从气血水理论探讨益气活血利水法治疗特发性膜性肾病的研究

【作者】 马雪玲；

【导师】 占永立；

【作者基本信息】 北京中医药大学 ， 中西医结合内科， 2010， 硕士

【摘要】 特发性膜性肾病(IMN),是我国最常见的原发性肾小球疾病之一,同时也是成人原发性肾病综合征最常见的原因。本病自然病程波动,预后影响因素较多,尽管在肾小球疾病的研究中,对IMN治疗的研究是最集中的,国内外专家对不同风险IMN患者的治疗达成一定的共识,但仍然存在着很大的争议,目前尚无疗效确切而满意的治疗方案。因此对治疗方案的选择、治疗时机的把握以及治疗风险的评估,始终是临床医师深感困惑的问题。中医药治疗膜性肾病有着较好的疗效,尤其在减少复发、减轻临床症状以及减低西药的毒副作用方面有着独特的优势。但也存在着辨证分型繁杂而不统一,临证参照困难等问题。导师在中医经典理论的指导下,总结中医治疗IMN的经验,结合临床实践,从气血水理论进行论治,化繁为简,认为气虚血瘀水停是其基本病机特点,初步形成了以益气活血利水为法的治疗思路,临床取得了较好的疗效。目的：回顾性分析益气活血利水法治疗IMN的临床疗效,从气血水理论初步探讨IMN的中医基本病机,为益气活血利水法治疗IMN提供理论依据和研究思路。方法：1.采用自身前后对照的研究方法：观察55例患者治疗前后中医证侯积分、24小时尿蛋白定量、血浆白蛋白及肾功能的变化,评价疗效。2.分层分析：依据24小时尿蛋白定量水平分层后,采用组间对照的研究方法,观察中药组与中药加用免疫调节治疗组治疗前后中医证侯积分、24小时尿蛋白定量、血浆白蛋白及肾功能的变化。结果：1.55例IMN患者疗效评价：①综合疗效：治疗6个月、12个月以及24个月以上总有效率分别为51.5%,73.1%和87.5%。其中24个月以上临床痊愈率为62.5%。高于文献报道的自发缓解率14%-56%。②中医证侯疗效：治疗6个月、12个月以及24个月以上总有效率分别为72.7%,84.6%和95.8%。③24小时尿蛋白定量疗效：治疗6个月、12个月以及24个月以上,总有效率分别为54.5%,76.9%和91.7%。④主要中医症状改善较为明显者有水肿、乏力、纳呆、自汗、腰膝酸软等,其中疗程12个月以上总体症状改善更为明显,超过50%的患者临床症状消失。2.分层比较结果：依据24小时尿蛋白定量分层：①蛋白定量<3.5g患者：中药组17例,中药加免疫调节治疗组8例。两组中医证侯疗效分析：总有效率前者为94.1%,后者为87.5%；24hUpro疗效,前者为88.2%,后者为87.5%。②蛋白定量3.5g-6g患者：中药组8例,中药加免疫调节治疗组14例。两组中医证侯疗效分析：总有效率前者为87.5%,后者为87.5%；24hUpro疗效,前者为75%,后者为78.6%。不论是24hUpro<3.5g/d,还是24hUpro在3.5-6g/d的患者,两种治疗方案疗效无差异(P>0.05)。尿蛋白定量>6g患者仅有7例,中药组仅有1例,未进行组间比较。结论：1.从气血水理论探讨IMN的中医基本病机,气虚血瘀水停是其基本的病机特点。2.益气活血利水法治疗IMN具有较好的疗效,并且随着疗程的增加,有效率及完全缓解率逐渐升高,短期内在改善临床症状以及升高血浆白蛋白水平上疗效显著。3.本研究中24小时尿蛋白定量<6g的患者中药组及中药加用免疫调节治疗组,疗效比较无差异,对于中低危患者是否应该积极加用免疫调节治疗,提出思考,是否可予中药治疗,并适当延长观察时间至1年,有待进一步扩大病例数,开展多中心前瞻性随机对照研究,提供更可靠的临床依据。更多还原

【Abstract】 Idiopathic membranous nephropathy (IMN) is one of the most common primary glomerular diseases in China and the most common cause for nephrotic syndrome in adults. The natural course of IMN is variable and a number of factors have been claimed to be able to affect the prognosis of IMN, besides, the treatment with immunosuppressive agents is not so effective. Although of all glomerular diseases, the management of membranous nephropathy has been most intensively studied, yet remains greatly controversial, which makes the clinician more confused in clinical practice. Though experts in and abroad have reached in an agreement of the treatment based on the vary degrees risk of progression, yet whether, how and when to treat IMN patients with a specific therapy is still a matter of controversy. Chinese medicine shows advantages in treating IMN,especially in reducing replase rate, relieving clinical symptoms and reducing the side effects of immunosuppressive agents. However there are still several problems which requires us to solve, such as the syndrome differentiation is quite complicated which increased the difficulty of clinical reference. My tutor, doctor zhanyongli, the chief physician, belives that we should makes the syndrome differentiation more simple and easy to follow from the theory of Qi-Blood-Water based on classic theory of Traditional Chinese Medicine. After years of clinical practice and the summary of contemporary Chinese clinicians’experience, he belives that the basic pathogenisis of IMN in Chinese medicine is qi-difficiency blood stagnation and water retention and gradually forms an initial treatment principle, that is reinforcing qi, activting blood circulation and removing water retention, which shows good effect on treating IMN. Our study is to evaluate the therapeutic effect by reviewing 55 IMN cases treated with the principle of reinforcing qi, accelerate blood circulation and removing water, meanwhile to lay the foundation for further clinal and experimental studys.Objective:To evaluate the therapeutic effect of Yiqihuoxuelishuifa in treating IMN. And a preliminarily discussion of the basic pathogenesis of IMN in TCM, that is qi-difficiency blood stagnation and water retention based on the theory of qi, blood and water in traditional Chinese medicine, meanwhile provided the theoretical basis for the treatment principle of Yiqihuoxuelishuifa on IMN.Methods:(1) Using retrospective self controlled study to analyze the therapeutic effect of 55 IMN patients as a whole group, observing pre and post scores of Chinese syndrome 24hUpro, ALB and the changes of renal function,to evaluate the general therapeutic effect. (2) The stratified analysis:Using inter-group controlled methods to compare the therapeutic effect between the group treated with Chinese medicine and those with Chinese medicine combined with immunosuppressive agents based on the same level of 24hUpro, observing pre and post scores of Chinese syndrome 24hUpro, ALB and the changes of renal function, to evaluate the general therapeutic effect.Results:(1) Therapeutic effect:analyzing 55 IMN patients as one group:①general therapeutic effect:the total effective rate is 51.5%,73.1% and 87.5% in the treatment courses of 6 months course,12 months and over 24 months. The complete remission rate is 62.5% at the group that over 24-month-treatment course, higher than reported spontaneous remission rate of 14%-56%.②Effect evaluated by score changes of Chinese syndrome:the total effective rate of is 72.7%,84.6%, and 95.8% in the treatment courses of 6 months course,12 months and over 24 months.③Effect evaluated by the change of 24hUpro:the total effective rate of is 54.5%,76.9%, and 91.7%. in the treatment courses of 6 months course,12 months and over 24 months.④The main clinical symptoms have greatly improved after treatment are edema, acratia, anorexia, spontaneous perspiration and sorness and weakness of back and knee,. Of all the patients, whose treatment course is over 12months, have better effect. More than 50% of them got toltal the clinical syndromes release.⑤The level of 24hUpro and ALB both have significant changes compareing with pre-post treatment (P<0.01).(2) The stratified analysis results:based on the level of 24hUpro:①24hUpro<3.5g cases:17 cases were treated with Chinese medicine,8 cases were treated with Chinese medicine and immunosuppressive agents. a) Effect evaluated by score changes of Chinese syndrome:the total effect rate is 94.1% and 87.5%. in the group treated with Chinese medicine and that combined with immunosuppressive agents. b) Effect evaluated by 24hUpro:the total effect rate is 88.2% and 87.5%. in the group treated with Chinese medicine and that combined with immunosuppressive agents.②24hUpro in the range of 3.5-6g:8cases were treated with Chinese medicine,14 cases were treated with Chinese medicine and immunosuppressive agents. a) Effect evaluated by score changes of Chinese syndrome:the total effect rate is 87.5% and 85.7%. in the group treated with Chinese medicine and that combined with immunosuppressive agents. b) Effect evaluated by 24hUpro:the total effect rate is 75% and 78.6% in the group treated with Chinese medicine and that combined with immunosuppressive agents. In a word no matter 24hUpro<3.5g, or 24hUpro in the range of 3.5-6g no difference was found between the two treatment protocols (P>0.05).Conclusion:1. The basic pathogenesis of IMN in TCM is qi deficiency, blood stasis and water retention, based on the classic theory of qi blood, and water.2. It shows quite prospective effects of the treatment principle of Yiqihuoxuelishui on IMN. The longer treatment courses we gave the patients, the better therapeutic effect and higher complete remission rate they got. In the short courses there shows better effect in improving clinical symptoms and in increasing ALB.3. There was no difference between the group treated with Chinese medicine and those with Chinese medicine combined with immunosuppressive agents, among the patients whose 24hUpro less than 6 gram. This result shows us the hints that whether we should treat the patients in low and middle risk with immunosuppressive agents, yet remains controversial. We could enlarge our cases and carry out a multi-center prospective randomized controlled clinical research, thus to provid more reliable clinical evidence in the future.更多还原