补肾泄毒颗粒治疗慢性肾衰的疗效观察及对血清PTH、EPO的影响

【作者】 金俊佑；

【导师】 聂莉芳；

【作者基本信息】 中国中医科学院 ， 中医内科学， 2009， 博士

【摘要】 慢性肾功能衰竭是多种肾脏疾病发展的最终结局,是临床常见的疑难病。研究包括中医药治疗在内的慢性肾衰非透析疗法以延缓病情发展具有十分重要的意义。本论文主要包括文献研究、经验继承和临床研究三部分。文献研究部分有二篇。第一篇“慢性肾衰的中医研究进展”主要介绍中医对慢性肾衰的认识、中医临床治疗慢性肾衰现状和有关中药作用机理研究的进展。中医学无“慢性肾功能衰竭”的名词,但古代文献中的“癃闭”、“肾风”、“关格”所描述的病症,与慢性肾衰患者的临床表现是很相似的。中医认为本病进展有内外两方面的因素:内因主要为肾气不足,外因多为外感六淫之邪、皮肤疮毒、肾毒性药物侵犯肾脏。肾病既久,失治误治,导致肾阳衰微,真阴亏耗,致使肾脏本身功能日益衰退,气血阴阳虚惫,肺脾心肝为之虚损,属本虚标实、虚实夹杂之证。其治疗主要包括中医辨证论治,基本方基础上随症加减,单味药及有效成分(主要为大黄和冬虫夏草),其它疗法如灌肠疗法、中药结肠透析、药浴及泡足疗法、中药穴位外敷法、隔药灸疗、超声激光疗法等。中医药治疗慢性肾衰的作用机理主要集中在抑制肾小球系膜细胞的异常增殖及细胞外基质的过度积聚、调控细胞凋亡、调节血管活性物质、影响细胞因子、改善肾小球血液动力学、清除氧自由基等几个方面。第二篇“慢性肾衰的现代医学认识及相关研究进展”主要介绍了现代医学对慢性肾衰的有关认识,尤其是慢性肾衰非透析治疗的临床现状。慢性肾衰病因分原发性和继发性肾脏病两大类,原发性肾脏病主要有慢性肾小球肾炎、慢性肾盂肾炎、慢性间质性肾炎等,继发性肾脏病主要有代谢异常所致的肾脏损害、血管性病变、遗传性肾病、中毒性肾病及梗阻性肾病等。其发病机理主要包括健存肾单位学说、矫枉失衡学说、肾小球高滤过学说、肾小管高代谢学说、脂代谢紊乱学说、尿毒症毒素学说等,近年来则认为细胞因子和生长因子在慢性肾衰进展中也扮演着重要的角色。其治疗主要为慢性肾衰的一体化治疗,主要包括饮食控制与营养疗法、全身及肾小球局部高压的控制、抗凝和抗血小板治疗、降脂治疗等。经验继承部分,题为“导师聂莉芳教授治疗慢性肾衰的临床经验”。主要从慢性肾衰的中医病名分期、病因病机、治疗方法等方面总结整理导师聂莉芳教授治疗慢性肾衰的临床经验。导师通过病名的整理研究,认为慢性肾衰的中医病名以关格较为恰当,因为它集中地突出了慢性肾衰终末期,由于正虚至极,枢机不利,气机升降失司,三焦壅塞这一病理机转所反映的临床特点。同时关格一病,历代医家向来认为是疑难重症,这对于判断预后是有一定意义的。导师认为慢性肾衰的病因有主因与诱因之分。主因多系脾肾虚损,与先天不足、饮食失常、七情内伤、久病失治、房劳过度等多种因素耗伤正气有关,其中尤以肾气衰惫,分清泌浊失职,致使湿浊内停为主;诱因则责之外邪与过劳。导师将慢性肾衰的中医病机概括为本虚标实、寒热错杂、病位广泛,其中本虚标实、正虚邪实为本病的病机中心。鉴于慢性肾衰在病程中有虚实主次及标本缓急之异,导师于1984年在国内率先提出了对关格病中医临床分期的学术观点,将关格病(慢性肾衰)分为虚损期、关格期两期。导师认为分期对临床具有重要的指导意义:①对其病机、临床表现特点及发展变化的规律等方面的认识具有整体观念,从而对论治具有整体性的指导意义;②有利于关格病辨证论治的规范化研究及治疗方案的优化;③有利于对预后的判断。导师临床治疗本病的思路是:首辨病期,然后细细辨证,将辨病期与辨证有机地结合起来,继之选择治法与相应的方药。而且还强调病期与证型可分而不可定,应同时注意其动态变化的情况。导师强调气阴两虚在慢性肾衰虚损期中最为多见,在此基础上,同时要细辨究竟是心肾气阴两虚、肺肾气阴两虚、脾肾气阴两虚、肾气阴两虚、肝肾气阴两虚其中的哪一种类型,同时在气阴两虚的程度方面又细分为气阴两虚偏于气虚、气阴两虚偏于阴虚、气阴两虚并重三种情况。之后,在临床上根据患者的实际情况予以恰如其分的治疗。导师认为关格期是慢性肾衰的终末期阶段,患者的临床表现具有典型的下关上格的关格病特征,病机特点以湿浊、湿热中阻为主,治法则当以救治脾胃为主。导师强调针对上格,调理脾胃法疗效可靠,常可转危为安。临床研究部分,题为“补肾泄毒颗粒治疗慢性肾衰的疗效观察及对血清EP0和PTH的影响”。目的:观察补肾泄毒颗粒(导师经验方)治疗慢性肾衰的临床疗效及对血清EPO和PTH的影响。方法:纳入60例慢性肾衰患者,按照2:1比例,随机分为治疗组(40例)和对照组(20例),治疗组给予补肾泄毒颗粒,对照组给予尿毒清冲剂,两组患者均予基础治疗(包括饮食及对症治疗)。1个月为1个疗程,共治疗2个疗程。观测临床症状、肾功能、血红蛋白(Hb)和红细胞压积(HCT)变化,并观察补肾泄毒颗粒治疗43例患者治疗前后血清甲状旁腺激素(PTH)和促红细胞生成素(EPO)的变化。结果:在疾病疗效方面,治疗组总有效率为80.75%,对照组为65.00%,两组之间有显著性差异,P＜0.05,提示在疾病疗效方面,治疗组显著优于对照组。在中医证候疗效方面,治疗组总有效率为87.50%,高于对照组55.00%,有显著性差异,p＜0.05。两组病人经治疗后,血红蛋白水平和红细胞压积显著提高,血肌酐、血尿素氮水平显著降低,且治疗组作用优于对照组,有显著性差异,p＜0.05,p＜0.01。经补肾泄毒颗粒治疗后,43例慢性肾衰伴有肾性贫血的患者的血清EPO水平明显升高,与治疗前比较有显著性差异,P＜0.01,治疗后血清PTH、P均有明显下降,而Ca升高,与治疗前比较有显著性差异,P＜0.01。结论:补肾泄毒颗粒不仅能够显著改善慢性肾衰患者的临床症状和体征,改善肾功能,纠正肾性贫血和升高血清EPO水平,并具有抑制慢性肾衰患者高PTH血症,调节钙磷代谢失调的作用,延缓慢性肾衰的病程进展。更多还原

【Abstract】 Chronic renal failure, being a common obstinate disease clinically, is the ultimate outcome of multiple renal diseases. The study of non-dialysis therapy for chronic renal failure, including the application of traditional Chinese medicine, has significant meaning in delay the development of disease progress.This study consists three main part including reference research, experience inheriting and clinical research.In the reference research part, there were two major references. The first one, "The study development of therapy approach for chronic renal failure using Traditional Chinese Medicine", mainly introduced the opinion of Traditional Chinese Medicine for chronic renal failure, the current situation of chronic renal failure therapy using TCM clinically and the development of mechanism for Chinese herbal medicine functioning. The second reference, "the related research development of opinion in modern medicine for chronic renal failure", mainly discussed the opinions for chronic renal failure in the angle of modern medicine, and especially highlighted the current clinical situation of non-dialysis therapy for chronic renal failure.In the experience inheriting part, named after "Clinical experience in chronic renal failure therapy of Prof. Lifang Nie". In this part, we discussed the disease name and stage in Traditional Chinese Medicine, etiology and pathogenesis, therapy method for chronic renal failure, and summarized the clinical experience of Professor Lifang Nie in treatment of chronic renal failure. My tutor thinks that it is more appropriate to name chronic renal failure as GuanGe in TCM through the collation of disease research.And tutor believes that the cause of chronic renal failure include primary cause and remote cause. The clinical approach of my tutor treating chronic renal failure is discrimination of the disease period at first, and then careful differentiation, combination of above both finally.In the study part, named as "the observation on therapeutic effect and impact on serum EPO and PTH after application of Bu-shen-xie-du granule in therapy of chronic renal failure". Objective: To observe the clinical effect and impact on serum EPO and PTH in renal failure patient after using Bu-shen-xie-du granule (experience preparation of supervisor). Method, There were 60 chronic renal failure cases which was randomly divided into two groups with 2:1 proportion: therapy group (40 cases) and control group (20 cases). Bu-shen-xie-du granule was applied for the therapy group, and Niao-du-qing granule for control group. For all patients in both groups, they accepted same basic therapy (including diet and symptomatic treatment). The treatment course was 8 weeks, the changes in clinical symptom, renal function, hemoglobin (Hb) and hematocrit (HCT) were observed. We also detected the serum PTH and EPO before and after the application of Bu-shen-xie-du granule in treatment of chronic renal failure (n=43). Result: the total effective rate was 80.75% in therapy group, and 65.00% in control group, with significant difference between two groups, P<0.05, which suggested the better effect of therapy group compared with control group. In the treatment of syndrome, the overall effect rate in therapy group was 87.50%, higher than the 55.00% in control, with significant difference, P<0.05. After the treatment in both groups, the hemoglobin level and hematocrit were prominently elevated, serum creatine and BUN level were decreased obviously, but the effect in therapy group was better than control group with significant difference, P<0.05, P<0.01. After treatment with Bu-shen-xie-du granule, the chronic renal failure patients with renal anemia (n=43) has shown elevation of serum EPO level, with significant difference compared with before treatment, P<0.01. After therapy, the serum PTH was significantly decreased accompanied with the elevation of calcium level, which proved to have significant difference, P<0.01. Conclusion: Bu-shen-xie-du granule not only has the effect to improve the clinical symptom and physical sign for chronic renal failure patients, improve renal function and correct renal anemia as well as elevate EPO level, but also can inhibit the high PTH disease in chronic renal failure patients, modulate the disordered calcium-phosphate metabolism, and delay the progress of chronic renal failure.更多还原