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裴正学教授治疗再生障碍性贫血学术思想初探
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摘要
目的:本课题通过临床观察系统总结裴正学教授治疗再生障碍性贫血的经验,挖掘裴老治疗再生障碍性贫血辨病与辩证相结合的新的辩证思维模式,即在西医诊断的前提下进行中医辩证,才能药中病的,提高临床疗效,总结教授治疗再生障碍性贫血独特的用药特点及规律。
     方法:1.理论研究方法(1)全面汇总、整理、归纳裴正学教授临床资料,通过分析总结裴教授治疗慢性再生障碍性贫血的临床经验,从理论上加以总结、凝练,挖掘出教授治疗再障的理论精髓。(2)在临床实践中体会裴正学教授提出的发展中医的十六字决:“西医诊断、中医辨证;中药为主、西药为辅”,领会其理论精髓,将其精神贯穿在再生障碍性贫血的理论探讨及临床实践中。2.临床研究方法:将符合纳入标准的68例慢性再障患者分为观察组和对照组,观察组53例,对照组15例,依据其具体的中医辨证分型(依照1989年中国中西医结合血液病座谈会提出的慢性再障分型以肾为主的原则,分为肾阴虚型、肾阳虚型和阴阳两虚型)遣方用药,分别采用当川合剂加减联合司坦唑醇加环孢素A治疗;对照组15例,单纯采用司坦唑醇加环孢素A治疗,两组的治疗疗程均为6个月以上。观察两组患者治疗前后临床疗效、中医证候的改善情况、外周血细胞计数、肝功能的变化情况。
     结果:1.理论研究结果:(1)裴正学教授认为治疗再生障碍性贫血关键是补肾健脾、活血化瘀、清热解毒。补肾为主,键脾为辅;活血化瘀、清热解毒贯穿始终;缓则健脾补肾、活血化瘀,急则清热解毒、泻火止血,并提出再生障碍性贫血毒入骨髓的病因病机,清热解毒可以生血的治疗方法。
     根据肾主骨、藏精生髓、髓血同源的中医理论及再生障碍性贫血的病理基础是骨髓造血功能衰竭的现代医学观点,裴老认为再生障碍性贫血的根源在于肾,肾虚为再生障碍性贫血之根本,临床上应把传统的中医辩证和现代医学紧密结合起来,即辨病辨证相结合,病证结合、辨证施治,实现个体化用药,把补肾贯穿于再生障碍性贫血治疗的始终。
     脾为后天之本,水谷之海,气血化生之源。脾虚气血生化无源,可致气血不足而出现头晕乏力、面色不华等贫血症候;脾虚统血无权,血溢脉外而出血。“气为血帅、血为气母”,裴老把补气生血、摄血之法溶于再障治疗当中,补气重用太子参、人参须。
     裴老发现清热解毒法可以提高再障患者血小板,结合再生障碍性贫血患者急性期血热妄行的病机,用清热解毒、凉血止血的治疗原则,以方测证,提出再生障碍性贫血毒入骨髓的病机,把清热解毒之法用于再生障碍性贫血的治疗,发现清热解毒之法,不仅在急性期有泻火止血的作用,在稳定期尚有生血的作用,提出再生障碍性贫血毒入骨髓的病机,清热解毒可以生血的治疗方法,并把清热解毒的治疗方法贯穿于治疗再生障碍性贫血的始终,常用土大黄、黄连、黄芩、金银花、连翘、蒲公英、败酱草之属。
     裴老认为淤血不去,新血断无再生之理,治疗再生障碍性贫血常加入活血化瘀药(如川芎、丹参、赤芍、当归、鸡血藤、三七、水蛭),尤其重视水蛭,水蛭破血逐瘀,裴老认为此药能增加患者之恢复速度,促进患者向愈。瘀血既是再生障碍性贫血发病过程中的的病理产物,出现在再生障碍性贫血发病过程中的任何一个阶段,同时又可作为一种致病因素而加重出血,诱发感染,形成恶性循环,变证百出,缠绵难愈。
     裴老认为,治疗再生障碍性贫血宜与现代医学提供的各种微观资料相结合。再生障碍性贫血白细胞低下突出者多表现为神疲乏力、少气懒言,属气虚,重用人参须、太子参、黄芪等益气之品,并总结出升白五药:破故纸、鸡血藤、丹参、苦参、黄精;红细胞低下突出者多表现为头晕目眩、面色苍白,属血虚,重用生地、首乌、女贞子、黄精、旱莲草、玉竹、大枣、阿胶等养血之品;血小板低下者表现为齿衄、鼻衄、皮下瘀斑等等,裴老总结出升板五药:玉竹、黄精、地黄、连翘、土大黄。治疗再生障碍性贫血升白细胞见效快,而升红细胞、血小板当以坚持服药方能收效。
     “肾,主骨,生髓”,裴老认为再生障碍性贫血骨髓造血干细胞损伤者多与中医所说的肾虚有关;“脾主统血”,再生障碍性贫血属于免疫功能介导者多与中医所说的脾虚有关;清热解毒之品亦与免疫有关,类似于免疫抑制剂的作用;骨髓微循环障碍者多与中医所说的瘀血内阻相关。所以,裴老在辨证论治的基础上,结合现代医学对再生障碍性贫血的病理分型及现代中药药理研究成果,遣方用药,集补肾、健脾、活血化瘀于一炉,以期达到再生障碍性贫血多靶点治疗日的。
     (2)裴正学教授提出的“西医诊断、中医辨证;中药为主、西药为辅”为发展中医指出了有效途径。
     教授以“西医诊断,中医辨证;中药为主,西药为辅”为指导思想,充分利用现代医学的诊断优势,将疾病定位、定性,把握再生障碍性贫血发生、发展及其演变规律;临床治疗中将辨证与辨病有机地结合在一起。西医诊断,中医辨证的临床诊断方法,使得中医辨证能够准确把握某种疾病特定阶段的证,获得更好的临床疗效,是望闻问切检查方法的延伸,是对中医诊断学的发展。“中药为主”,就是在治疗疾病时,主要采用中药为主的方法,突出中医药的地位,不要把中医定位为辅助治疗的地位,坚持中西医并重的发展战略,要把中医传统理法方药完全贯彻进去,使几千年的中医方药的理论实践得以继承;“西药为辅”,是指有一些疾病西医药有明显的优势,我们要取其所长,为我所用,做到优势互补。
     2.临床研究结果经临床研究,观察组西医疗效总有效率(缓解+明显好转)为79.24%,明显优于对照组总有效率60.00%,二者之间存在显著性差异(P<0.05);观察组中医证候综合疗效总有效率(临床痊愈+显效+有效)为83.01%,明显优于对照组总有效率53.33%,二者之间存在显著性差异(P<0.05);观察组的中医证候积分改善显著,明显优于对照组(P<0.05);外周血象比较(WBC、HB、PLT计数)治疗前两组无显著差异(P>0.05),治疗后两组均有升高,但观察组升高明显,二者之间存在显著性差异(P<0.05);观察组治疗后CD+3、CD+4值升高,CD+8值降低,与治疗前比较有显著性差异(P<0.05),对照组治疗CD+3、CD+4值减低,CD+8值升高,差异有显著性;通过两组治疗后患者肝功能的观察,两组均无明显改变,且无显著的差异(P>0.05)。
     结论:临床研究证实当川合剂为主联合司坦唑醇、环孢素A治疗慢性再障患者,可有效改善患者的临床症状(主要是中医症候)及外周血象,调节机体免疫力,且对肝功能无明显损害,可以明显改善患者生存质量。
     本研究提示中医治疗慢性再生障碍性贫血的可能机理是:
     1.补肾健脾中药有促进骨髓干细胞发育的作用。
     2.通过调整患者T细胞亚群,纠正T细胞免疫功能紊乱,从而解除对骨髓造血功能的抑制而达到治疗效果。
     3.通过活血化瘀改善骨髓造血微环境。
     4.清热解毒促进再障患者骨髓造血。
     笔者对再生障碍性贫血研究的创新点及思考:
     1.通过对裴教授治疗再障用药特色的挖掘,得出结论:清热解毒可以生血,清热解毒不仅仅是再障患者出血或者有出血倾向时的治疗原则,清热解毒本身可以促进再障患者骨髓造血。2.疗效的判定应该结合中医的判断标准,中医药在改善患者生存质量方面的作用不能忽视,所以不能单纯按西医的疗效标准来判断疗效。3.再障具有区别于其他“虚劳”证候的特点,其病机基础和辨证体系当有其特殊性。4.再障的中医辨证分型和辨证分型的物质基础要深入研究,揭示再障的症候的本质,用微观指标确定下来,指导临床用药,切实提高疗效。5.在研究方法和手段上应该实验和临床相结合,一方面探索更客观实际的模型制作手段,另一方面加强临床方面的观察研究,使临床疗效具有较好的可靠性和重复性。6.在实验水平上,再生障碍性贫血的中医药疗效机理的研究须不断借鉴中医药和现代医学最新的研究方法和思路,如分子生物学、细胞凋亡、细胞周期、蛋白表达和中药血清药理学等方面进行结合研究。7.西医辨病与中医辨证的有机结合,一方面促进了中医临床研究的发展,但对中医个体化诊疗的特色造成一定不利的影响。8.目前普遍的把中医药治疗仅作为辅助手段,而对于积极寻找与西医在临床治疗上的互补点重视不够。
Objective:Firstly, Professor Pei Zheng-xue's clinical experience on treatment of aplastic nemiais is summarized through the author's clinical observation. Secondly, Professor Pei's dialectical thinking scheme on the treatment of aplastic anemia is analyzed in this paper. For the purpose of improving the therapeutic effect, traditional Chinese medicine (TCM) syndrome differentiation and treatment should be followed after the Western medicine diagnosis. At last, this paper summarizes Professor Pei's unique herbs administering characteristics and rules.
     Methods:
     1. Theoritical Research Methods:(1) Professor Pei's essence theory for the treatment of aplastic anemia is condensed and excavated by comprehensively summarizing, sorting and inducting his clinical data, along with the analyzing and summarizing his clinical experience in the treatment of chronic aplastic anemia.(2) From the clinical practice point of view, Professor Pei Zheng-xue's theory on the development of Chinese medicine can be summarized into'Diagnosed by Western medicine; Discriminated by traditional Chinese medicine; TCM should be as the fundamental treatment method while Western medicine diagnosis as the supplemented way'. Finally, the essence of the theory has to be put into theoretical study and clinical practice.
     2. Clinical Research Methods:68cases of chronic aplastic anemia patients were divided into treatment group (53cases) and control group (15cases), separately. Depending on their specific TCM syndromes, the treatment groups can be divided into three types, namely, kidney yin, kidney yang, both kidney yin and yang. The prescription contained dangchuanheji, stanozolol, and cyclosporin A. Regarding to the control group (15cases), the prescription only contained pure stanozolol and cyclosporine A. The treatment period of the two groups are lasted over6months. The clinical efficacy of the TCM symptom improvements in peripheral blood cell counts, peripheral blood and bone marrow blast percentage, and liver function are observed during the treatment process, and are compared with the condition before the treatment.
     Results:
     1.Theoritical Research Results:(1) Professor Pei holds the view that the key methods to treat aplastic anemia are tonifying kidney and strengthening spleen, promoting blood and removing blood stasis, as well as clearing heat and removing toxin. Tonifying kidney plays the dominant role in the treatment process, with strengthening spleen as the subsidiary means. Meanwhile, promoting blood and removing blood stasis run through the whole treatment process. Tonifying kidney and strengthening spleen, promoting blood and removing blood stasis are used in mild cases, whereas cleaning heat and removing toxin, clearing heat and stopping bleeding are used in emergency cases. Professor Pei also explained that the cause and the process of aplastic anemia are due to the toxin invading bone marrow. He pointed out that clearing heat and removing toxin can help blood generation.
     According to the TCM theory:Kidney governs bone, bone stores up marrow, marrow and blood are from the same source. From modern medical point of view, the pathological basis of aplastic anemia is bone marrow failure. Professor Pei holds the view that aplastic anemia is rooted in the kidney. The traditional Chinese medicine dialectical and modern medicine diagnosis should be closely combined in the treatment of aplastic anemia. In other words, tonifying kidney should be kept on during the whole treatment process of aplastic anemia. In order to achieve individualized medicine, we should systematically take the syndrome differentiation, disease and syndrome, syndrome differentiation into consideration. The spleen is the foundation of after birth, and is the source of Qi and blood. Pixu (spleen deficient) will lead to Qi and blood deficiency, thus results in dizziness, fatigue, anemia symptoms. Pixu (spleen deficiency) will not be able to control blood, therefore, it can lead to bleeding.'Qi is the head of the blood, and blood is the carrier of Qi Professor Pei used the method of strengthening spleen in the treatment of aplastic anemia. The commonly used herbal formula are Taizishen and ginseng.
     Professor Pei found than the detoxification method can improve aplastic patients' platelet. Combining with the pathogenesis on the aplastic anemia, and the detoxification, cooling hemostatic treatment principles, Professor Pei considered that the marrow toxicity is one of the pathogenesis of aplastic anemia. Then, he used the detoxification method to treat the aplastic anemia patients. It is found that detoxification method not only can reduce intense heat and stop bleeding, but also can generate blood during the slationary phase. Pei holded the point that the marrow toxicity is one of the pathogenesis of aplastic anemia, detoxification method can be used as the treatment. The etoxification method is lasted during the whole treatment process. He used soil rhubarb, coptis, scutellaria root, honeysuckle, dandelion, forsythia, herba patriniae etc as the prescription for the treatment of aplastic anemia.
     Professor Pei held the view that if congestion doesn't eliminate, the new blood will not be produced. Therefore, blood circulation drugs are often used in the treatment of aplastic anemia, such as chuanxiong, red sage root, red peony root, angelica, millettia, panax notoginseng, leeches and so on. Pei paid particular emphasis on leech, he believed that this drug can increase the patient's recovery speed, and promote the healing of patients.
     Blood stasis is the pathological product of the pathogenesis of aplastic anemia, it can occur at any time in the pathogenesis of aplastic anemia. Besides, it is the risk factor that can increase the bleeding, induce infection and create a vicious cycle.
     Professor Pei believed that the traditional Chinese medicine should be combined with the variety of micro-data of modern medicine for the purpose of treating aplasitc anemia. The patient with low white blood cells is characterized by fatigue, not to like to talk more. This phenomenon is defined as Qi (gas) deficiency. For the improvement of the illness, large dose of the drugs that are beneficial to Qi should be used, such as ginseng, radix pseudostellariae, dangshen, astragalus membranaceus etc. He also generalized five drugs that can increase white blood cells, namely, breaking paper, millettia, salvia, flavescens, polygonatum, etc. The patient with low red blood cell is characterized by dizziness, pale face, blood deficiency. For the improvement of the illness, large dose drugs that are beneficial to blood should be used, such as rehmanniae, polygonum multiflorum, ligustrum, eclipta, polygonatum, polygonatum odoratum, jujube, donkey-hide gelatin and so on. The patient with low platelet is characterized by gingival hemorrhage, epistaxis, subcutaneous ecchymosis, and so on. Professor Pei generalized five drugs for increasing blood platelet, namely, polygonatum odoratum, polygonatum, rehmannia root, forsythia, Tu Dahuang, soil rhubarb. The white blood cell can rise fast during the treatment of aplastic anemia. However, the rising speed of red blood cells and platelets is slowly compared with white blood. Therefore, after a long period of medication, the treatment efficacy can be achieved.
     'Kidney governs bone, bone stores up marrow'. Professor Pei thought that the aplastic anemia patients with the bone marrow hematopoietic stem cell damaged were mostly related to kidney.'Spleen controls the blood', the aplastic anemia patients with immune function mediated were mostly related to spleen. Detoxification drugs should be related to the immune system, which is similar to the immunosuppressant. The patients with bone marrow microcirculation were mostly related to bleeding resistance. So, based on Professor Pei's diagnosis and treatment theory, we should combine the modern medical pathology and pharmacology research results on the treatment of aplastic anemia, and synthetically consider tonifying kidney and strengthening spleen, promoting blood and removing blood stasis at the same time, so as to achieve the multi-target on the treatment of aplastic anemia.
     (2) Professor Pei Zheng-xue's theory point out a effective way for the development of traditional Chinese medicine, that is'Diagnosed by Western medicine; Discriminated by the traditional Chinese medicine;TCM should be as the fundamental treatment method while Western medicine diagnosis as the supplemented way'
     Pei Zhen-xue took'Diagnosed by Western medicine and then discriminated by traditional Chinese medicine; TCM should be as the fundamental treatment method while Western medicine diagnosis as the supplemented way'as the guiding ideology. He fully utilized the modern medical diagnostic advantages to explore etiology and the nature of illness, so as to grasp the development and evolution rules of aplastic anemia. Furthermore, he organically combined the traditional Chinese medicine and Western medicine in clinical practice.'Diagnosed by Western medicine and discriminated by traditional Chinese medicine', which is a good method that help TCM to accurately grasp the evidence of a particular stage of the disease. It also can achieve a better clinical efficacy, and is the extension and development of traditional Chinese medicine diagnostics method.'TCM should be as the fundamental treatment method', which means TCM should be focused on the treatment of the disease, we must systematically consider both the TCM and Western medicine, so that the TCM theory and practice can be inherited.'Western medicine diagnosis as the supplemented way', which refers to that Western medicine has obvious advantages on a number of diseases, we have to use the complementary advantages of Western medicine.
     2. Clinical Research Results:According to the clinical observation, the total efficiency (relieved+improved) of the observation group treated by Western medicine was79.24%, which is significantly higher than that of the control group of60%. And there were significant differences between the two groups (P<0.05). The total efficiency (clinical cure+significant effect+effective) of the observation group treated by TCM was83.01%, which is also significantly higher than that of the control group of53.33%. And there were also significant differences between the two groups (P<0.05). Above all, the symptom score of the observation group treated by TCM is better than the control group (P<0.05). Before treatment, there are no significant differences on the peripheral blood (WBC, HB, PLT number) in the two groups (P>0.05). After treatment, the peripheral blood is increased in both the two groups, but, the observation group increased significantly higher than control group. Meanwhile, there are significant differences between the two groups (P<0.05). The bone marrow efficiency count also increased significantly after the treatment, and there are obvious differences between the two groups (P<0.05). In the observation group, CD+3and CD+4are improved while CD+8is reduced after treatment, there are obvious differences (P<0.05). In the control group, CD+3and CD+4are reduced while CD+8is improved, there also exists significant differences. Furthermore, there are no significant changes observed in the patients'liver function in both of the two groups after treatment, and there are no significant differences (P>0.05).
     Conclusion:The clinical study confirmed that the prescription contained dangchuanheji, stanozolol and cyclosporine A can effectively improve the chronic aplastic anemia. It can improve the clinical symptoms (mainly Chinese medicine symptom) and peripheral blood, bone marrow and regulate the immunity. Last but foremost, this prescription has no side effects on liver. It can significantly improve the quality of life of patients.
     This study suggests that the traditional Chinese medicine treatment mechanisms of chronic aplastic anemia are as follows:
     1:Tonifying kidney and strengthening spleen can promote bone marrow stem cell development.
     2:By adjusting blood T cell subsets, correcting T cell immune dysfunction, thereby lifting the suppression of bone marrow function, finally, therapeutic effect can be achieved.
     3:The bone marrow microenvironment can be improved by blood circulation.
     4:Detoxification can promote bone marrow.
     The author's innovation points and thinking on aplastic anemia:
     Firstly, by means of summarizing Professor Pei's medication features on treating aplastic anemia, the author draws the following conclusions:Detoxification can promote bone marrow to produce blood. Detoxification is not only the principles of treatment of aplastic anemia in patients with bleeding or bleeding tendency, but also can promote bone marrow of patients with aplastic anemia. Secondly, the judgment criterion on the efficacy of treatment should be combined with traditional Chinese medicine, which plays a vital role in improving the quality of life of patients. Therefore, the efficacy of treatment shouldn't be assessed only by the Western medicine standards.
     The author's thinking in the current study of aplastic anemia. First, aplastic anemia has special characteristics that are different from other'Consumption' syndrome, therefore, the pathogenesis foundation and differentiation system of the aplasitc anemia has its particularity. Second, in order to reveal the nature of symptoms of aplastic anemia, the material basis of aplastic anemia syndrome differentiation type and syndrome type need to be further studied. Furthermore, the symptoms of aplastic anemia should be determined by microscopic indicators for the purpose of well guiding clinical treatment and improving treatment efficacy. Third, the experimental method and clinical observation should be combined together in the research of aplastic anemia. On one hand, we have to explore objective and practical means of modeling. On the other hand, we should strengthen the clinical observational study. As a result, good reliability and repeatability of clinical efficacy can be obtained. Fourth, in the experimental level, the study of the efficacy mechanism of aplastic anemia in Chinese medicine must continue to learn from the latest research methods and ideas of Chinese medicine and modern medicine, such as molecular biology, apoptosis, cell cycle, protein expression, serum pharmacology and other aspects of the binding studies. Fifth, the combination of Western disease differentiation and TCM syndrome differentiation results in two different effects. Optimistically speaking, it can promote the progress of the clinical research of TCM. However, it can cause a certain adverse effect on individualized diagnosis and treatment. Sixth, currently, the traditional Chinese medicine only is only considered as a supplementary mean in the treatment, we haven't pay enough attention on the complementary between Western medicine and traditional Chinese medicine.
引文
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