藏生成篇》“肾之合骨也”、《宣明五气论》“肾主骨”、《阴阳应象大论》“肾生骨髓”、《解精微论》“髓者骨之充也”的一系列论点。肾藏精,主骨生髓,肾精的盛衰关系着骨的生长发育和骨的坚强脆弱。肾精充盛,骨髓充满则筋肌坚强,轻劲多力,肾为“作强之官,技巧则能出矣”。肾精不足,骨髓空疏,在强直性脊柱炎发病中有着重要的临床意义。
金匮肾气丸由干地黄八两,山药、山茱萸各四两,丹皮、茯苓、泽泻各三两,桂枝、炮附子各一两组成。方中滋阴药与助阳药并用,肾气、肾精并生,益肾之力足矣。故金匮肾气丸治疗后,患者肾精得养,腰背疼痛明显减轻,治疗前后好转达到20%标准。
3.4金匮肾气丸颗粒明显改善患者对病情的总体评价
脊柱的疼痛、活动受限严重影响患者的生存质量,本研究中患者虽然多数为强直性脊柱炎缓解期,但腰背的疼痛、功能的受限以及对治疗前景的不确定,使得患者对疾病的总体评价分较高,经金匮肾气丸治疗一月后,由于疼痛的减轻以及活动功能的改善,使得患者生存质量提高,故评分与治疗前相比改善非常显著,随着治疗的继续,评分进一步降低,达到20%改善标准。
3.5金匮肾气丸颗粒治疗强直性脊柱炎达到ASAS20标准
作为一种慢性病,AS需要有长期和短期的疗效评价。一年或以上为长期,一年以内为短期。ASAS工作组最早提出,需要从七个层面来评价AS的疗效,包括疾病控制抗风湿药的长期疗效,后来ASAS工作组经过研究,认为只需从四个层面来评价AS的疗效,即物理治疗、症状缓解抗风湿药、疾病控制抗风湿治疗和日常的临床记录。其定义是:(1)疾病控制抗风湿治疗必须能够从两方面改变AS的病程,通过减轻炎症反应而改善和维持关节功能;防止或明显地降低关节结构进行性损害的发生率,这些改变至少必须保持1年。(2)症状缓解抗风湿药必须能够改善AS的症状和炎症反应所致的临床特征。(3)日常临床记录的目的是促进保持统一的临床记录,以增强由临床记录所做的研究的强度。(4)对物理治疗的评价未作具体的规定。
1997年,ASAS工作组研究的第一步是从文献中寻找出110个可能与AS疗效评价有关的变量。根据上述定义,由36名参加的专家进行初选,有51个变量入选。再将参与研究的专家分为4个讨论组,以讨论组为单位,进行投票。结果,疾病控制抗风湿药的评价方面,物理功能、疼痛、脊柱活动度和外周关节与骨附着点分别得4分,脊柱的放射学改变和病人的综合评价分别得3分,髋关节放射学改变、脊柱僵硬、疲劳和急性期反应物分别得2分,医生的综合评价、社会经济结果、生命质量、药物安全性和骨骼外表现分别得1分。症状缓解抗风湿药的评价方面,疼痛、物理功能、脊柱僵硬和脊柱活动度分别得4分,病人的综合评价为3分,外周关节与骨附着点和医生的综合评价分别得1分。因此,该次讨论会的结果认为,对疾病控制抗风湿药的评价有6项必须包括的内容:物理功能、脊柱僵硬、脊柱活动度和病人的综合评价。根据上述研究所确定的10个因子,近几年来ASAS工作的专家门在着手于如何具体地评价各个因子的方法。目前初步确定的评价方法是:(1)物理功能,经过比较多个评价方法,初步确定采用巴氏AS功能指数或Dougados功能指数,两种方法均可选择;(2)疼痛,采用100mm目测标尺(VAS)估计近1周由于AS所致的夜间疼痛和由于AS所致的疼痛(不论昼夜);(3)脊柱活动度,包括胸廓活动度、Schober试验和枕-墙距;(4)脊柱僵硬:最近1周脊柱的晨僵时间;(5)病人总体评价,最近1周100mm VAS估计;(6)外周关节和骨附着点,从44个外周关节中计算肿胀关节数,骨附着点的评价尚未找到合适的方法;(7)急性时相反应物,虽然临床常用的急性时相反应物包括血沉和C反应蛋白,经ASAS工作组的讨论,认为血沉在临床上比C反应蛋白应用更广,所以最后只确定血沉代表急性时相反应物;(8)脊柱放射学改变,需要前后位和侧位的腰椎、侧位的颈椎和骨盆片,评价方法是采用巴氏AS放射学指数,还是Stoke的AS脊柱积分尚未确定;(9)髋关节照片,骨盆片可以包括髋关节,但是髋关节的评分方法还有待进一步确定;(10)疲劳。
后来ASAS工作组进一步精简提炼观察指标,提出了目前被国际风湿学界广泛采用的ASAS20,ASAS40等标准。本研究采用ASAS20标准,发现金匮肾气丸治疗强直性脊柱炎可达到ASAS20缓解标准,证实金匮肾气丸治疗的有效性。
Ankylosing spondylitis(AS) is a systematic inflammatory disease affecting spine column and articulatio sacroiliaca,commonly seen in young male patients.Most patients take the disease in delitescence.Early pathological changes are metastatic and upward lumbar and back pain with lower back pain most commonly seen.The other symptoms include fatigue and debility, emaciation and short breath,anemia,with a minority of patients accompanied by lower fever,early morning stiffness,difficulty in turning body over at night,difficulty in getting up and moving,etc.Keeping a posture for a long time causes obvious symptoms,which may easily ignored and classified as lumbar muscle strain.AS develops slowly and may extend to 10 to 20 years.It develops quickly at the late stage.Lump back and abnormity and arthrokleisis may form in a very short time.
AS is classified as arthromyodynia in Chinese Medicine.Renalarthralgia, rheumatism involving bone,obstinate arthralgia,severe and migratory arthralgia and lumbar pain recorded in Chinese Medicine classic works are much similar to AS in modern medicine,which provides important guidance for the research of AS etiological factors,pathogenesis and treatment.The pathogenesis of AS is not definite now and there' s no radically curative drugs. Recently,Chinese Medicine treatment of AS is given more attention and in-depth researches are undertaken as it achieves good curative efficacy and little toxic and side effects.
We believe AS is the result of interaction between the intrinsic factors and exopathic factors.The intrinsic factors include congenital deficiency, postnatal poor maintenance,liver and kidney deficiency,DU Meridian poor maintenance,disorder of yin,yang,qi and blood,healthy energy instability, however,kidney deficiency is the key factor.The exopathic factors include evasion of cold,dampness and heat evils,stagnation of qi and blood and disadvantage of bones and muscles,so tendon spasm,paralysis,weakness and disuse are caused.The initial disease part is mostly lumbosacral area with 100%of patients accompanied with sacroiliitis.Chapter 17 of Su Wen notes clearly that lumbar stores the kidney.Lumbar not only is where the substantial kidney lies,but also has foot-taiyin,foot-taiyang,Du Meridians and Belt Channel around,which directly or indirectly connect with and belong to kidney. General Collection for Holy Relief says lumbar is the key part of body and flexion,stretching,bending over and looking up all depend on lumbar. Therefore arthralgia spasm caused by kidney deficiency and kidney affected by long-time arthralgia spasm are all diseases of lumbar.Sacral region is below the lumbar which is called articulation sacroiliaca region in modern medicine.Qian Yi's Key to Therapeutics of Children's Disease in Song dynasty says clearly that sacral region and ear both belong to kidney and kidney has two belongings,one near sacral end,the other near brain and spine which explains clearly the close relationship between sacral region and kidney. Arthralgia spasm of lumbar and sacral region is the typical feature that differentiates AS from other arthromyodynia.This decides the controlling position of kidney in the etiology and pathogenesis of AS.Golden Chamber Kidney Qi Pill originates from Golden Chamber written by Zhang Zhongjing at the end of East Han Dynasty which is the representative prescription for warming and invigorating Kidney-yang and also the earliest prescription for invigorating kidney.In the prescription,there' s decanta in invigoration, and decanta doesn't hurt yin.Decanta and invigoration complement each other and cure both the root and syndromes of diseases.As a formula coordinating yin and yang,it reinforces the insufficiency and decanta the surplus.This formula takes into consideration the basic physiological features that kidney holds genuine yin and yang and is the viscera attributed to water and fire and is consistent with the pathogenesis of AS which is the deficiency of kidney-essence.
At present,researches on treatment of AS with Golden Chamber Kidney Qi Pill mainly focus on clinical and experimental researches.Clinical researches mainly adopt simple observations on drugs' clinical efficacy,most of which lack of clear and recognized diagnosis criteria and efficacy criteria credibility.Experimental researches mainly adopt animal model or human cell vitro researches which have certain distance away from the clinical practice and can' t fully prove the efficacy of Golden Chamber Kidney Qi Pill in AS treatment.Concerning these problems,we designed research plans,chose strict selection criteria and internationally recognized efficacy judgment criteria. The purpose of this research is to fully prove the efficacy of Golden Chamber Kidney Qi Pill in AS treatment and provide evidence for Chinese Medicine treatment of AS.
1.Methods
Strictly choose 48 AS patients consistent with the internationally recognized diagnostic,inclusion and exclusion criteria.Take Golden Chamber Kidney Qi Pill orally for 6 months.Grade on BASDAI,BASFI,general back pain, night back pain,patients' general evaluation of the disease and general efficacy according to internationally admitted ASAS20 criteria before the treatment,1 month after treatment,3 months after treatment and at the end of the treatment,so as to systematically and objectively evaluate the clinical efficacy of Golden Chamber Kidney Qi Pill on AS.
2.Results
2.1 Research shows patients' BASDAI grading is high before treatment and it drops gradually after treatment.1 month after treatment,the BASDAI grading improves at >20%compared with that before treatment and the difference is significant.The grading drops continuously after 3 months' treatment.The grading after 6 months' treatment is lower compared with that after 3 months' treatment,but the descending steps down gradually.About the last two items about morning stiffness in BASDAI grading,the VAS average change is consistent with BASDAI grading change.The grading 1 month after treatment has significant difference with that before treatment.The grading after 3 months' and 6 months' treatment gradually lessens and improves at 20%after treatment.
2.2 Research shows patients' BASFI grading is high before treatment and it drops gradually after treatment.1 month after treatment,the BASFI grading improves at >20%compared with that before treatment and the difference is significant.The grading drops continuously after 3 months' treatment.The difference is significant comparing it with that before treatment.The grading after 6 months' treatment is lower compared with that after 3 months' treatment,but the descending steps down gradually.
2.3 Research shows patients' general back pain and night back pain lessen after 1 month' s treatment.The difference is significant comparing them with those before treatment.The grading drops continuously after 3 months' and 6 months' treatment.At the end of the treatment,the general back pain and night back pain improve at 20%.
2.4 Research shows patients' general evaluation of disease is high before treatment and it drops after 1 month' s treatment.The difference is significant.The grading drops continuously in the later period of treatment and at the end of the treatment,the grading drops > 20%.
2.5 In the treatment with Golden Chamber Kidney Qi Pill,26 patients reached ASAS20 after 1 month' s treatment,32 patients after 6 months' treatment. Golden Chamber Kidney Qi Pill effectively lessens the AS patients' clinical symptoms in catabasis and can obviously improve the patients' BASDAI and BASFI grading,the general grading of diseases,the general back pain and night back pain grading.These reach ASAS20 criteria and have significant difference with those before treatment.
3.Conclusion
3.1 Golden Chamber Kidney Qi Pill Effectively Improves AS BASDAI Grading
In research,we find in the early stage and strong activity stage of AS, the BASDAI Grading is high.It occurs frequently in young people who are generally healthy but suddenly find lumbar and sacral pain.Sometimes it pains severely and sometimes it extends up to chest and neck and down to thigh and heel.Some even face limitation of activity and can' t take care of themselves. Some patients may be gloomy,agitated,upset and anxious.Some have dry mouth and tongue,dry stool,or fever with cold aversion,or low fever,thin and white lingual fur,thin and yellow lingual fur and frequent pulse tracings. We should emphasize eliminating pathogen,heat-clearing and detoxicating, promoting blood flow and eliminating bruise,eliminating dampness and turbidity.At the late stage and the weak activity stage of diseases,BASDAI grading is lower.The patients feel soft and feeble in lumbar and knee and it difficult to move.There' s false image of liver and kidney deficiency. It doesn' t mean that the disease is cured;however,it shows the pathogen qi is not the major contrary and asthenia qi deficiency gradually becomes the major contrary,so we need to lessen the intensity of pathogen elimination and reinforce the healthy qi.
BASDAI evaluation includes fatigue,central and peripheral joint pain, morning stiffness and tendon pain and consists of 6 questions.The higher the score,the more active the disease.If the score is >4,it indicates the disease proceeds.Research shows the BASDAI average before treatment is about 4 and indicates the AS patients' diseases in this group don' t proceed actively. Some patients at the middle or late stages have comparatively still stage of diseases.In pathogenesis,it' s mainly healthy qi deficiency,so Golden Chamber Kidney Qi Pill is adopted.The 3-inviogration invigorates liver and kidney and the 3-decanta smoothes Du Meridian.After 1 month' s treatment, the BASDAI grading obviously drops.After 3 months,it continuously drops until the end of the research.It is much better compared with that before treatment. 3.2 Golden Chamber Kidney Qi Pill Obviously Lowers the BASFI Grading of AS Patients
BASFI is short for Bath AS Function Index and used to evaluate the comprehensive function of AS patients.The higher the score,the poorer the function.In clinical trials,it' s a sensitivity index to evaluate the medical treatment on patients' function improvement.
The basic pathogen of AS is kidney deficiency and DU Meridian stagnation. Liver and kidney are from the same origin.Liver governs tendons and kidney governs bones.If there' s liver and kidney deficiency,the tendons and bones are deficient and have difficulty in moving.Research shows after one month' s treatment,the patients' BASFI obviously drops and shows the function improves obviously.The function of neck,lumbar,coax and knee function improves,so the grading drops.With treatment,the liver and kidney deficiency is gradually reinforced,the tendon and bone' s function gradually recovers, so the patients' daily activity improves and the grading drops until the end of the research.
In research,we find most patients are in eatabasis,so severe lumbar and sacral joint pain is not obvious,but the limitation of function is comparatively obvious.For the disease course is long and the inflammation of tendon ligament attachment point causes the limitation of spinal column function,so medical treatment takes a long time.After 1 month' s treatment, the function improves.After 3 months,the improvement is obvious.BASFI drops slowlier compared with BASDAI.The difference is significant 3 months after treatment compared with that before treatment;however the BASDAI difference is significant after just 1 month' s treatment.
We also find the basic principle for AS treatment is 30%of medicine and 70%of exercise.For AS is a chronic life-long disease,it develops delitescently and destroys spinal column joints and ligament.It starts with stiffening and inflammation.Inflammation destroys tissues with heat,after which the new granulation grows with flexible joints and ligaments,causing it to lose moving ability and difficult to recover.If the joints and ligament often moves,the granulation can' t grow together with them.After the inflammation,the joints can still move.Exercise can add strength and is the best way to keep joints from stiffness.
3.3 Golden Chamber Kidney Qi Pill Obviously Improves the General Back Pain and Night Back Pain Grading of AS Patients
The First Chapter of Su Wen says when a girl is 7 years old,the kidney qi is sufficient and teeth changes.At 14,kidney-essence for promoting reproductive function begins to take effect,Ren Meridian is smooth and Taichong Channel is sufficient.Regular menstrual cycle comes,so she can give birth.At 21,she has adequate kidney-qi,so the wisdom tooth grows and the body matures.At 28,she has strong tendon and bones,her hair grows to the extreme,and is very healthy.At 35,Yangming Meridian declines,the face turns yellowish and hair begins to drop.At 42,three yang meridians all decline, the face is all yellowish and hair turns white.At 49,the Ren Meridian is deficient,the Taichong Channel declines,the kidney-essence for reproductive ability exhausts and menostasis comes,so body wanes and she can' t give birth. When a boy is 8 years old,the kidney qi is sufficient,the hair grows and teeth changes.At 16,kidney-essence for promoting reproductive function begins to take effect,the kidney-qi is sufficient and spermatic ejaculation takes place.Children may be born if female and male have sexual intercourse. At 24,he has adequate kidney-qi and strong tendon and bones,so the wisdom tooth grows and the body matures.At 32,he has strongest tendon and bones as well as muscles.At 40,the kidney-qi declines,the hair drops and the teeth wither.At 48,the yang-qi declines,the face is all yellowish and hair turns white.At 56,the liver-qi is deficient,the tendons can' t move and the kidney-essence for reproductive ability exhausts,the essence is little, the kidney declines and the body wanes completely.At 64,the teeth all drop. The kidney governs water and stores the essence of five viscera and six Fu-organs.So if the five viscera are sufficient,the essence can be decanta. Now the five viscera all wanes,the tendons and bones are lazy and feeble, the reproductivity is gone.This paragraph stresses the function of kidney-qi in human growth and reproduction.It' s both the suscitation power and the material basis.The growth of teeth,bone and hair is the physiological effect of kidney-essence(kidney-yin and kidney-yang) and also reflects the sufficiency and deficiency of kidney-essence.It synthesizes a series of viewpoints,like the tissue connects with the kidney being bone from Chapter 10 of Su Wen,kidney governs the bones from Chapter 23 of Su Wen,kidney grows marrow from Chapter 5 of Su Wen and marrow fills the bones from Chapter 81 of Su Wen.Kidney stores essence,governs the growth of marrow and the sufficiency and deficiency of kidney-essence concerns the bones' growth and strength.Sufficient kidney-essence brings full marrow and strong tendons and muscles.If not,the marrow becomes hollow and weak.Therefore this is very important in clinical significance of AS.
Golden Chamber Kidney Qi Pill consists of adhesive rhemannia dried root 8 liang,batatatis and cornel 4 liang each,cortex moutan,hoelen and water plantation tuber 3 liang,ramulus cinnamomi and prepared commonot 1 liang each. Yin-increasing and yang-increasing medicine are both used in the formula,the kidney-qi and kidney-essence grow together,so the kidney reinforcement is enough.Therefore after treatment with Golden Chamber Kidney Qi Pill,the patient' s kidney-essence is nourished;the lumbar and back pain lessens obviously and improves at 20%.
3.4 Golden Chamber Kidney Qi Pill Obviously Improves Patients' General Evaluation of Diseases
Spinal column pain and activity limitation severely affects the life quality of patients.In this research,most patients are in AS catabasis,but the lumbar and back pain and limitation as well as the treatment prospect are not definite and clear,so the general evaluation of disease is high.After one month' s treatment with Golden Chamber Kidney Qi Pill,because of lessening pain and limitation of activity,the patients' life quality improves; therefore the grading improves significantly compared with that before treatment.With treatment going on,the grading further drops and reaches 20% improvement standard.
3.5 Golden Chamber Kidney-qi Pill Treatment of AS Reaches ASAS 20 Criteria As a chronic disease,AS demands long-term and short-term evaluation.One year or above is long term,and within 1 year is short term.ASAS team suggested originally that AS efficacy evaluation needs to be given from 7 decks, including disease controlling the anti-rheumatism drugs' long-term efficacy. After study,ASAS team believe it only needs 4 decks,namely the physical therapy,symptomatic relief anti-rheumatism drugs,disease controlling anti-rheumatism treatment and daily clinical record.The definition is:(1) disease controlling anti-rheumatism treatment changes AS disease course from 2 aspects,namely lessening inflammatory reaction to maintain and improve joint function and preventing or obviously lessens the occurrence rate of joint structure progressive injury which takes at least 1 year(2) symptomatic relief anti-rheumatism drugs must be able to improve AS symptoms and clinical features of inflammation(3) the purpose of daily clinical record is to keep the consistent clinical record and to strengthen the intensity of clinical record research(4) there' s no specific regulation about physical therapy
In 1997,ASAS team firstly selected 110 variables possibly related to AS efficacy evaluation from literature.According to the definition above,36 experts made preliminary selection and chose 51 variables.Experts were divided into 4 groups and vote.As a result in disease controlling the anti-rheumatism drugs,the physical function,pain,spinal column movement and peripheral joint and bone attachment point get 4 scores,spinal column' s radiological changes and patients' comprehensive grading get 3 scores,the coax joint radiological changes,spinal column stiffness,fatigue and acute phase reactant get 2 scores,the doctors' comprehensive evaluation,social and economical result,life quality,drug safety and skeleton outward appearance get 1 score.In symptomatic relief anti-rheumatism drug evaluation, pain,physical function,spinal column stiffness and movement get 4 scores, patients' comprehensive grading get 3 scores,peripheral joint and bone attachment and the doctors' comprehensive evaluation get 1 score.Therefore, that meeting' s result believed that disease controlling anti-rheumatism drug evaluation must include 6 contents:physical function,spinal column stiffness and movement and patients' comprehensive evaluation.10 factors are decided according to the research.In recent years,ASAS experts work on the specific ways to evaluate each factor.The preliminarily decided evaluation ways include:(1) physical function:adopts BASFI and Dougados Function Index and either is suitable to choose(2) pain:adopts VAS of 100 mm to evaluate night pain caused by AS and pain caused by AS(including day and night) in recent week(3) spinal column movement:including thorax movement,Schober test and pillow-wall distance(4) spinal column stiffness:the early morning stiffness time of spinal column in the recent week(5) patients' general evaluation: VAS of 100mm evaluation in recent week(6) peripheral joint and bone attachment point:count swollen joints from 44 peripheral joints;no suitable ways are found for the evaluation of bone attachment joints.(7) acute phase reactant: though acute phase reactant include blood sedimentation rate and C-reaction protein are frequently used clinically,the ASAS team believes,after discussion,that blood sedimentation rate applies in clinic more extensively than C-reaction protein,so blood sedimentation rate is finally decided as the acute phase reactant(8) spinal column radiological change:it needs the pieces of abdominal vertebra at A-P and lateral position and cervical vertebra and pelvis pieces at lateral position;whether to adopt Bath' s AS Radiological Index or Stoke' s AS Spinal Column INTGR is not decided.(9) coxa joint photograph:pelvis piece may include coax joint,but coax joint evaluation method needs to be decided(10) fatigue.
ASAS further simplifies the observation index and proposes ASAS 20 and ASAS 40 criteria recognized by international rheumatism study field.In this research,ASAS 20 criteria is adopted.It is found that Golden Chamber Kidney Qi Pill' s treatment of AS can reach ASAS 20 relief standard and it proves the efficacy of Golden Chamber Kidney Qi Pill.
AS属中医“痹症”范畴,在中医古典医籍中有关“肾痹”、“骨痹”、“顽痹”、“历节风”、“腰痛”等的记载与现代之AS有颇多相似之处,这对后世探讨AS的病因病机及治疗提供了非常重要的指导意义。AS的发病机制尚不明确,目前尚无根治药物。近年来,中药治疗该病取得了较好疗效,且因毒副作用少而备受关注,并进行了深入研究。
我们认为,强直性脊柱炎的发病是内因与外因相互作用的结果。其内因为先天不足,后天失养,肝肾亏虚,督脉失养,阴阳气血失调,正气不固,但肾虚是发病的关键。外因为风寒湿热诸邪乘虚入侵,气血凝滞,筋骨不利以致拘挛痿弱不用。本病的初发部位多在腰骶部,100%的患者同时伴有骶髂关节炎。《素问·脉要精微论》:腰者肾之府。明确指出肾居腰之部位,腰,不但是实质的肾脏所在,还有足少阴、足太阳经脉与督脉循行,带脉的环绕,这些经脉都直接或间接的连属于肾。《圣济总录》云:腰者,一身之要,屈伸俯仰无不由之。因此肾虚不足所致之痹,或久痹及肾之证,都反映是腰府为病。腰以下为尻(现代医学的骶髂关节部位),宋·钱乙《小儿药证直诀》中明确指出“尻耳俱属于肾”,又,肾有二系,“一系下迫近骶尾,一系上脑髓”。说明了尻骨与肾的密切关系,而腰尻之痹是强直性脊柱炎区别于其他痹证的典型特征,这就决定了肾在强直性脊柱炎病因、病机中的主宰地位。金匮肾气丸来源于东汉末年张仲景所著《金匮要略》,是温补肾阳的代表方,也是最早的补肾方剂。本方补中有泻,寓泻于补,补不恋邪,泻不伤阴,相辅相成,实乃通补开合,标本兼治,协调阴阳之剂,故既能补不足,又能泻有余,既能通调,又能补合。肾气丸的这种组方配伍特点,正好是针对肾内藏真阴真阳为水火之脏的基本生理功能与特点而设,也切合强直性脊柱炎“肾精亏虚”的病机之本。
目前对金匮肾气丸治疗强直性脊柱炎的研究包括主要集中于临床和实验研究,临床研究多为简单的药物临床疗效观察,大多缺乏明确公认的诊断标准,疗效判断标准也可信度不高,实验研究多采用动物模型或人类细胞体外实验,距离临床实践较远,所以还不能充分说明金匮肾气丸治疗强直性脊柱炎的疗效。针对以上问题,我们设计了研究方案,选择严格的入选标准,国际公认的疗效判断标准。本研究的目的在于充分证明金匮肾气丸颗粒治疗强直性脊柱炎的疗效,为中医药治疗强直性脊柱炎提供充分证据。
1、方法
严格入组48例符合国际公认诊断标准、纳入标准、排除标准的强直性脊柱炎患者,用金匮肾气丸颗粒口服治疗,疗程6个月,采用国际公认ASAS20标准,分别于治疗前、治疗1个月后、治疗3个月后和治疗结束时BASDAI评分、BASFI评分、总体背痛和夜间悲痛评分、患者对病情的总体评价积分变化,并进行总体疗效评价,以期系统客观评价金匮肾气丸颗粒治疗强直性脊柱炎的临床疗效。
2、结果
2.1研究显示,治疗前,患者对BASDAI的评分较高,治疗后评分逐渐下降,其中治疗1月后BASDAI评分就比治疗前改善＞20%,和治疗前相比,有非常显著性差异,治疗3月后评分继续下降,治疗6月后评分亦较治疗3月时下降,但下降幅度逐渐减慢,BASDAI中最后两项有关晨僵内容VAS平均分变化和BASDAI评分变化一致,治疗一月后评分就与治疗前比较有非常显著差异,治疗3月和6月后评分逐步减少,治疗后改善达到20%。
2.2结果显示,治疗前,患者对BASFAI的评分较高,治疗后评分逐渐下降,其中治疗1月后BASFAI评分就比治疗前改善＞20%,与治疗前比较,差异有显著性;治疗3月后评分继续下降,与治疗前比较,差异非常显著;治疗6月后评分亦较治疗3月时下降,但下降幅度逐渐减慢,
2.3结果显示,治疗一个月后,患者总体背痛和夜间背痛都明显减轻,与治疗前比较,差异非常显著;治疗3个月和6个月后,各项评分继续下降;治疗结束时,总体背痛和夜间背痛的评分改善均达到20%。
2.4结果显示,治疗前患者对病情的总体评价评分较高,治疗一月后就有明显下降,差异非常显著,以后的治疗,评分进一步下降,治疗结束后评分下降超过20%。
2.5金匮肾气丸在治疗1个月时达到ASAS20的人数为26(54.17%),治疗6个月时达到ASAS20的人数为32(66.67%)。金匮肾气丸能有效减轻缓解期AS患者的临床症状,在治疗6个月后可明显改善AS患者的BASDAI、BASFI、患者对病情的总体评价、总体背痛、夜间背痛5项疗效指标,与治疗前比较有统计学差异,达到ASAS20标准。
3、结论
3.1金匮肾气丸颗粒明显改善强直性脊柱炎BASDAI评分
我们在研究中发现,强直性脊柱炎早期和活动程度强的时期,BASDAI评分较高,一般多见于青少年,身体素健,突然出现腰骶疼痛,有时痛的比较严重,有时上窜胸颈,有时下趋大腿足跟,甚至活动受限,生活不能自理。兼见郁怒烦躁,心烦起急,口干舌燥,便干溲赤,或有发热恶寒,或有低热,舌苔薄白或薄黄,脉象弦数。此时,扶正祛邪的治法中,要偏重祛邪,清热解毒、活血化瘀、利湿化浊等,而在疾病中晚期或活动程度弱的时期,BASDAI评分较低,患者出现腰膝酸软,活动不利,以及一派肝肾不足的虚象时,并不意味着疾病痊愈,而是说明邪气已不成为主要矛盾,而正虚则逐渐上升为主要矛盾,祛邪力度就要减轻,加强扶正。
BASDAI评价内容包括疲乏、中轴及外周关节疼痛、晨僵和肌腱端痛,共由6个问题组成,得分越高,病情越活动,一般大于4分提示病情活动。本研究发现,治疗前患者BASDAI平均得分约4分左右,提示本组强直性脊柱炎患者活动程度不高。部分患者处于疾病中晚期,部分处于相对静止期,在病机方面属于正虚为主者,故选用金匮肾气丸治疗切合病机,其中三补补肝肾,三泻通督脉,所以治疗一月后,BASDAI评分就出现明显下降,治疗三月后评分继续下降,至研究结束,评分一直下降,比治疗前明显好转。
3.2金匮肾气丸明显降低强直性脊柱炎患者BASFI评分
BASFI是Bath AS Function Index的简写。用来评价AS患者的综合功能状况。总得分越高,功能越差。在临床试验中,BASFI是用来评价药物治疗对患者功能改善程度的敏感指标。
强直性脊柱炎的基本病机是肾虚督滞,由于肝肾同源,肝主筋,肾主骨,肝肾不足,筋骨空虚,则转侧不利,活动不能,研究发现,患者治疗一个月后,BASFI有明显下降,说明患者功能明显改善,颈、腰、髋、膝功能好转,故评分下降,随着治疗的进行,肝肾空虚日渐得补,筋骨的功能逐渐恢复,故患者的日常功能活动更加改善,评分进一步下降,直到研究结束。
在研究过程中,我们发现,由于多数患者处于疾病活动缓解期,所以严重的腰骶关节疼痛不明显,而功能受限相对明显,由于病程长,肌腱韧带附着点的炎症造成脊柱功能受限,故药物治疗需要一个较长时期,我们治疗一个月后患者功能好转,3个月后好转更加明显,和BASDAI比较,BADFI下降速度相对较慢,3个月后与治疗前有非常显著差异,而BASDAI治疗一个月后就与治疗前出现非常显著差异。
我们还发现,三分吃药七分练是治疗强直性脊柱炎的基本法则,因为强直性脊柱炎是一种慢性的终身病,它是逐渐隐匿性发展的,它的发展是破坏脊柱的关节、韧带等,它使其僵硬、从炎症开始,炎症有发热、灼热破坏组织,阻滞一旦被破坏,待炎症缓解后,必生长新肉芽,把灵活的关节、韧带长在一起,失去活动能力,它就强直了,再想叫它恢复活动就难了。如果经常活动经常保持不固定,就长不到一起,炎症好了,活动关节仍能活动。另外活动也增加体力,关节不使其僵硬强直,体育运动是最好的方法。所以说体育运动,锻炼身体是最好的方法。
3.3金匮肾气丸颗粒明显改善强直性脊柱炎患者总体背痛和夜间背痛评分
《素问·上古天真论》云:女子七岁,肾气盛,齿更发长。二七而天癸至,任脉通,太冲脉盛,月事以时下,故有子。三七肾气平均,故真牙生而长极。四七筋骨坚,发长极,身体盛状。五七,阳明脉衰,面始焦,发始坠。六七,三阳脉衰于上,面皆焦,发始白。七七,任脉虚,太冲脉衰,天癸竭,地道不通,故形坏而无子也。丈夫八岁,肾气实,发长齿更。二八肾气盛,天癸至,精气溢泻,阴阳和,故有子。三八,肾气平均,筋骨劲强,故真牙生而长极。四八,筋骨隆盛,肌肉丰满。五八,肾气衰,发坠齿槁。六八,阳气衰竭于上,面焦,发鬓斑白。七八,肝气衰,筋不能动,天癸竭,精少,肾脏衰,形体皆极。八八则齿发去。肾者主水,受五脏六腑之精而藏之。故五脏盛,乃能泻。今五脏皆衰,筋骨解坠,天癸尽矣。这段经文突出反映了肾的精气在主持人体生长发育和生殖功能方面的作用,既是激发动力,又是物质基础。是肾之精气(肾阴、肾阳)的生理效应,齿、骨、发的生长状况是观察肾之精气盛衰的标志,综合了《素问·五藏生成篇》“肾之合骨也”、《宣明五气论》“肾主骨”、《阴阳应象大论》“肾生骨髓”、《解精微论》“髓者骨之充也”的一系列论点。肾藏精,主骨生髓,肾精的盛衰关系着骨的生长发育和骨的坚强脆弱。肾精充盛,骨髓充满则筋肌坚强,轻劲多力,肾为“作强之官,技巧则能出矣”。肾精不足,骨髓空疏,在强直性脊柱炎发病中有着重要的临床意义。
金匮肾气丸由干地黄八两,山药、山茱萸各四两,丹皮、茯苓、泽泻各三两,桂枝、炮附子各一两组成。方中滋阴药与助阳药并用,肾气、肾精并生,益肾之力足矣。故金匮肾气丸治疗后,患者肾精得养,腰背疼痛明显减轻,治疗前后好转达到20%标准。
3.4金匮肾气丸颗粒明显改善患者对病情的总体评价
脊柱的疼痛、活动受限严重影响患者的生存质量,本研究中患者虽然多数为强直性脊柱炎缓解期,但腰背的疼痛、功能的受限以及对治疗前景的不确定,使得患者对疾病的总体评价分较高,经金匮肾气丸治疗一月后,由于疼痛的减轻以及活动功能的改善,使得患者生存质量提高,故评分与治疗前相比改善非常显著,随着治疗的继续,评分进一步降低,达到20%改善标准。
3.5金匮肾气丸颗粒治疗强直性脊柱炎达到ASAS20标准
作为一种慢性病,AS需要有长期和短期的疗效评价。一年或以上为长期,一年以内为短期。ASAS工作组最早提出,需要从七个层面来评价AS的疗效,包括疾病控制抗风湿药的长期疗效,后来ASAS工作组经过研究,认为只需从四个层面来评价AS的疗效,即物理治疗、症状缓解抗风湿药、疾病控制抗风湿治疗和日常的临床记录。其定义是:(1)疾病控制抗风湿治疗必须能够从两方面改变AS的病程,通过减轻炎症反应而改善和维持关节功能;防止或明显地降低关节结构进行性损害的发生率,这些改变至少必须保持1年。(2)症状缓解抗风湿药必须能够改善AS的症状和炎症反应所致的临床特征。(3)日常临床记录的目的是促进保持统一的临床记录,以增强由临床记录所做的研究的强度。(4)对物理治疗的评价未作具体的规定。
1997年,ASAS工作组研究的第一步是从文献中寻找出110个可能与AS疗效评价有关的变量。根据上述定义,由36名参加的专家进行初选,有51个变量入选。再将参与研究的专家分为4个讨论组,以讨论组为单位,进行投票。结果,疾病控制抗风湿药的评价方面,物理功能、疼痛、脊柱活动度和外周关节与骨附着点分别得4分,脊柱的放射学改变和病人的综合评价分别得3分,髋关节放射学改变、脊柱僵硬、疲劳和急性期反应物分别得2分,医生的综合评价、社会经济结果、生命质量、药物安全性和骨骼外表现分别得1分。症状缓解抗风湿药的评价方面,疼痛、物理功能、脊柱僵硬和脊柱活动度分别得4分,病人的综合评价为3分,外周关节与骨附着点和医生的综合评价分别得1分。因此,该次讨论会的结果认为,对疾病控制抗风湿药的评价有6项必须包括的内容:物理功能、脊柱僵硬、脊柱活动度和病人的综合评价。根据上述研究所确定的10个因子,近几年来ASAS工作的专家门在着手于如何具体地评价各个因子的方法。目前初步确定的评价方法是:(1)物理功能,经过比较多个评价方法,初步确定采用巴氏AS功能指数或Dougados功能指数,两种方法均可选择;(2)疼痛,采用100mm目测标尺(VAS)估计近1周由于AS所致的夜间疼痛和由于AS所致的疼痛(不论昼夜);(3)脊柱活动度,包括胸廓活动度、Schober试验和枕-墙距;(4)脊柱僵硬:最近1周脊柱的晨僵时间;(5)病人总体评价,最近1周100mm VAS估计;(6)外周关节和骨附着点,从44个外周关节中计算肿胀关节数,骨附着点的评价尚未找到合适的方法;(7)急性时相反应物,虽然临床常用的急性时相反应物包括血沉和C反应蛋白,经ASAS工作组的讨论,认为血沉在临床上比C反应蛋白应用更广,所以最后只确定血沉代表急性时相反应物;(8)脊柱放射学改变,需要前后位和侧位的腰椎、侧位的颈椎和骨盆片,评价方法是采用巴氏AS放射学指数,还是Stoke的AS脊柱积分尚未确定;(9)髋关节照片,骨盆片可以包括髋关节,但是髋关节的评分方法还有待进一步确定;(10)疲劳。
后来ASAS工作组进一步精简提炼观察指标,提出了目前被国际风湿学界广泛采用的ASAS20,ASAS40等标准。本研究采用ASAS20标准,发现金匮肾气丸治疗强直性脊柱炎可达到ASAS20缓解标准,证实金匮肾气丸治疗的有效性。
Ankylosing spondylitis(AS) is a systematic inflammatory disease affecting spine column and articulatio sacroiliaca,commonly seen in young male patients.Most patients take the disease in delitescence.Early pathological changes are metastatic and upward lumbar and back pain with lower back pain most commonly seen.The other symptoms include fatigue and debility, emaciation and short breath,anemia,with a minority of patients accompanied by lower fever,early morning stiffness,difficulty in turning body over at night,difficulty in getting up and moving,etc.Keeping a posture for a long time causes obvious symptoms,which may easily ignored and classified as lumbar muscle strain.AS develops slowly and may extend to 10 to 20 years.It develops quickly at the late stage.Lump back and abnormity and arthrokleisis may form in a very short time.
AS is classified as arthromyodynia in Chinese Medicine.Renalarthralgia, rheumatism involving bone,obstinate arthralgia,severe and migratory arthralgia and lumbar pain recorded in Chinese Medicine classic works are much similar to AS in modern medicine,which provides important guidance for the research of AS etiological factors,pathogenesis and treatment.The pathogenesis of AS is not definite now and there' s no radically curative drugs. Recently,Chinese Medicine treatment of AS is given more attention and in-depth researches are undertaken as it achieves good curative efficacy and little toxic and side effects.
We believe AS is the result of interaction between the intrinsic factors and exopathic factors.The intrinsic factors include congenital deficiency, postnatal poor maintenance,liver and kidney deficiency,DU Meridian poor maintenance,disorder of yin,yang,qi and blood,healthy energy instability, however,kidney deficiency is the key factor.The exopathic factors include evasion of cold,dampness and heat evils,stagnation of qi and blood and disadvantage of bones and muscles,so tendon spasm,paralysis,weakness and disuse are caused.The initial disease part is mostly lumbosacral area with 100%of patients accompanied with sacroiliitis.Chapter 17 of Su Wen notes clearly that lumbar stores the kidney.Lumbar not only is where the substantial kidney lies,but also has foot-taiyin,foot-taiyang,Du Meridians and Belt Channel around,which directly or indirectly connect with and belong to kidney. General Collection for Holy Relief says lumbar is the key part of body and flexion,stretching,bending over and looking up all depend on lumbar. Therefore arthralgia spasm caused by kidney deficiency and kidney affected by long-time arthralgia spasm are all diseases of lumbar.Sacral region is below the lumbar which is called articulation sacroiliaca region in modern medicine.Qian Yi's Key to Therapeutics of Children's Disease in Song dynasty says clearly that sacral region and ear both belong to kidney and kidney has two belongings,one near sacral end,the other near brain and spine which explains clearly the close relationship between sacral region and kidney. Arthralgia spasm of lumbar and sacral region is the typical feature that differentiates AS from other arthromyodynia.This decides the controlling position of kidney in the etiology and pathogenesis of AS.Golden Chamber Kidney Qi Pill originates from Golden Chamber written by Zhang Zhongjing at the end of East Han Dynasty which is the representative prescription for warming and invigorating Kidney-yang and also the earliest prescription for invigorating kidney.In the prescription,there' s decanta in invigoration, and decanta doesn't hurt yin.Decanta and invigoration complement each other and cure both the root and syndromes of diseases.As a formula coordinating yin and yang,it reinforces the insufficiency and decanta the surplus.This formula takes into consideration the basic physiological features that kidney holds genuine yin and yang and is the viscera attributed to water and fire and is consistent with the pathogenesis of AS which is the deficiency of kidney-essence.
At present,researches on treatment of AS with Golden Chamber Kidney Qi Pill mainly focus on clinical and experimental researches.Clinical researches mainly adopt simple observations on drugs' clinical efficacy,most of which lack of clear and recognized diagnosis criteria and efficacy criteria credibility.Experimental researches mainly adopt animal model or human cell vitro researches which have certain distance away from the clinical practice and can' t fully prove the efficacy of Golden Chamber Kidney Qi Pill in AS treatment.Concerning these problems,we designed research plans,chose strict selection criteria and internationally recognized efficacy judgment criteria. The purpose of this research is to fully prove the efficacy of Golden Chamber Kidney Qi Pill in AS treatment and provide evidence for Chinese Medicine treatment of AS.
1.Methods
Strictly choose 48 AS patients consistent with the internationally recognized diagnostic,inclusion and exclusion criteria.Take Golden Chamber Kidney Qi Pill orally for 6 months.Grade on BASDAI,BASFI,general back pain, night back pain,patients' general evaluation of the disease and general efficacy according to internationally admitted ASAS20 criteria before the treatment,1 month after treatment,3 months after treatment and at the end of the treatment,so as to systematically and objectively evaluate the clinical efficacy of Golden Chamber Kidney Qi Pill on AS.
2.Results
2.1 Research shows patients' BASDAI grading is high before treatment and it drops gradually after treatment.1 month after treatment,the BASDAI grading improves at >20%compared with that before treatment and the difference is significant.The grading drops continuously after 3 months' treatment.The grading after 6 months' treatment is lower compared with that after 3 months' treatment,but the descending steps down gradually.About the last two items about morning stiffness in BASDAI grading,the VAS average change is consistent with BASDAI grading change.The grading 1 month after treatment has significant difference with that before treatment.The grading after 3 months' and 6 months' treatment gradually lessens and improves at 20%after treatment.
2.2 Research shows patients' BASFI grading is high before treatment and it drops gradually after treatment.1 month after treatment,the BASFI grading improves at >20%compared with that before treatment and the difference is significant.The grading drops continuously after 3 months' treatment.The difference is significant comparing it with that before treatment.The grading after 6 months' treatment is lower compared with that after 3 months' treatment,but the descending steps down gradually.
2.3 Research shows patients' general back pain and night back pain lessen after 1 month' s treatment.The difference is significant comparing them with those before treatment.The grading drops continuously after 3 months' and 6 months' treatment.At the end of the treatment,the general back pain and night back pain improve at 20%.
2.4 Research shows patients' general evaluation of disease is high before treatment and it drops after 1 month' s treatment.The difference is significant.The grading drops continuously in the later period of treatment and at the end of the treatment,the grading drops > 20%.
2.5 In the treatment with Golden Chamber Kidney Qi Pill,26 patients reached ASAS20 after 1 month' s treatment,32 patients after 6 months' treatment. Golden Chamber Kidney Qi Pill effectively lessens the AS patients' clinical symptoms in catabasis and can obviously improve the patients' BASDAI and BASFI grading,the general grading of diseases,the general back pain and night back pain grading.These reach ASAS20 criteria and have significant difference with those before treatment.
3.Conclusion
3.1 Golden Chamber Kidney Qi Pill Effectively Improves AS BASDAI Grading
In research,we find in the early stage and strong activity stage of AS, the BASDAI Grading is high.It occurs frequently in young people who are generally healthy but suddenly find lumbar and sacral pain.Sometimes it pains severely and sometimes it extends up to chest and neck and down to thigh and heel.Some even face limitation of activity and can' t take care of themselves. Some patients may be gloomy,agitated,upset and anxious.Some have dry mouth and tongue,dry stool,or fever with cold aversion,or low fever,thin and white lingual fur,thin and yellow lingual fur and frequent pulse tracings. We should emphasize eliminating pathogen,heat-clearing and detoxicating, promoting blood flow and eliminating bruise,eliminating dampness and turbidity.At the late stage and the weak activity stage of diseases,BASDAI grading is lower.The patients feel soft and feeble in lumbar and knee and it difficult to move.There' s false image of liver and kidney deficiency. It doesn' t mean that the disease is cured;however,it shows the pathogen qi is not the major contrary and asthenia qi deficiency gradually becomes the major contrary,so we need to lessen the intensity of pathogen elimination and reinforce the healthy qi.
BASDAI evaluation includes fatigue,central and peripheral joint pain, morning stiffness and tendon pain and consists of 6 questions.The higher the score,the more active the disease.If the score is >4,it indicates the disease proceeds.Research shows the BASDAI average before treatment is about 4 and indicates the AS patients' diseases in this group don' t proceed actively. Some patients at the middle or late stages have comparatively still stage of diseases.In pathogenesis,it' s mainly healthy qi deficiency,so Golden Chamber Kidney Qi Pill is adopted.The 3-inviogration invigorates liver and kidney and the 3-decanta smoothes Du Meridian.After 1 month' s treatment, the BASDAI grading obviously drops.After 3 months,it continuously drops until the end of the research.It is much better compared with that before treatment. 3.2 Golden Chamber Kidney Qi Pill Obviously Lowers the BASFI Grading of AS Patients
BASFI is short for Bath AS Function Index and used to evaluate the comprehensive function of AS patients.The higher the score,the poorer the function.In clinical trials,it' s a sensitivity index to evaluate the medical treatment on patients' function improvement.
The basic pathogen of AS is kidney deficiency and DU Meridian stagnation. Liver and kidney are from the same origin.Liver governs tendons and kidney governs bones.If there' s liver and kidney deficiency,the tendons and bones are deficient and have difficulty in moving.Research shows after one month' s treatment,the patients' BASFI obviously drops and shows the function improves obviously.The function of neck,lumbar,coax and knee function improves,so the grading drops.With treatment,the liver and kidney deficiency is gradually reinforced,the tendon and bone' s function gradually recovers, so the patients' daily activity improves and the grading drops until the end of the research.
In research,we find most patients are in eatabasis,so severe lumbar and sacral joint pain is not obvious,but the limitation of function is comparatively obvious.For the disease course is long and the inflammation of tendon ligament attachment point causes the limitation of spinal column function,so medical treatment takes a long time.After 1 month' s treatment, the function improves.After 3 months,the improvement is obvious.BASFI drops slowlier compared with BASDAI.The difference is significant 3 months after treatment compared with that before treatment;however the BASDAI difference is significant after just 1 month' s treatment.
We also find the basic principle for AS treatment is 30%of medicine and 70%of exercise.For AS is a chronic life-long disease,it develops delitescently and destroys spinal column joints and ligament.It starts with stiffening and inflammation.Inflammation destroys tissues with heat,after which the new granulation grows with flexible joints and ligaments,causing it to lose moving ability and difficult to recover.If the joints and ligament often moves,the granulation can' t grow together with them.After the inflammation,the joints can still move.Exercise can add strength and is the best way to keep joints from stiffness.
3.3 Golden Chamber Kidney Qi Pill Obviously Improves the General Back Pain and Night Back Pain Grading of AS Patients
The First Chapter of Su Wen says when a girl is 7 years old,the kidney qi is sufficient and teeth changes.At 14,kidney-essence for promoting reproductive function begins to take effect,Ren Meridian is smooth and Taichong Channel is sufficient.Regular menstrual cycle comes,so she can give birth.At 21,she has adequate kidney-qi,so the wisdom tooth grows and the body matures.At 28,she has strong tendon and bones,her hair grows to the extreme,and is very healthy.At 35,Yangming Meridian declines,the face turns yellowish and hair begins to drop.At 42,three yang meridians all decline, the face is all yellowish and hair turns white.At 49,the Ren Meridian is deficient,the Taichong Channel declines,the kidney-essence for reproductive ability exhausts and menostasis comes,so body wanes and she can' t give birth. When a boy is 8 years old,the kidney qi is sufficient,the hair grows and teeth changes.At 16,kidney-essence for promoting reproductive function begins to take effect,the kidney-qi is sufficient and spermatic ejaculation takes place.Children may be born if female and male have sexual intercourse. At 24,he has adequate kidney-qi and strong tendon and bones,so the wisdom tooth grows and the body matures.At 32,he has strongest tendon and bones as well as muscles.At 40,the kidney-qi declines,the hair drops and the teeth wither.At 48,the yang-qi declines,the face is all yellowish and hair turns white.At 56,the liver-qi is deficient,the tendons can' t move and the kidney-essence for reproductive ability exhausts,the essence is little, the kidney declines and the body wanes completely.At 64,the teeth all drop. The kidney governs water and stores the essence of five viscera and six Fu-organs.So if the five viscera are sufficient,the essence can be decanta. Now the five viscera all wanes,the tendons and bones are lazy and feeble, the reproductivity is gone.This paragraph stresses the function of kidney-qi in human growth and reproduction.It' s both the suscitation power and the material basis.The growth of teeth,bone and hair is the physiological effect of kidney-essence(kidney-yin and kidney-yang) and also reflects the sufficiency and deficiency of kidney-essence.It synthesizes a series of viewpoints,like the tissue connects with the kidney being bone from Chapter 10 of Su Wen,kidney governs the bones from Chapter 23 of Su Wen,kidney grows marrow from Chapter 5 of Su Wen and marrow fills the bones from Chapter 81 of Su Wen.Kidney stores essence,governs the growth of marrow and the sufficiency and deficiency of kidney-essence concerns the bones' growth and strength.Sufficient kidney-essence brings full marrow and strong tendons and muscles.If not,the marrow becomes hollow and weak.Therefore this is very important in clinical significance of AS.
Golden Chamber Kidney Qi Pill consists of adhesive rhemannia dried root 8 liang,batatatis and cornel 4 liang each,cortex moutan,hoelen and water plantation tuber 3 liang,ramulus cinnamomi and prepared commonot 1 liang each. Yin-increasing and yang-increasing medicine are both used in the formula,the kidney-qi and kidney-essence grow together,so the kidney reinforcement is enough.Therefore after treatment with Golden Chamber Kidney Qi Pill,the patient' s kidney-essence is nourished;the lumbar and back pain lessens obviously and improves at 20%.
3.4 Golden Chamber Kidney Qi Pill Obviously Improves Patients' General Evaluation of Diseases
Spinal column pain and activity limitation severely affects the life quality of patients.In this research,most patients are in AS catabasis,but the lumbar and back pain and limitation as well as the treatment prospect are not definite and clear,so the general evaluation of disease is high.After one month' s treatment with Golden Chamber Kidney Qi Pill,because of lessening pain and limitation of activity,the patients' life quality improves; therefore the grading improves significantly compared with that before treatment.With treatment going on,the grading further drops and reaches 20% improvement standard.
3.5 Golden Chamber Kidney-qi Pill Treatment of AS Reaches ASAS 20 Criteria As a chronic disease,AS demands long-term and short-term evaluation.One year or above is long term,and within 1 year is short term.ASAS team suggested originally that AS efficacy evaluation needs to be given from 7 decks, including disease controlling the anti-rheumatism drugs' long-term efficacy. After study,ASAS team believe it only needs 4 decks,namely the physical therapy,symptomatic relief anti-rheumatism drugs,disease controlling anti-rheumatism treatment and daily clinical record.The definition is:(1) disease controlling anti-rheumatism treatment changes AS disease course from 2 aspects,namely lessening inflammatory reaction to maintain and improve joint function and preventing or obviously lessens the occurrence rate of joint structure progressive injury which takes at least 1 year(2) symptomatic relief anti-rheumatism drugs must be able to improve AS symptoms and clinical features of inflammation(3) the purpose of daily clinical record is to keep the consistent clinical record and to strengthen the intensity of clinical record research(4) there' s no specific regulation about physical therapy
In 1997,ASAS team firstly selected 110 variables possibly related to AS efficacy evaluation from literature.According to the definition above,36 experts made preliminary selection and chose 51 variables.Experts were divided into 4 groups and vote.As a result in disease controlling the anti-rheumatism drugs,the physical function,pain,spinal column movement and peripheral joint and bone attachment point get 4 scores,spinal column' s radiological changes and patients' comprehensive grading get 3 scores,the coax joint radiological changes,spinal column stiffness,fatigue and acute phase reactant get 2 scores,the doctors' comprehensive evaluation,social and economical result,life quality,drug safety and skeleton outward appearance get 1 score.In symptomatic relief anti-rheumatism drug evaluation, pain,physical function,spinal column stiffness and movement get 4 scores, patients' comprehensive grading get 3 scores,peripheral joint and bone attachment and the doctors' comprehensive evaluation get 1 score.Therefore, that meeting' s result believed that disease controlling anti-rheumatism drug evaluation must include 6 contents:physical function,spinal column stiffness and movement and patients' comprehensive evaluation.10 factors are decided according to the research.In recent years,ASAS experts work on the specific ways to evaluate each factor.The preliminarily decided evaluation ways include:(1) physical function:adopts BASFI and Dougados Function Index and either is suitable to choose(2) pain:adopts VAS of 100 mm to evaluate night pain caused by AS and pain caused by AS(including day and night) in recent week(3) spinal column movement:including thorax movement,Schober test and pillow-wall distance(4) spinal column stiffness:the early morning stiffness time of spinal column in the recent week(5) patients' general evaluation: VAS of 100mm evaluation in recent week(6) peripheral joint and bone attachment point:count swollen joints from 44 peripheral joints;no suitable ways are found for the evaluation of bone attachment joints.(7) acute phase reactant: though acute phase reactant include blood sedimentation rate and C-reaction protein are frequently used clinically,the ASAS team believes,after discussion,that blood sedimentation rate applies in clinic more extensively than C-reaction protein,so blood sedimentation rate is finally decided as the acute phase reactant(8) spinal column radiological change:it needs the pieces of abdominal vertebra at A-P and lateral position and cervical vertebra and pelvis pieces at lateral position;whether to adopt Bath' s AS Radiological Index or Stoke' s AS Spinal Column INTGR is not decided.(9) coxa joint photograph:pelvis piece may include coax joint,but coax joint evaluation method needs to be decided(10) fatigue.
ASAS further simplifies the observation index and proposes ASAS 20 and ASAS 40 criteria recognized by international rheumatism study field.In this research,ASAS 20 criteria is adopted.It is found that Golden Chamber Kidney Qi Pill' s treatment of AS can reach ASAS 20 relief standard and it proves the efficacy of Golden Chamber Kidney Qi Pill.
引文
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