“调肺”治疗儿童多发性抽动症医案数据挖掘研究及中药复方对小鼠免疫功能影响的研究

【作者】 李燕；

【导师】 徐荣谦；

【作者基本信息】 北京中医药大学 ， 中医儿科学， 2011， 博士

【摘要】 研究目的利用数据挖掘技术,对“调肺”治疗多发性抽动症的医案进行挖掘分析探索多发性抽动症的基本病因病机和本次研究“调肺”治疗本病的临证辨治思路,并尝试探求本病“调肺”治疗的部分理论意义。同时,应用实验的研究方法,观察“调肺”治疗多发性抽动症的中药复方对免疫低下小鼠免疫功能的影响,探索“调肺”复方可能对多发性抽动症免疫影响的作用机制。研究方法1.“调肺”治疗儿童多发性抽动症医案数据挖掘研究(1)按照纳入标准,确定纳入病例,共收集多发性抽动症病例98例,110例次医案。(2)按医案临床信息采集要点,收集记录临床信息资料。(3)应用“医案采集系统”及“中医处方智能分析系统信息采集界面”,对医案信息进行录入。利用《中医主题词表》对医案信息进行标引。(4)医案由专人录入,录入人员要经过专门培训。对录入后的病例进行多次核查。随机抽取病例进行检查,以确保录入质量。(5)应用中医医案数据库系统和中医处方智能分析系统,对医案进行挖掘分析。2.“调肺”治疗多发性抽动症中药复方对小鼠免疫功能影响的研究环磷酰胺50 mg·kg-1腹腔注射建立免疫功能低下小鼠模型,“调肺”治疗多发性抽动症中药复方(3,6,12 g·kg-1)灌胃给药连续7天,用碳粒廓清法观察小鼠单核巨噬细胞吞噬功能,耳肿增重法观察小鼠迟发型超敏反应,溶血素抗体测定法观察小鼠溶血素抗体生成。研究结果1.“调肺”治疗儿童多发性抽动症医案数据挖掘研究(1)利用“中医医案数据库系统”对多发性抽动症医案的研究①一般资料：多发性抽动症男性患儿比女性患儿多,男女之比为5.1：1；就诊年龄以6～15岁患儿居多,15岁后人数骤减。②多发性抽动症常见的症状体征有：红舌、脉弦滑、腻苔、眼肌抽动、喉中怪声、咽红、黄苔、眠差、鼻腔红、性急易怒、白苔、皱鼻、耸肩、手肌抽动、点头等。③医案所涉及的病因包括：内风、热痰、六淫、情志伤、风痰、外伤、食伤等,但主要以内生邪气为主。④医案涉及病位肝者为99.09%,心为13.64%,脾为4.55%,肺为3.64%。⑤医案所涉及的病机：肝风内动最显著81.82%,痰火扰心13.64%,痰火上扰13.64%,脾虚肝旺4.55%,风痰阻络0.91%。⑥医案所涉及的证候类型：肝风内动证81.82%,痰火上扰证13.64%,脾虚肝旺证4.55%。⑦医案所涉及的治疗方法以平熄内风,疏风化痰(81.82%)为主,同时应用清心安神、清热化痰、熄风涤痰、调和肝脾的方法。治法经完全分类统计后,多发性抽动症治疗以“治风”、“祛痰”为主,占所有治法的89.51%。⑧用药规律：“调肺”治疗多发性抽动症用药比较集中,苍耳子、伸筋草酸枣仁、木瓜、清半夏、辛夷、玄参、板蓝根、钩藤,是“调肺”治疗多发性抽动症最常用的中药。(2)利用“中医处方智能分析系统”对多发性抽动症医案的研究①处方药物使用权重较高的中药有：酸枣仁、木瓜、伸筋草、清半夏辛夷、乌梢蛇、钩藤、白芍、蕤仁、蝉蜕、炙甘草、天麻等。②处方药物药性以平性、温性、微寒较高；110例次处方,几乎整体偏凉(95.45%)。③处方药物药味以甘、苦、辛为主④处方药物归经以归肝为主,其次肺、胃、脾、心,再一级别为肾、其他。⑤对处方功效权重计算,功效祛风、安神、清热、活络、平肝、解疮毒、熄风、明目、散结、舒筋居前10位；经筛选后的前10位功效由高到低依次为：清热、祛风、平肝、活络、散结、祛痰、熄风、舒筋、祛湿、泻火⑥对处方涉及证素进行计算,证素风邪、神不安、热、络脉阻、肝亢疮毒、热毒、筋急、目、动风居前10位；经筛选后热、风邪、肝亢、络脉阻、结、痰、动风、筋急、湿、实火居前10位。⑦处方主要适应证居前10位的由高到低依次为：肝风内动证、风湿化热证、痰热动风证、表寒里热证、热盛动风证、湿热蕴结证、风中经络证、痰热内扰证、胃肠湿热证、风热化火证。⑧对处方症状体征关注度进行计算,其中前10位症状体征中,除去主症(眼肌抽动、皱鼻、耸肩、手肌抽动)、舌(红舌、黄苔)、脉(脉弦滑),伴随症状(性急易怒、眠差),咽红的关注度较高。2.“调肺”治疗多发性抽动症中药复方对小鼠免疫功能影响的研究(1)对环磷酰胺免疫抑制小鼠单核巨噬细胞吞噬功能的影响“调肺”复方高剂量组、中剂量组能明显提高免疫低下小鼠的碳粒廓清指数K和吞噬指数α(P<0.01,P<0.05),提示“调肺”复方能提高环磷酰胺免疫抑制小鼠的单核巨噬细胞吞噬功能。(2)对环磷酰胺免疫抑制小鼠迟发型过敏反应(DTH)的影响“调肺”复方高剂量组、中剂量组可拮抗环磷酰胺诱导的免疫低下小鼠耳肿胀度减轻(P<0.01,P<0.05),增强低下的迟发型超敏反应(DTH)反应水平。(3)对环磷酰胺免疫抑制小鼠血清溶血素含量的影响‘调肺”复方高剂量组能提高免疫低下小鼠血清溶血素含量(P<0.05)。研究结论1.通过对医案中症状体征、病因、病位、病机、证候、治法及处方用药进行挖掘分析,客观、详细地分析总结了本病的基本病因病机,病因包括感受外邪、情志内伤、饮食因素、外伤因素、胎遗胎传及先天不足；病位主要在肝,但与肺、脾、心、肾相关；风、火、痰既是本病的致病因素,又是病理产物,是影响疾病转归的重要因素,病程中风、火、痰相互作用导致了本病的发生或加重。2.本次研究“调肺”治疗多发性抽动症临证辨治过程中,注重肝肺并调,内外并治。“祛风、调肝、清热”是本次研究“调肺”治疗本病把握的核心,在处方用药性味归经及功效等的侧重应用上都有体现,同时又注意把握全方“祛风清热,平肝祛痰、安神”的综合作用。临证过程中也非常注意观察患儿鼻咽部的变化对本病的影响。3.肺与肝在生理病理上存在密切的联系,多发性抽动症病变核心在肝,调肺对本病同样也起到治疗作用；肺邪传肝是本病发病极为重要的潜在因素,调肺截断外邪内传的通路,对于多发性抽动症治疗具有积极意义；痰是威胁多发性抽动症的重要病邪,“调肺”可改善机体水液的代谢的异常,减少内生痰邪的产生,有利于多发性抽动症的治疗4.“调肺”治疗多发性抽动症中药复方通过增强非特异性免疫、细胞免疫、体液免疫功能,可以减少机体对链球菌、病毒等致病微生物感染的机会,有利于神经-内分泌-免疫网络的稳定,从而减轻或消除抽动症状。5.“正气”可以类推为现代医学的“免疫力”,正气是决定疾病发生发展的决定性因素,其生成、输布运行均与肺具有密切的联系,“调肺”治疗本病同免疫调节治疗方法内涵具有部分近似性。6.本研究从医案中医临证要素出发,引入数据挖掘技术,初步探索了本病病因病机和“调肺”治疗的临证辨治思路,验证了数据挖掘的方法在中医医案研究分析中的可行性。更多还原

【Abstract】 4“调肺”治疗儿童多发性抽动症医案数据挖掘研究及中药复方对小鼠免疫功能影响的研究ABSTRACTObjective By analyzing the Tourette’s syndrome cases based on data mining,explore the basic cause and mechanism of Tourette’s syndrome withtreatment by regulating lung. And try to discuss the theoreticalsignificance of TS treatment by regulating lung. Meanwhile, study theeffect and explore the possible mechanism of "Regulating lungs’composite prescription on immunity effects in immunodepressed mice withTS.Methods 1. The study of Tourette’s syndrome cases with treatment of regulatingthe lung based on date mining (1)Collected 110 cases of patients according to diagnosis andclassification standards Tourette’s syndrome. (2)Collected and recorded clinical information according to medicalrecord. (3)Input information and established a database of Tourette’ssyndrome. Data preprocessing, including data standardization andquantification for data indexing. (4)Multiple post-entry verifications.10% of randomly selected caseswere checked to ensure the quality of entry. (5)Analyzed the Tourette’s case with "CPDBS" and "CPIAS" 2. Research of the effect of "Tiaofei" composite prescription onimmunity effects in immunodepressed mice The immunodepressed mice models were induced by intraperitonealinjection of cyclophosphamide with 50mg·kg-1. Mice were administratedwith "Tiaofei" composite prescription 3,6,12 g·kg-1 for 7 consecutivedays. The phagocytic activity of monocytes, the delayedhypersensitivity reaction and the haemolysin antibody formation in micewere observed by means of carbon particle clearance, ear swelling andhaemolysin antibodies.Results 1. The study of Tourette’s syndrome cases with treatment ofregulating the lung based on data mining (1)The study of Tourette’s syndrome cases with "CPDBS"①General information:Tourette’s syndrome Incidence rate of boyis higher than girl, the ratio is 5.1:1. Majority in age of 6-15 years old, the incidence rate significantly decreased after age of 15.②Common clinical symptoms of Tourette’s syndrome include:redness of tongue, wiry and slippery pulse, greasy tongue, movement tics, vocal tic, redness of pharynx, insomnia, etc.③The causes of Tourette’s syndrome included in this research: endogenous wind, heat-phlegm, internal injury caused by excess of emotions, surgical trauma, dyspepsia. But the main cause is endogenous factor which affecting health.④Tourette’s syndrome mainly damages liver, counted for 99.09%; heart, counted for 13.64%; spleen, counted for 4.55%; lung, counted for 13.64%.⑤The mechanisms of Tourette’s syndrome include:endogenous liver wind, counted for 81.82%; pyrophlegmatic mania,13.64%; splenic asthenia and hepatic accentuation,4.55%; obstruction of collateral caused by wind-phlegm,0.91%.⑥The cases of Tourette’s syndrome involved three complex symptoms:endogenous liver wind,81.82%; pyrophlegmatic mania,13.64%; splenic asthenia and hepatic accentuation,4.55%.⑦The treatment of Tourette’s syndrome in this research includes calming the liver to stop the wind, expelling wind and dissipating phlegm mainly(counted for 81.82%), easing mental anxiety, eliminating phlegm by cooling, stopping endogenous wind and washing away the phlegm, eliminating phlegm by cooling coordinating. After the complete classification of Statistics, the treatment mainly include calming wind and eliminating phlegm, counted for 89.51%.⑧The most common herbs of Tourette’s syndrome prescription include in this reach:siberian cocklebur fruit, lycopodii herba, jujube seed, Chinese quince, prepared RHIZOMA PINELLIZE, biond magnolia flower, figwort root, isatis root, gambir plant.(2)The study of Tourette’s syndrome cases with "CPIAS"①Herbs used in the Tourette’s syndrome prescriptions include: jujube seed, Chinese quince, lycopodii herba, prepared RHIZOMA PINELLIZE, biond magnolia flower, black snake, gambir plant, paeoniae alba, nux prinsepiae, cicada slough, prepared RADIX GLYCYRRHIZAE, tall gastrodia tuber, etc.②The property of the herbs of Tourette’s syndrome prescriptions mainly is mild, warm and cool.③The flavor of the herbs of Tourette’s syndrome prescriptions mainly is sweet, bitter and pungent.④Meridian distribution of herbs show up that the maximum distribution percentage is the liver system, followed by the lung system, spleen system, heart system, kidney system, and else.⑤The effectiveness of Tourette’s syndrome prescription in this research mainly include:eliminating wind, calming the nerves, heat-clearing, activating collaterals, calming the liver, eliminating sore poison, stopping endogenous wind, improving acuity of vision, eliminating stagnation, relaxing the tendons, which are among the top 10. After screening, the effectiveness of the top 10 in order were heat-clearing, eliminating wind, calming the liver, activating the tendons, eliminating stagnation, eliminating phlegm, stopping endogenous wind, relaxxing the tendons, dehygrosis, purging pathogenic fire.⑥Syndrome elements of Tourette’s syndrome prescriptions involved in this research mainly include:pathogenic wind, anxiousness, pathogenic heat, collaterals and subcollateral s blockage, hepatic accentuation, sore poison, pyretic toxicity, muscular contracture, eye, wind symptom, which are among the top 10. After screening effectiveness of the top 10 in order were pathogenic heat, pathogenic wind, hepatic accentuation, collaterals and subcollateral s blockage, stagnation, phlegm, wind symptom, muscular contracture, dampness, distinguish fire.⑦These are ten kinds of complex symptom of Tourette’s syndrome prescriptions in this research by order:endogenous liver wind, wind and dampness heated, convulsion caused by heat-phlegm, external cold and internal heat, endogenous wind-evil caused by excessive heat, blockage caused by humid heat, veins and arteries invasion by wind, disturbance caused by phlegm-heat attacking, humid heat caused by stomach intestine blockage, fire-syndrome resulting from wind-heat.⑧Signs and symptoms in this research are focused on movement tic, creasing nose, shrugging shoulders, vocal tic, redness of tongue, yellow fur, wiry and slippery pulse, restless and angry, sleep week, redness of pharynx, which were the the top 10. Redness of pharynx is more significant in the treatment of Tourette’s syndrome.2. Research of the effect of "Tiaofei" composite prescription on immunity effects in immunodepressed mice.6 and 12 g·kg-1 dose of "Tiaofei" composite prescription could improve clearance index and phagocytic index in immune function of carbon of mice, decrease ear swelling induced by cyclophosphamide.12 g·kg-1 dose of "Tiaofei" composite prescription could increase content of haemolysin antibody induced by cyclophosphamide.Conclusion1. Through s i gns and symptoms, etiology, disease bits, pa thogenes i s, therapy and prescription medication of medical records, objectively and detailedly analyze the summary of the basic etiology and pathogenesis of the disease. Causes included:affected by evil qi,emotions injuries, dietary factors, trauma factors, genetic, and congenital deficiency. Main problem is located in the Liver, but related with lung, spleen, heart and kidney. Wind, fire, phlegm were the main cause in this disease, and also are pathological products. They also are important factors course of this disease, which worsening of the disease.2. Regulating both inside and outside of the liver and lung are important in this treatment process. In this study, "expelling wind" "harmonizing liver", "removing heat " are the core treatment of the regulating lung therapy. In addition to reflect application of prescription,medication, taste, tropism and effect, also concentrate to the combined effects with all parties of expelling wind, remove heat, harmonizing liver, removing sputum and calm the nerves. In the clinical process, concentrate on the changes in children with nasopharyngeal impact of this disease.3. According TCM, lung and liver have a close link on the physiological and pathological part. Main problem of Tourette’s syndrome is in liver, regulating lung also play a therapeutic role. Evil qi turn from Lung to liver is very important factor of this disease. Therefore, regulating lung, has positive effect for Tourette’s syndrome. Sputum is also an important pathogenic factor of threatening Tourette Syndrome. Through the "regulating lung" can improve the body’s abnormal fluid metabolism, while reducing endogenous sputum evil, which are conducive to the treatment of Tourette’s syndrome.4. In treating Tourette’s syndrome, the regulating lung composite prescription can enhance non-specific immunity, cellular immunity, humoral immunity, largely reduce streptococcus, viruses and other pathogenic microorganisms infection. Meanwhile, it can play a role in correcting functional status of the disorder with Tourette Syndrome cytokines. It also can induce different cytokine to achieve the homeostasis of physiological. Thus it can stabilize neuro- endocrine -immune network and or reduce the tic symptoms.5. "Zhengqi" can be regarded as immunity in modern medicine. It is decisive factor in the development of disease. The generation, transmission and distribution, whole operation of "zhengqi’ are closely linked with lung. Therefore, the "regulating lung" treatment of Tourette’s syndrome has some similar meaning with immunomodulatory therapy.6.This study used clinical factors of medical records as starting point, by means of data mining techniques, preliminarily explore of etiology and pathogenesis with regulating lung as clinical treatment point. And verify the feasibility of data mining methods in the study about medical records of Traditional Chinese Medicine.更多还原