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吉海旺教授治疗类风湿性关节炎的学术经验研究
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摘要
类风湿性关节炎(Rheumatoid Arthritis, RA)是一种以对称性多关节炎为主要临床表现的自身免疫性疾病。该病以关节滑膜慢性炎症、关节的进行性破坏为特征,临床表现变化多端,预后往往较差,晚期可引起关节强直、畸形和功能严重受损,同时可造成心、肺、’肾等多脏器、多系统损害,严重危害患者的健康和生存质量。RA在世界各地均有发病,我国北方地区为本病的高发区。因此,RA的防治具有重要的理论与社会意义。
     中医学中并没有类风湿性关节炎这一病名,多归属于“痹证”范畴。因该病病情顽固、缠绵难愈、临床表现多样,并可造成多脏器、多系统损害,故又将其称为“顽痹”、“骨痹”、“肾痹”、“风湿”、“历节”、“鹤膝风”、“鼓槌风”等,现代中医多以焦树德教授确立的“旭痹”为其诊断名称。
     吉海旺教授,主任医师,博士生导师,从医30余载,致力于中医内科疾病的诊治与研究,治杂病推崇脏腑辨证,从脏腑入手,驾简驭繁。提出从脾论治咳嗽、从肝论治痞满、从脾肾论治痛风、从脾胃论治难治性口腔溃疡、从肝脾肾论治脱发等脏腑辨证论治的学术思想。
     在风湿病的研究领域中,吉海旺教授进行了深入研究,积累了丰富的临床经验,建树颇多。认为类风湿性关节炎具有起病较缓、病程长、缠绵难愈的特点,肾虚是发病的基础,外邪侵入是发病的重要条件,瘀血阻络为其病理基础。这里所说的“外邪”只是一个广义的概念,包含寒冷、潮湿等不良环境因素以及现代医学所说的细菌、病毒等因素。肾虚既包括先天禀赋的缺陷,也包括免疫功能的紊乱。提出治疗类风湿性关节炎以肾为主,补肾填精以益先天、补肾健脾以养后天、补肾滋肝养阴柔筋、补肾养血充实营卫、补肾温阳活血通络的学术思想。
     根据类风湿性关节炎的发病过程,吉海旺教授将其分为急性期、亚急性期及慢性期三期。本着急则治其标、缓则治其本的原则,在急性期多证属湿热伤肾,治以清热祛风,补肾活血;亚急性期多证属肾虚寒侵,治以祛风除湿,补肾活血;慢性期多证属肾虚血瘀,治以补肾活血,通络止痛。做到祛邪不伤正,扶正不留邪,补肾贯穿始终。用药特点为在类风湿性关节炎的急性期,所用药物以祛风清热为主,随着病情的进展,补肾药与活血药比例逐渐增大,与类风湿性关节炎以肾为主分期论治的治疗思想相符合。
     本研究通过回顾性及前瞻性的临床研究,初步探讨吉海旺教授补肾为主治疗类风湿性关节炎的辨治规律。通过选用吉海旺教授研制的风湿Ⅱ号胶囊治疗类风湿性关节炎肾虚血瘀证,证实补肾活血为主治疗类风湿性关节炎的有效性及安全性。
     通过将吉海旺教授诊治的类风湿性关节炎患者病历(门诊及住院病历)70例,共209诊次,进行回顾性研究,记录相关临床症状、体征及药物使用情况,并对数据进行统计分析。研究发现RA最常见症状依次为:关节疼痛占18.03%,晨僵占10.03%,关节肿胀占8.49%,关节屈伸不利占8.39%;其次所占比例较大的为腰膝酸软、神疲乏力、面色无华、关节畸形、面色晄白、肢冷不温,疼痛遇寒加重,恶风寒,皮色暗红,疼痛夜甚等症状。从舌脉而言,研究发现舌质淡占71.60%;苔薄白占86.43%;细脉占总脉象的34.85%,沉脉为7.20%,沉细脉为19.32%,共占61.37%。从证候分布而言,肾虚血瘀证占50.00%,肾虚寒侵证占33.86%,湿热伤肾证占7.14%,其他证候共占10.00%。从治疗药物而言,祛风湿药所占比例最大,为28.46%;其次为补肾药,占23.07%;再次为活血药,占21.25%;解表药紧随其后,占10.97%,体现出吉海旺教授补肾活血,兼以祛风除湿的用药规律。
     选择符合类风湿性关节炎肾虚血瘀证纳入标准的患者60例,分为治疗组和对照组,治疗组给予风湿11号胶囊,4粒/次,1日3次;对照组给予甲氨蝶呤片,7.5mg/次,每周1次。疗程均为12周,观察补肾活血法(风湿Ⅱ号胶囊)治疗类风湿性关节炎的有效性及安全性。结果表明:在疾病疗效方面,风湿Ⅱ号胶囊总有效率为96.67%,与甲氨蝶呤相比,差异有统计学意义(P<0.01),提示风湿Ⅱ号胶囊对类风湿性关节炎的疗效优于甲氨蝶呤。进一步比较两组主要指标疗效,发现无论甲氨蝶呤还是风湿Ⅱ号胶囊,在改善类风湿性关节炎的疼痛、关节压痛数、关节肿胀数、晨僵时间及平均握力上,均有显著疗效(P<0.01)。风湿Ⅱ号胶囊在缓解疼痛及关节肿胀上,优于甲氨蝶呤(P<0.01)。在中医症候与中医症状总积分方面,风湿Ⅱ号胶囊疗效优于甲氨蝶呤(P<0.01);对于关节疼痛、关节肿胀、关节压痛、关节屈伸不利等症状来说,其疗效与甲氨蝶呤疗效相当(P>0.05);但对于晨僵、关节喜暖畏寒、畏恶风寒、腰膝酸软及神疲乏力等体现肾阳虚的特异性症状上,风湿Ⅱ号胶囊明显优于甲氨蝶呤(P<0.01)。在中医症状改善的起效时间上,关节疼痛、关节肿胀、关节压痛、关节屈伸不利及晨僵为8周(P<0.05);而关节喜暖畏寒、畏恶风寒、腰膝酸软及神疲乏力等症状从第4周就有明显改善(P<0.01)。实验室指标方面,风湿Ⅱ号胶囊在改善C反应蛋白(C reactive protein,CRP)与甲氨蝶呤疗效相当,而对于血沉(Erythrocyte sedimentation rate,ESR)及类风湿因子(Rheumatoid factors, RF)则无明显的治疗效果。比较两组治疗前后白细胞(White blood cell,WBC)变化,表明甲氨蝶呤能够导致白细胞总数降低,而风湿Ⅱ号胶囊则无此副作用。在毒副作用及不良反应发生率比较上,甲氨蝶呤组与风湿Ⅱ号胶囊组有统计学差异(P<0.05),提示在药物安全性方面,风湿Ⅱ号胶囊要优于甲氨蝶呤。
     在总结吉海旺教授治疗RA经验的基础上,根据现代RA的病因学、发生学和实验医学等的研究成果,结合自己多年的临床实践,发现RA在发病的过程中,不仅存在肾虚血瘀,而且由此而产生的“瘀毒”使该病的治疗更加复杂化,所以今后在治疗RA上,不仅应重视虚瘀同治,更应注重虚、瘀、毒并治,可能收到更为理想的疗效。
     综上所述,通过跟师学习,本文全面继承整理了吉海旺教授学术思想,系统研究了治疗类风湿性关节炎的临床经验,进一步验证了风湿Ⅱ号胶囊治疗RA的作用及机理,为类风湿性关节炎从肾论治提供了理论依据。
Rheumatoid arthritis (RA) is a symmetrical polyarthritis with the main clinical manifestations of autoimmune disease. The character is chronic inflammation of synovium of joint and progressive failure of joints. The clinical manifestation is changeable and poor prognosis. It appears ankylosis, abnormalities and function failure in advanced stage and it cause the impairment of heart, lung, kidney, other organs and multisystemic which will compromise to the patient's health and quality of life seriously. In northern of China, RA has the high incidence, therefore, the prevention and treatment of RA has important theoretical and social significance.
     In Traditional Chinese medicine. RA was always considered as "Bi-syndrome",,'obstinate arthralgia','rheumatism involving bone','rheumatism','crane-like arthropathy','drumstick wind'and etc. In modern TCM area. RA has been always diagnosed as'Wang bi' that established by Professor Jiao Shude.
     Professor Ji Haiwang (chief physician, doctoral supervisor) is committed to treatment and research of internal medicine disease for30years which focus on organ pattern identification, identify patterns and administer treatment according to bowels and viscera. He suggested several theories, such as improving spleen in treatment of cough, improving liver in treatment of chest-abdom fullness, improving spleen and kidney in treatment of gout, improving spleen and stomach in treatment of recurrent aphthous ulcer, improving liver, spleen and kidney in treatment of alopecia.
     Professor Ji Haiwang conducted in-depth study and had considerable achievements in the field of rheumatology research. He represented RA which caused by kidney asthenia and exogenous evil. The internal cause is the pathogenic foundation. The external cause is the significance factor which includes environmental factor (cold, wet), bacteria, viruses and etc. kidney asthenia includes not only asthenia of Native endowment but also disorder of immune function. According to his theory, it should oriented focus on Kidney in treatment of RA. Because invigorating the Kidney and essence replenishment could make up congenital asthenia, invigorating the Kidney and improving spleen could improve acpuired asthenia, invigorating the Kidney and could nourish liver could nourishing Yin and muscle, invigorating the Kidney and nourishing blood could enriched Yi and Wei, invigorating the Kidney and warming yang could promote blood circulation to remove meridian obstruction.
     According to development of RA, it has been divided into acute phase, sub-acute phase and chronic-phase by Professor Ji Haiwang. Base on the principle of therapy is treating tip in acute condition and treating root in chronic condition, we should remove heat to relieve convulsion and reinforce kidney and activating blood in the acute phase. Dispelling wind and eliminating dampness, tonifying kidney and activating blood analgesia in sub-acute phase. Reinforcing kidney and activating blood in chronic-phase. The characteristic feature on drug was the major drug was the wind-damp-dispelling medicinal in acute condition. The ratio of kidney yang-supplementing medicinal and blood-quickening medicinal gradually increased during the state of an illness worsening.
     This article validates the RA's determination of treatment rule of Professor Ji Haiwang according to retrospective and prospective clinical research. To utilize the clinical efficiency evaluation of Chinese Herbs Fengshi Ⅱ capsule in treatment with RA, it can certify the efficiency and safety of reinforcing kidney and activating blood in treatment with RA.
     Record the related clinical symptoms, signs, drug use and statistics analysis according to retrospective analysis of70RA patients. The incidence of kidney asthenia and blood stasis is50.00%, kidney asthenia and cold evil stasis is33.86%, damp-heat damaging kidney is7.14%. other pattern type is10.00%. It indicated the most frequent symptom is kidney asthenia and blood stasis. The major medication is damp-dispel agent&diuret, the minor is kidney-reinforcing drugs, the next is hemorheologic agent and the last medication is diaphoretics. The regular pattern of medication in treatment of RA is kidney asthenia and blood stasis combined with dispelling wind and eliminating dampness.
     According to observe the prospective studies in60RA patients (the medication of control group is Methotrexate Tablets), we observed the efficiency and safety of Fengshi Ⅱ capsule in treatment of RA. The result:the total effective rate of Fengshi Ⅱ capsule was96.67%, there was statistical significance between two groups (P<0.05). The effective of Fengshi II capsule is better than Methotrexate Tablets. In the further comparison with two groups, there was significant same effect in pain, tenderness of articular, articular edema, early morning stiffness and average hand strength of RA (P<0.01). Otherwise, there was statistical significance between two groups in articular edema. Compared to methotrexate, Fengshi II capsule had the same effect on the symptoms of the patients such as rest pain, articular edema index, articular pain and articular flexion-extension dysfunction, but had better effect on kidney-yang deficiency including morning stiffness duration, aversion to wind and cold, lassitude in loins and weakness and tiredness after8weeks of treatment. Compared to methotrexate group, the level of CRF had no statistical significance in Fengshi Ⅱ capsule. However, the levels of erythrocyte sedimentation rate (ESR) and rheumatoid factor (RF) hadn't changed in both group. The levels of WBC before and after treatment in the two groups were compared between the two groups, there was statistical significance in methotrexate group (P<0.05), however, there was no obvious difference in Fengshi Ⅱ capsule group. As a result, methotrexate can cause a decrease in the level of WBC, but no this side effect in Fengshi Ⅱ capsule group, in another word, Fengshi Ⅱ capsule was more safely than methotrexate. The method of nourishing kidney and activating blood emphasis the advantages of TCM in treatment of RA, and embody the superiority of abidance by triple pathogens and syndrome differentiation and treatment.
     According to the clinical experience of Pro.Ji and the research results of etiology, genetic principle and experimental medicine, the author considered that there is not only kidney asthenia and blood-stasis but also toxicity which could result the complication of disease in the pathogenesis of RA. As a result, on the basis of reinforcing kidney and activating blood, the application of dissolving blood stasis and detoxication could be added properly.
     In a word, the objective of this study is to research systematically the treatment experience of RA by learning and arranging the academic thought of Pro.Ji Hai-wang. In addition, the study is to verify the effect and mechanism of Fengshi Ⅱ capsule on RA and provide the evidence for the treatment from kidney.
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