半佛纳米微丸治疗癔球症的临床及基础研究
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摘要
癔球症是临床上常见的胃肠功能性疾病。主要表现为精神神经症状及咽部异物感,病情反复,缠绵难愈,给患者的工作、生活都有较大的影响。目前对本病发病机理和治疗的理想药物研究尚不够深入。临床上半夏厚朴汤对治疗癔球症有较好的疗效。半佛纳米微丸是在半夏厚朴汤方加减后,以纳米技术为依托所研制的一种中药新剂型。为了进一步研究半佛纳米微丸对癔球症的作用机理,本课题在江苏省科技厅医药高技术(三药)项目“半佛纳米微丸的新药临床前研究”(编号BG2006606)的资助下采用了临床采集病例研究及慢性咽炎动物模型和慢性抑郁动物模型相结合的方法来研究半佛纳米微丸治疗癔球症的作用机理。
一、临床研究
【目的】通过相关患者临床资料的回顾性分析,探讨癔球症中医证候分布规律及发病机制。
【方法】采用现场调查方式,让调查对象填写调查问卷,以国内外公认诊断标准,构建证候四诊合参数据库,并用spss10.0统计软件分析。
【结果】癔球症证候的分布与肝最为密切,占83.1%,其次为脾,占12.1%。
【结论】癔球症的病因及诱发因素与精神因素、季节、饮食及劳逸等关系密切相关;病位主要在肝、脾;病机关键是肝郁。
二、慢性咽炎动物模型:
【目的】研究半佛纳米微丸对慢性咽炎动物模型有关基础指标、血液流变学、咽部病理形态学的影响。【方法】将实验兔随机分为空白组、模型组、阳性药物组、半佛纳米微丸低、中、高剂量组,采用氨水和松节油复合因素在日本大耳白兔咽部直接造模制作慢性咽炎动物模型,定期观察慢性咽炎兔体重、肛温及表现,并抽取实验兔耳缘静脉血进行测定,判断疗效。实验结束后,取实验兔咽部组织进行HE染色,观察病理变化,并使用spss10.0分析软件对数据进行分析。
【结果】半佛纳米微丸能够减少动物外周血象中慢性炎细胞(淋巴细胞、单核细胞)的数量,减少咽部血管通透性及炎细胞渗出,抑制纤维组织增生,能够改善血液流变学,增强免疫功能。
【结论】表明半佛纳米微丸对慢性咽炎动物模型的治疗作用是通过抗炎、改善血液流变性、增强免疫等多途径、多环节发挥作用来实现的。
三、慢性抑郁动物模型:
【目的】研究半佛纳米微丸对慢性抑郁动物模型行为学及大鼠脑内单胺类神经递质的影响。
【方法】将SD大鼠随机分为空白组、模型组、阳性药物组、半佛纳米微丸低、中、高剂量组,采用慢性不可预知应激(24 h断水、用止血钳夹尾部1 min、污染鼠笼、4℃冰水游泳3 min、24 h黑白颠倒、24 h断食、水平震荡)建立大鼠慢性抑郁模型,定期进行开野行为观察(open-field tests),观察半佛纳米微丸对慢性抑郁大鼠的行为学影响。实验结束后,取大鼠脑组织,经高效液相测定不同分组大鼠单胺类神经递质含量,并用spss10.0分析软件对数据进行分析。
【结果】半佛纳米微丸对抑郁大鼠的体重、水平运动、垂直运动均有改善。并且能够升高5-HT、DA含量,进而改善大鼠行为特征。
【结论】表明通过调节5-HT、DA神经递质是半佛纳米微丸抗抑郁机制之一。
Globus hystericus is the frequently-occurring disease of stomach intestine functional disease.It unconsciously presents as psychiatrical and neurological symptoms and globus sensation with patients’condition waving,lingering and difficult to cure.It has a bad influence on work and life of amplitude patients.At present,the study on its pathogenesis and ideal treatment is insufficient. Now Pinellia and Magnolia Bark Decoction has obtained a good effect on globus hystericus.And BanFo Nanometer Micro-Pill which is based on Pinellia and Magnolia Bark Decoction product with the new nanotechnology. For further study and trying to find out the mechanism of globus hystericus interfered by BanFo Nanometer Micro-Pill,the study whcih is subsidized by Jiangsu Scinence And Technology Department collect the clinical cases and built the animal model with chronic pharyngitis by using ammonia and turpentine to the pharyngeal part of the rabbit and the animal depression model by exposing to an unpredictanle sequence of stressors to the rat. Clinical research
【Objective】investigated the distribution rule and the pathogenesis of the characteristics of traditional Chinese medical syndrome in Globus hystericus by the retrospective analysis of the patient
【Methos】use the approch of cross-sectional study,adopt the on-the-spot investigation method,let respondents fill in the Globus hystericus questionnaire,combine the clinical examination results,gather the respondent's information material of the four diagnosis methods of the traditional Chinese medicine through doctor's interview at the same time and carry on differentiation of symptoms and signs according to the relevant syndroms standard of Chinese medicine.Then,collect the information of the qualified questionnaires and enter database,use SPSS10.0 software to study the relevant influence factor,the distribution of the Chinese medicine syndromes and the characteristic of Globus hystericus.
【Results】the distribution of the Chinese medicine syndromes and the characteristic of Globus hystericus was that the Chinese medicine syndromes of Globus hystericus correlate to gan,pi;which respectively accounted to 83.1%,12.1%.
【Conclusion】The inducements of Globus hystericus are relevant to the sentiment,season,diet and fatigue.its main places of disease is gan,pi.And the key of pathogenesis is liver depression. The animal model with chronic pharyngitis:
【Objective】To explor the influence of Globus hystericus interfered by BanFo Nanometer Micro-Pill which chose the following figures as the blood rheology, the pharyngeal part pathologic morphology and some basic figures of the chronic pharyngitis.
【Methos】To divide randomly rabbit into 6 groups, the normal control group (NS), the chronic pharyngitis model group,the positive group (Man Yan Shu Ning), BanFo Nanometer Micro-Pill in low, medium, high dosage, there were 8 rabbits in each group. the study built the animal model with chronic pharyngitis by using ammonia and turpentine to the pharyngeal part of the rabbit. Regularly observed the weight,rectal temperature and behavior of the rabbit,and inspected the blood of the rabbit.At the end of the study,observed the pharyngeal part pathologic morphology of the rabbit.
【Results】BanFo Nanometer Micro-Pill can reduce the quantity of the chronic inflammatory cells (lymphocyte, monocyte) in the animal blood, alleviate permeability of the blood vessel walls of the pharyngeal department and exfiltration of inflammatory cells, and repress proliferation of the fibrous tissue,and can improve the blood rheology, strengthen the immune function.
【Conclusion】the results of the research showed that the remedial functions of BanFo Nanometer Micro-Pill were realized by many paths, such as anti一inflammation, improvement permeability of pharyngeal department blood vessel, alleviate the inflammation exfiltration, inhibition fiber proliferation, improvement the blood rheology, strengthen immunity etc.
The animal depression model:
【Objective】To investigate the effect of BanFo Nanometer Micro-Pill on the behaviors of depressed animal and detect the amount of monoamine neurotransmitte in brain of rats. To approach preliminary the antidepressant mechanism of mechanism of BanFo Nanometer Micro-Pill.
【Methods】To divide randomly adult Sprague-Dawley (SD) rats into 6 groups, the normal control group (NS), the depression model group, the positive group (Fluoxetine), BanFo Nanometer Micro-Pill in low, medium, high dosage, there were 12 rats in each group. All rats were administered medicine by intragastric administration. Model. Isolated-living condition and chronic mild unpredictable stress with being bred in a single cage are applied successively to set up the rat depression model except normal control group, that it is using seven different stressors (the reverse of day and night, the swimming in ice water, shaking, clamping the tail,the prohibition against water, abrosia, polluting the cage). Regularly observing the behavior of the rats by the open-field tests.At the end of the study,detecting the amount of monoamine neurotransmitte in brain of rats.
【Results】BanFo Nanometer Micro-Pill can improve obviously behavioral index and show curative and preventative effect to the animal depression model,and it also can increase obviously the amount of monoamine neurotransmitter (NE, 5-HT, 5-HIAA) in the animal depression model, which may be one of the mechanisms of its anti-depressive action.
一、临床研究
【目的】通过相关患者临床资料的回顾性分析,探讨癔球症中医证候分布规律及发病机制。
【方法】采用现场调查方式,让调查对象填写调查问卷,以国内外公认诊断标准,构建证候四诊合参数据库,并用spss10.0统计软件分析。
【结果】癔球症证候的分布与肝最为密切,占83.1%,其次为脾,占12.1%。
【结论】癔球症的病因及诱发因素与精神因素、季节、饮食及劳逸等关系密切相关;病位主要在肝、脾;病机关键是肝郁。
二、慢性咽炎动物模型:
【目的】研究半佛纳米微丸对慢性咽炎动物模型有关基础指标、血液流变学、咽部病理形态学的影响。【方法】将实验兔随机分为空白组、模型组、阳性药物组、半佛纳米微丸低、中、高剂量组,采用氨水和松节油复合因素在日本大耳白兔咽部直接造模制作慢性咽炎动物模型,定期观察慢性咽炎兔体重、肛温及表现,并抽取实验兔耳缘静脉血进行测定,判断疗效。实验结束后,取实验兔咽部组织进行HE染色,观察病理变化,并使用spss10.0分析软件对数据进行分析。
【结果】半佛纳米微丸能够减少动物外周血象中慢性炎细胞(淋巴细胞、单核细胞)的数量,减少咽部血管通透性及炎细胞渗出,抑制纤维组织增生,能够改善血液流变学,增强免疫功能。
【结论】表明半佛纳米微丸对慢性咽炎动物模型的治疗作用是通过抗炎、改善血液流变性、增强免疫等多途径、多环节发挥作用来实现的。
三、慢性抑郁动物模型:
【目的】研究半佛纳米微丸对慢性抑郁动物模型行为学及大鼠脑内单胺类神经递质的影响。
【方法】将SD大鼠随机分为空白组、模型组、阳性药物组、半佛纳米微丸低、中、高剂量组,采用慢性不可预知应激(24 h断水、用止血钳夹尾部1 min、污染鼠笼、4℃冰水游泳3 min、24 h黑白颠倒、24 h断食、水平震荡)建立大鼠慢性抑郁模型,定期进行开野行为观察(open-field tests),观察半佛纳米微丸对慢性抑郁大鼠的行为学影响。实验结束后,取大鼠脑组织,经高效液相测定不同分组大鼠单胺类神经递质含量,并用spss10.0分析软件对数据进行分析。
【结果】半佛纳米微丸对抑郁大鼠的体重、水平运动、垂直运动均有改善。并且能够升高5-HT、DA含量,进而改善大鼠行为特征。
【结论】表明通过调节5-HT、DA神经递质是半佛纳米微丸抗抑郁机制之一。
Globus hystericus is the frequently-occurring disease of stomach intestine functional disease.It unconsciously presents as psychiatrical and neurological symptoms and globus sensation with patients’condition waving,lingering and difficult to cure.It has a bad influence on work and life of amplitude patients.At present,the study on its pathogenesis and ideal treatment is insufficient. Now Pinellia and Magnolia Bark Decoction has obtained a good effect on globus hystericus.And BanFo Nanometer Micro-Pill which is based on Pinellia and Magnolia Bark Decoction product with the new nanotechnology. For further study and trying to find out the mechanism of globus hystericus interfered by BanFo Nanometer Micro-Pill,the study whcih is subsidized by Jiangsu Scinence And Technology Department collect the clinical cases and built the animal model with chronic pharyngitis by using ammonia and turpentine to the pharyngeal part of the rabbit and the animal depression model by exposing to an unpredictanle sequence of stressors to the rat. Clinical research
【Objective】investigated the distribution rule and the pathogenesis of the characteristics of traditional Chinese medical syndrome in Globus hystericus by the retrospective analysis of the patient
【Methos】use the approch of cross-sectional study,adopt the on-the-spot investigation method,let respondents fill in the Globus hystericus questionnaire,combine the clinical examination results,gather the respondent's information material of the four diagnosis methods of the traditional Chinese medicine through doctor's interview at the same time and carry on differentiation of symptoms and signs according to the relevant syndroms standard of Chinese medicine.Then,collect the information of the qualified questionnaires and enter database,use SPSS10.0 software to study the relevant influence factor,the distribution of the Chinese medicine syndromes and the characteristic of Globus hystericus.
【Results】the distribution of the Chinese medicine syndromes and the characteristic of Globus hystericus was that the Chinese medicine syndromes of Globus hystericus correlate to gan,pi;which respectively accounted to 83.1%,12.1%.
【Conclusion】The inducements of Globus hystericus are relevant to the sentiment,season,diet and fatigue.its main places of disease is gan,pi.And the key of pathogenesis is liver depression. The animal model with chronic pharyngitis:
【Objective】To explor the influence of Globus hystericus interfered by BanFo Nanometer Micro-Pill which chose the following figures as the blood rheology, the pharyngeal part pathologic morphology and some basic figures of the chronic pharyngitis.
【Methos】To divide randomly rabbit into 6 groups, the normal control group (NS), the chronic pharyngitis model group,the positive group (Man Yan Shu Ning), BanFo Nanometer Micro-Pill in low, medium, high dosage, there were 8 rabbits in each group. the study built the animal model with chronic pharyngitis by using ammonia and turpentine to the pharyngeal part of the rabbit. Regularly observed the weight,rectal temperature and behavior of the rabbit,and inspected the blood of the rabbit.At the end of the study,observed the pharyngeal part pathologic morphology of the rabbit.
【Results】BanFo Nanometer Micro-Pill can reduce the quantity of the chronic inflammatory cells (lymphocyte, monocyte) in the animal blood, alleviate permeability of the blood vessel walls of the pharyngeal department and exfiltration of inflammatory cells, and repress proliferation of the fibrous tissue,and can improve the blood rheology, strengthen the immune function.
【Conclusion】the results of the research showed that the remedial functions of BanFo Nanometer Micro-Pill were realized by many paths, such as anti一inflammation, improvement permeability of pharyngeal department blood vessel, alleviate the inflammation exfiltration, inhibition fiber proliferation, improvement the blood rheology, strengthen immunity etc.
The animal depression model:
【Objective】To investigate the effect of BanFo Nanometer Micro-Pill on the behaviors of depressed animal and detect the amount of monoamine neurotransmitte in brain of rats. To approach preliminary the antidepressant mechanism of mechanism of BanFo Nanometer Micro-Pill.
【Methods】To divide randomly adult Sprague-Dawley (SD) rats into 6 groups, the normal control group (NS), the depression model group, the positive group (Fluoxetine), BanFo Nanometer Micro-Pill in low, medium, high dosage, there were 12 rats in each group. All rats were administered medicine by intragastric administration. Model. Isolated-living condition and chronic mild unpredictable stress with being bred in a single cage are applied successively to set up the rat depression model except normal control group, that it is using seven different stressors (the reverse of day and night, the swimming in ice water, shaking, clamping the tail,the prohibition against water, abrosia, polluting the cage). Regularly observing the behavior of the rats by the open-field tests.At the end of the study,detecting the amount of monoamine neurotransmitte in brain of rats.
【Results】BanFo Nanometer Micro-Pill can improve obviously behavioral index and show curative and preventative effect to the animal depression model,and it also can increase obviously the amount of monoamine neurotransmitter (NE, 5-HT, 5-HIAA) in the animal depression model, which may be one of the mechanisms of its anti-depressive action.
引文
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[1]贺石林.中医科研设计与统计方法,长沙:湖南科技出版社.1989.88.
[2]李仪奎.中药药理实验方法学.上海:上海科学技术出版社.1991,300.
[3]苗明三.实验动物和动物实验技术.北京:中国中医药出版社.1997,143.
[4]陈奇.中药药理实验方法.北京:人民卫生出版社.1994,23.
[5]周立国.药物毒理学.北京:中国中医药科技出版社. 2003,146-159.
[6]徐叔云,卞如濂,陈修.北京:人民卫生出版社. 2002.231.
[7]沈峰,陈国丰,曹济航.中西医结合治疗咽异感症70例疗效观察[J].中国中西医结合耳鼻喉科杂志,2004,12(4):215.