超微定喘方治疗哮喘热哮证的临床观察及对哮喘大鼠神经源性炎症的影响
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摘要
目的：比较超微定喘方不同剂量对哮喘模型大鼠的肺内免疫、神经源性气道炎症的影响,探讨其疗效机理,并探寻其有效剂量。观察超微定喘方对成人与儿童哮喘(热哮证)的临床疗效,并检测患者治疗前后肺功能的变化,为其临床应用提供依据。
方法：①健康Sprapue-Demey大鼠随机分为正常对照组(A组)、哮喘模型组(B组)、定喘汤汤剂组(C组)、超微定喘方低剂量组(D组)、超微定喘方等剂量组(E组)。建立卵白蛋白哮喘模型,通过气道反应性测定确保模型成功。D、E组分别予定喘汤超微配方颗粒等倍剂量、1/2剂量治疗。观察NGF(Nerve growth factor)、SP (Substance P)及其mRNA (messenger Ribonucleic acid)在模型大鼠肺组织中的表达,并用显微图像分析系统测定数个视野中的阳性系数和灰度值。②采用随机方法将成人与儿童哮喘患者各90例分别分为3组,对照组给予氨茶碱加布地奈德治疗,定喘汤组在对照组基础上加定喘汤汤剂治疗,超微定喘方组在对照组基础上加超微定喘方治疗。检测治疗前后EOS (eosinophil)、IL-4(Interleukin4)及肺功能水平。
结果：五组大鼠的基础呼吸阻力(Re)相似,予生理盐水激发后的Re也相似,均无统计学意义(P>0.05)。予10～40ug/kg浓度梯度的Ach (acetylcholine)激发后,哮喘模型组Re比较正常对照组,差异有统计学意义(P<0.05)。80～160ug／kg浓度梯度的Ach激发后,哮喘模型组Re显著增加(P<0.01)。等剂量组与低剂量组之间无差异(P>0.05)。模型组的NGF、SP含量明显升高,模型组与其余组之间差异显著(P<0.01),等剂量组与低剂量组、正常组之间无差异(P>0.05)。定喘汤汤剂组、等剂量组、低剂量组大鼠肺组织NGF、NGFmRNA平均阳性系数低于模型组,差异有统计学意义(P<0.01)。
成人哮喘的临床研究显示,定喘汤组的总有效率与西医对照组相比无统计学差异,说明二者的临床疗效相近(P>0.05)。在平喘及缓解哮鸣音方面,各组比较无显著性差异(均P>0.05)。在改善咳嗽及咯痰症状方面,三者有统计学上的差异(P<0.05),定喘汤及超微定喘方优于西医对照组。在精神、口渴、食欲、舌苔脉象方面,三者比较无显著性差异(均P>0.05)。在改善发热、面色、大小便等症状方面,三者有统计学上的差异(P<0.05),定喘汤及超微定喘方优于西医对照组。疗程后三组第1秒用力呼气量及最大呼气流速较治疗前都有所提高(P<0.05),定喘汤及超微定喘方组与西医对照组治疗效果相比无统计学差异(P>0.05)。疗程后三组均能显著降低哮喘时外周血中异常升高的EOS数,统计学有显著性差异(P<0.01),定喘汤及超微定喘方组与西医对照组相比无统计学差异(P>0.05)。疗程后三组均能显著降低哮喘患者血清IL-4水平,统计学有显著性差异(P<0.01),定喘汤及超微定喘方组与西医对照组相比有统计学差异(P<0.05)。
儿童哮喘的临床研究显示,各组总有效率比较,差异无明显统计学意义(P>0.05),而临床控制率比较,治疗组明显高于对照组,差异有统计学意义(P<0.05),各组治疗前后主要症状积分、总积分比较有显著差异,对照组除对紫绀外,其他症状的前后积分、总积分比较也有显著差异。各组对症状改善经差值比较(成组t检验),咳嗽、咯痰痰鸣、鼻煽、哮呜音比较无差异(P>0.05)；定喘汤饮片组及超微定喘方组在改善喘息、紫绀症状方面优于对照组(P<0.05)。定喘汤组、超微定喘方组治疗前后次要症状积分、总积分比较均有显著差异,对照组除发热面色外,其他症状的前后积分、总积分比较也有显著差异。各组对症状改善经差值比较,精神、口渴、食欲、舌苔脉象比较无差异(P>0.05)；发热、面色、大小便比较有差异(P<0.05)。定喘汤组、超微定喘方组治优于对照组。疗程后各组第1秒用力呼气量及最大呼气流速较治疗前都有明显增加(P<0.05),说明都能改善肺功能。在改善肺功能方面,定喘汤饮片组及超微定喘方组优于西医对照组(P<0.05)。
结论：①大鼠致敏哮喘模型形成后气道炎症反应明显,具有操作简单易行,造模成功率较高的优点。②致敏大鼠哮喘模型肺内NGF、SP含量增多。气道粘膜、粘膜下层、平滑肌层及肺间质炎症细胞胞浆内均有明显的NGF的定位表达,同时也可平行地观察到上述部位显著的NGFmRNA水平表达增高。③定喘汤及其超微制剂可以减轻哮喘模型大鼠肺内NGFmRNA水平的表达及NGF蛋白水平,表明其对气道神经源性炎症有改善作用。④超微定喘方以1/2等效剂量时即可达与传统汤剂相同的作用效果,其有良好的止咳化痰、平喘作用,能显著改善肺功能,降低哮喘时外周血中异常升高的嗜酸性粒细胞,下调IL-4,作用优予西医对照组。⑤超微定喘方在平喘及缓解哮鸣音方面与对照组作用相当。在改善咳嗽及咯痰症状方面,定喘汤及超微定喘方优于西医对照组,说明定喘汤和超微定喘方均有较好的平喘、止咳化痰作用。⑥超微定喘方在治疗儿童热性哮喘中,对其喘息、紫绀以及发热、面色、大小便等症状的改善较定喘汤更为明显,而在其他症状改善方面无明显差异。总疗效统计中,明显优于西医对照组。⑦超微定喘方治疗热哮证具有较好的临床疗效,并具有良好的安全性。
Objective:
To compare effect of different doses of supermicro DingChuan Decoction on pulmonary immune neurogenic airway inflammation of thermal asthma model rats, to investigate the curative mechanism, to explore effective dose. To observe clinical effect of supermicro DingChuan Decoction on adult and childhood asthma(thermal asthma),and to detect lung function changes of patients before and after treatment,to provide evidence for its clinical application.
Methods:
①health Sprapue-Demey rats are randomly divided into normal control group (group A), asthma model group (group B), DingChuan Decoction group (group C), low-dose supermicro DingChuan Decoction group (group D), supermicro DingChuan Decoction normal dose group (group E). To make ovalbumin asthma model with airway responsiveness determination to ensure successful.Group D and E are respectively to given supermicro DingChuan soup1/2dose and normal dose. To Observe NGF and SP and its mRNA expression in lung tissue of the rat models,and to determinate several positive coefficient and grey value of vision with microscopic image analysis system.
②andomly90cases of adult and90cases childhood asthma patients are separately divided into3groups, control group are given aminophylline and budesonide therapy, besides the drugs DingChuan Decoction group are given DingChuan Decoction, supermicro DingChuan Decoction group are given supermicro DingChuan Decoction.To detecte EOS, IL-4and lung function level.before and after treatment.
Results:
The basic respiratory resistance (Re) of the five groups rats are similar both before and after with physiological saline stimulated,there is no statistical significance (P>0.05). After given10-40ug/kg of Ach excitation, the difference of asthma model group and normal control group is statistically significant (P<0.05). After given80-160ug/kg of Ach excitation, Re of asthma model group increased significantly (P<0.01). There is no difference between normal dose group and low dose group (P>0.05). NGF> SP of model group increased, the difference between model group and other groups is significant (P<0.01), there is no difference between the dose group, low dose groupand normal control group (P>0.05). average positive coefficient of NGF、NGFmRNA of lung tissue of Dingchuan Decoction group, normal dose group, low dose group rats is lower than that in the model group, the difference is statistically significant (P<0.01).
Clinical study of adult asthma shows, the difference of total efficiency between Dingchuan Decoction group and the western medicine control group have no statistical difference, which shows the two have similar clinical curative effect(P>0.05). In relieving asthma and wheeze, there is no significant difference between groups (P>0.05). In the improvement of cough and expectoration symptom, there is significant difference (P<0.05), Dingchuan Decoction and supermicro Dingchuan decoction is better than western medicine control group. In spirit, appetite, thirst, tongue and pulse condition, there is no significant difference between the three methods (P>0.05). In the improvement of fever, complexion, toilet and other symptoms, there is statistically significant difference (P<0.05three), Dingchuan Decoction and supermicro Dingchuan decoction is better than western medicine control group. Are all improved after treatment in three groups of FEV1and PEFR than before treatment (P<0.05), as for treatment effect,there is no significant difference between Dingchuan Decoction group and Western medicine control group (P>0.05). After treatment, increased EOS in the peripheral blood of asthma of three groups is significantly decreased,with statistical significance (P<0.01), Dingchuan Decoction group and Western medicine control group show no statistical difference (P>0.05). The three groups after treatment can significantly decrease the IL-4level in serum of patients with asthma, there is statistically significant differences (P<0.01), Dingchuan Decoction group and Western medicine control group show no statistical difference (P>0.05).
Clinical study on childhood asthma shows, total efficiency compared, difference is not statistically significant (P>0.05), and as for the clinical control rate, treatment group is obviously higher than that of the control group, the difference is statistically significant (P<0.05), as for the main symptoms and the total score points,there is significant difference between before and after treatment, as for the control group, in addition to the cyanosis, and other symptoms, there are significant differences in total integral comparison. By comparing difference of improved symptoms of each group (group t test), cough, sputum, flaring of nares, wheezing sounds have no difference (P>0.05); Dingchuan Decoction group and supermicro Dingchuan Decoction group are better than the control group in improving the wheezing, cyanosis (P<0.05). The total integral secondary symptom scores of the Dingchuan Decoction group, supermicro Dingchuan decoction group, are significantly different before and after treatment. In addition to fever, there are significant differences in total score of other symptoms before and after treatment. The comparison between the groups in improvement of symptoms, thirst, appetite, spirit of tongue, pulse,with no difference (P>0.05); fever, complexion, feces and urine are significantly different (P<0.05). Dingchuan Decoction group, supermicro Dingchuan decoction are better than the control group. Are all improved after treatment in three groups of FEV1and PEFR than before treatment (P<0.05), which shows that all groups can improve lung function. In the improvement of pulmonary function, Dingchuan Decoction group and supermicro Dingchuan Decoction group are better than western medicine control group (P<0.05).
Conclusion:
①The formation of the rat asthmatic model, has the advantages of simple operation, high success rate,and airway inflammation is clear
②he NGF, SP content in the lungs of sensitive asthmatic model rats increase. Airway mucosa, submucosa, muscle layer and pulmonary interstitial inflammation cells show significant NGF expression and localization, it can also be observed that NGFmRNA expression level is significantly increased of the site.
③ingchuan Decoction and its supermicro substance can reduce the level of NGFmRNA expression of NGF and protein levels in lung of asthma model rats, which shows that it has the improvement effects on airway neurogenic inflammation.
④he supermicro Dingchuan Decoction of1/2equivalent dose can reach the same effect of traditional decoction, can relieve the cough and phlegm, relieve asthma, can significantly improve lung function, reduce abnormal increased asthma eosinophils in peripheral blood and downregulate IL-4, superior to the western medicine control group
⑤he supermicro Dingchuan Decoction has the same effect of control group in relieving asthma and wheeze. In the improvement of cough and expectoration symptom, Dingchuan Decoction and supermicro Dingchuan decoction are better than western medicine control group, which shows Dingchuan Decoction and supermicro Dingchuan decoction have better effect in relieving asthma and cough expectorant.
⑥he supermicro Dingchuan Decoction have more obvious effect in the treatment of children febrile asthma, wheezing, cyanosis and the fever, complexion, toilet and other symptoms, while have no obvious difference in the other symptoms. The total curative effect statistics are better than western medicine control group.
⑦he supermicro Dingchuan decoction has good clinical effect in treatment of thermal asthma, and is safe
方法：①健康Sprapue-Demey大鼠随机分为正常对照组(A组)、哮喘模型组(B组)、定喘汤汤剂组(C组)、超微定喘方低剂量组(D组)、超微定喘方等剂量组(E组)。建立卵白蛋白哮喘模型,通过气道反应性测定确保模型成功。D、E组分别予定喘汤超微配方颗粒等倍剂量、1/2剂量治疗。观察NGF(Nerve growth factor)、SP (Substance P)及其mRNA (messenger Ribonucleic acid)在模型大鼠肺组织中的表达,并用显微图像分析系统测定数个视野中的阳性系数和灰度值。②采用随机方法将成人与儿童哮喘患者各90例分别分为3组,对照组给予氨茶碱加布地奈德治疗,定喘汤组在对照组基础上加定喘汤汤剂治疗,超微定喘方组在对照组基础上加超微定喘方治疗。检测治疗前后EOS (eosinophil)、IL-4(Interleukin4)及肺功能水平。
结果：五组大鼠的基础呼吸阻力(Re)相似,予生理盐水激发后的Re也相似,均无统计学意义(P>0.05)。予10～40ug/kg浓度梯度的Ach (acetylcholine)激发后,哮喘模型组Re比较正常对照组,差异有统计学意义(P<0.05)。80～160ug／kg浓度梯度的Ach激发后,哮喘模型组Re显著增加(P<0.01)。等剂量组与低剂量组之间无差异(P>0.05)。模型组的NGF、SP含量明显升高,模型组与其余组之间差异显著(P<0.01),等剂量组与低剂量组、正常组之间无差异(P>0.05)。定喘汤汤剂组、等剂量组、低剂量组大鼠肺组织NGF、NGFmRNA平均阳性系数低于模型组,差异有统计学意义(P<0.01)。
成人哮喘的临床研究显示,定喘汤组的总有效率与西医对照组相比无统计学差异,说明二者的临床疗效相近(P>0.05)。在平喘及缓解哮鸣音方面,各组比较无显著性差异(均P>0.05)。在改善咳嗽及咯痰症状方面,三者有统计学上的差异(P<0.05),定喘汤及超微定喘方优于西医对照组。在精神、口渴、食欲、舌苔脉象方面,三者比较无显著性差异(均P>0.05)。在改善发热、面色、大小便等症状方面,三者有统计学上的差异(P<0.05),定喘汤及超微定喘方优于西医对照组。疗程后三组第1秒用力呼气量及最大呼气流速较治疗前都有所提高(P<0.05),定喘汤及超微定喘方组与西医对照组治疗效果相比无统计学差异(P>0.05)。疗程后三组均能显著降低哮喘时外周血中异常升高的EOS数,统计学有显著性差异(P<0.01),定喘汤及超微定喘方组与西医对照组相比无统计学差异(P>0.05)。疗程后三组均能显著降低哮喘患者血清IL-4水平,统计学有显著性差异(P<0.01),定喘汤及超微定喘方组与西医对照组相比有统计学差异(P<0.05)。
儿童哮喘的临床研究显示,各组总有效率比较,差异无明显统计学意义(P>0.05),而临床控制率比较,治疗组明显高于对照组,差异有统计学意义(P<0.05),各组治疗前后主要症状积分、总积分比较有显著差异,对照组除对紫绀外,其他症状的前后积分、总积分比较也有显著差异。各组对症状改善经差值比较(成组t检验),咳嗽、咯痰痰鸣、鼻煽、哮呜音比较无差异(P>0.05)；定喘汤饮片组及超微定喘方组在改善喘息、紫绀症状方面优于对照组(P<0.05)。定喘汤组、超微定喘方组治疗前后次要症状积分、总积分比较均有显著差异,对照组除发热面色外,其他症状的前后积分、总积分比较也有显著差异。各组对症状改善经差值比较,精神、口渴、食欲、舌苔脉象比较无差异(P>0.05)；发热、面色、大小便比较有差异(P<0.05)。定喘汤组、超微定喘方组治优于对照组。疗程后各组第1秒用力呼气量及最大呼气流速较治疗前都有明显增加(P<0.05),说明都能改善肺功能。在改善肺功能方面,定喘汤饮片组及超微定喘方组优于西医对照组(P<0.05)。
结论：①大鼠致敏哮喘模型形成后气道炎症反应明显,具有操作简单易行,造模成功率较高的优点。②致敏大鼠哮喘模型肺内NGF、SP含量增多。气道粘膜、粘膜下层、平滑肌层及肺间质炎症细胞胞浆内均有明显的NGF的定位表达,同时也可平行地观察到上述部位显著的NGFmRNA水平表达增高。③定喘汤及其超微制剂可以减轻哮喘模型大鼠肺内NGFmRNA水平的表达及NGF蛋白水平,表明其对气道神经源性炎症有改善作用。④超微定喘方以1/2等效剂量时即可达与传统汤剂相同的作用效果,其有良好的止咳化痰、平喘作用,能显著改善肺功能,降低哮喘时外周血中异常升高的嗜酸性粒细胞,下调IL-4,作用优予西医对照组。⑤超微定喘方在平喘及缓解哮鸣音方面与对照组作用相当。在改善咳嗽及咯痰症状方面,定喘汤及超微定喘方优于西医对照组,说明定喘汤和超微定喘方均有较好的平喘、止咳化痰作用。⑥超微定喘方在治疗儿童热性哮喘中,对其喘息、紫绀以及发热、面色、大小便等症状的改善较定喘汤更为明显,而在其他症状改善方面无明显差异。总疗效统计中,明显优于西医对照组。⑦超微定喘方治疗热哮证具有较好的临床疗效,并具有良好的安全性。
Objective:
To compare effect of different doses of supermicro DingChuan Decoction on pulmonary immune neurogenic airway inflammation of thermal asthma model rats, to investigate the curative mechanism, to explore effective dose. To observe clinical effect of supermicro DingChuan Decoction on adult and childhood asthma(thermal asthma),and to detect lung function changes of patients before and after treatment,to provide evidence for its clinical application.
Methods:
①health Sprapue-Demey rats are randomly divided into normal control group (group A), asthma model group (group B), DingChuan Decoction group (group C), low-dose supermicro DingChuan Decoction group (group D), supermicro DingChuan Decoction normal dose group (group E). To make ovalbumin asthma model with airway responsiveness determination to ensure successful.Group D and E are respectively to given supermicro DingChuan soup1/2dose and normal dose. To Observe NGF and SP and its mRNA expression in lung tissue of the rat models,and to determinate several positive coefficient and grey value of vision with microscopic image analysis system.
②andomly90cases of adult and90cases childhood asthma patients are separately divided into3groups, control group are given aminophylline and budesonide therapy, besides the drugs DingChuan Decoction group are given DingChuan Decoction, supermicro DingChuan Decoction group are given supermicro DingChuan Decoction.To detecte EOS, IL-4and lung function level.before and after treatment.
Results:
The basic respiratory resistance (Re) of the five groups rats are similar both before and after with physiological saline stimulated,there is no statistical significance (P>0.05). After given10-40ug/kg of Ach excitation, the difference of asthma model group and normal control group is statistically significant (P<0.05). After given80-160ug/kg of Ach excitation, Re of asthma model group increased significantly (P<0.01). There is no difference between normal dose group and low dose group (P>0.05). NGF> SP of model group increased, the difference between model group and other groups is significant (P<0.01), there is no difference between the dose group, low dose groupand normal control group (P>0.05). average positive coefficient of NGF、NGFmRNA of lung tissue of Dingchuan Decoction group, normal dose group, low dose group rats is lower than that in the model group, the difference is statistically significant (P<0.01).
Clinical study of adult asthma shows, the difference of total efficiency between Dingchuan Decoction group and the western medicine control group have no statistical difference, which shows the two have similar clinical curative effect(P>0.05). In relieving asthma and wheeze, there is no significant difference between groups (P>0.05). In the improvement of cough and expectoration symptom, there is significant difference (P<0.05), Dingchuan Decoction and supermicro Dingchuan decoction is better than western medicine control group. In spirit, appetite, thirst, tongue and pulse condition, there is no significant difference between the three methods (P>0.05). In the improvement of fever, complexion, toilet and other symptoms, there is statistically significant difference (P<0.05three), Dingchuan Decoction and supermicro Dingchuan decoction is better than western medicine control group. Are all improved after treatment in three groups of FEV1and PEFR than before treatment (P<0.05), as for treatment effect,there is no significant difference between Dingchuan Decoction group and Western medicine control group (P>0.05). After treatment, increased EOS in the peripheral blood of asthma of three groups is significantly decreased,with statistical significance (P<0.01), Dingchuan Decoction group and Western medicine control group show no statistical difference (P>0.05). The three groups after treatment can significantly decrease the IL-4level in serum of patients with asthma, there is statistically significant differences (P<0.01), Dingchuan Decoction group and Western medicine control group show no statistical difference (P>0.05).
Clinical study on childhood asthma shows, total efficiency compared, difference is not statistically significant (P>0.05), and as for the clinical control rate, treatment group is obviously higher than that of the control group, the difference is statistically significant (P<0.05), as for the main symptoms and the total score points,there is significant difference between before and after treatment, as for the control group, in addition to the cyanosis, and other symptoms, there are significant differences in total integral comparison. By comparing difference of improved symptoms of each group (group t test), cough, sputum, flaring of nares, wheezing sounds have no difference (P>0.05); Dingchuan Decoction group and supermicro Dingchuan Decoction group are better than the control group in improving the wheezing, cyanosis (P<0.05). The total integral secondary symptom scores of the Dingchuan Decoction group, supermicro Dingchuan decoction group, are significantly different before and after treatment. In addition to fever, there are significant differences in total score of other symptoms before and after treatment. The comparison between the groups in improvement of symptoms, thirst, appetite, spirit of tongue, pulse,with no difference (P>0.05); fever, complexion, feces and urine are significantly different (P<0.05). Dingchuan Decoction group, supermicro Dingchuan decoction are better than the control group. Are all improved after treatment in three groups of FEV1and PEFR than before treatment (P<0.05), which shows that all groups can improve lung function. In the improvement of pulmonary function, Dingchuan Decoction group and supermicro Dingchuan Decoction group are better than western medicine control group (P<0.05).
Conclusion:
①The formation of the rat asthmatic model, has the advantages of simple operation, high success rate,and airway inflammation is clear
②he NGF, SP content in the lungs of sensitive asthmatic model rats increase. Airway mucosa, submucosa, muscle layer and pulmonary interstitial inflammation cells show significant NGF expression and localization, it can also be observed that NGFmRNA expression level is significantly increased of the site.
③ingchuan Decoction and its supermicro substance can reduce the level of NGFmRNA expression of NGF and protein levels in lung of asthma model rats, which shows that it has the improvement effects on airway neurogenic inflammation.
④he supermicro Dingchuan Decoction of1/2equivalent dose can reach the same effect of traditional decoction, can relieve the cough and phlegm, relieve asthma, can significantly improve lung function, reduce abnormal increased asthma eosinophils in peripheral blood and downregulate IL-4, superior to the western medicine control group
⑤he supermicro Dingchuan Decoction has the same effect of control group in relieving asthma and wheeze. In the improvement of cough and expectoration symptom, Dingchuan Decoction and supermicro Dingchuan decoction are better than western medicine control group, which shows Dingchuan Decoction and supermicro Dingchuan decoction have better effect in relieving asthma and cough expectorant.
⑥he supermicro Dingchuan Decoction have more obvious effect in the treatment of children febrile asthma, wheezing, cyanosis and the fever, complexion, toilet and other symptoms, while have no obvious difference in the other symptoms. The total curative effect statistics are better than western medicine control group.
⑦he supermicro Dingchuan decoction has good clinical effect in treatment of thermal asthma, and is safe
引文
[1]Nockher WA, Renz H. Neurotrophins and asthma:novel insight into neuroimmune interaction. J Allergy Clin Immunol,2008,117(1):67-71
[2]Braun A,Appel E,Banlch R;et al.Role of nerve gfowth factor in a mouse model of allergic airway inflammation and asthma.Eur J Immunol,1998,28(10):3240-3251
[3]Otten U,Gadient R A.Ncurotrophins and cytokines-intermediaries betreen the immunc and nervous systems.Int J Devl Neuro science,1995,13(3):147.
[4]BoniniS,Lambiase A,Bonini s,ct al.Never.growth factorian important molecule in allegic inflammation and tissue rcmodeling.Int Arch Allergy Immunol,1999,118(2):159.
[5]Harald R.Neurotrophins in bronchial asthma.Respir Res,2001,2(5):265-268.
[6]Chu DL,Song JF,Rao ZR,Qiu JY.Changes of CGRP immunoreactive nerve fibers in the lungs of asthmatic mice [J].Di si Junyi Daxue X uebao (J Fourth M il M ed niv),2001;22(13):68-1171.
[7]周新.哮喘治疗新药临床应用及开发进展[J].世界临床药物,2011,32(2)：12-14.
[8]吴夕芳.孟鲁司特钠对哮喘患儿血清IL-4、IFN-γ、IgE水平的影响及意义.山东医药,2011,51(11)：9.
[9]方萍,孙秀珍,李雅莉等.新型Th2细胞因子抑制剂甲磺司特治疗支气管哮喘的临床研究[J].西安交通大学学报(医学版),2009,30(5)：575-578.
[10]Sorkness CA, Lemanske RF, Manger DT. Long-term comparison of three controller regimens for mild-moderate persistent childhood asthma:the pediatric asthma controller Trial(PACT). J Allergy Clin Immunol,2007,119(1):64-72.
[11]Devillier P, Acker GM, Advenier C, Marsac J, Regoli D, Frossard N. Activation of an epithelial neurokinin NK-1 reccptor induces relaxation of rat trachea through release of prostaglandin E2. J Phamacol ExpTher 1992;263:767-772.
[12]Joos GF,Gouture R, Pouwels RA. Role of tachykinins in asthma.A 11 ergy 2000;55:321-337.
[13]陈奇.中药药理研究方法学[M].第1版.北京,人民卫生出版社,1994.
[14]Richerson,HB Acute.ExPerimental HyPersensitivity Pneumonia in the Guinea piss[J].Clin Med,1972,79(5):745-757.
[15]戴继红.谭毅等,哮喘动物模型的研究现状,中国实验动物学杂志2001(11)3,167-170.
[16]颜晓燕,等.哮喘动物模型研究现状,成都医学院学报.2007(2)2,156-157.
[17]哈小博.漫谈定喘汤[J].开卷有益,2003,(3)：21.
[18]骆和生.中药与免疫[M].广州：广东科技出版社.1990：25.
[19]张洪泉,等.银杏外种皮水溶性成分的抗过敏作用[J].中国中药杂志,1990,15(8)：48.
[20]李忠.免疫中药学[M].郑州：河南医科大学出版社,1996.
[21]蔡仙德,等.黄芩甙对小鼠免疫功能的影响[J].南京铁道医学院学报.1994,13(2)：65.
[22]王慧新,等.黄芩甙对小鼠红细胞免疫粘附功能的作用[J].中国实验临床免疫学杂志,1992,3：41.
[23]骆和生,等主编.中药方剂的药理与临床研究进展[M].广州：华南理工大学学报出版社.1990.
[24]骆和生,罗鼎辉.免疫中药学[M].北京协和医科大学联合出版社[M].1990
[25]徐长化,等.定喘汤及其拆方的药理作用[J].中国医院药学杂志[J].2002,22(4)：4
[26]李顺花.定喘汤对支气管哮喘大鼠总IgE及IL4的影响[J].中医药学刊,2004,22(11)：121.
[27]李家发.定喘汤及其拆方化痰平喘抗炎作用实验研究[J].中国实验方剂学杂志,2002,8(5)：16.
[28]肖丽玲,伍参荣,唐小梅.定喘汤对大鼠NO,ET-I,IL一5的影响.中国实验方剂学杂志,2005,6(3)：58-59
[29]徐华雄,杨永华,蔡光先.含人参皂苷类超微饮片与其传统饮片的化学对比研究[J].中国实验方剂学杂志,2002,8(5)：13-14.
[30]王实强,杨瑛,舒建斌,蔡光先.RP-HPLC法测定肉桂超微饮片中桂皮醛的含量[J].中国实验方剂学杂志,2000,8(5)：15,17.
[31]袁红宇.苍术、黄柏及二妙九超细微粉的生物药剂学的研究Ⅱ超细粉二妙丸的体外溶出度的研究[J].中草药,2002,33(9)：790-792.
[32].苏瑞强,何煌,王瑞成,等.超微粉碎技术提高六味地黄丸(水蜜丸)溶出度的研究[J].中国中药杂志,2002,27(7)511-513.
[33].杨永刚,赵浩如.肉桂油p-环糊精包合物与肉桂超细微粉药剂学性质的对比研究[J].中国药科大学学报,2002,33(57)：388-392.
[34].郭学东.比较红参普通粉和微粉化处理的溶出速率[J].首都医药,2000,7(9)：47-49.
[35]郭学东.山茱萸普通粉碎和微粉化处理在溶出速率上的比较[J].首都医药,2000,7(8)45-48.
[36].杜晓敏,刘璐,何煌.原生药材超细粉制剂的药效学研究[J].中草药,1999,30(9)680.
[37].蔡光先,郑兵,郑艳辉,等.小青龙汤超微饮片与传统饮片药理作用对比研究团.中国医药学报,2004,(19)：729-730.
[38].郑兵,首弟武,陈立峰,等,便可通超微饮片与传统饮片药理作用对比研究[J].中药药理与临床,2004；20(2)：4142.
[39].唐利文,刘正刚,蔡光先,等.止漱散超微速溶颗粒治疗单纯型慢性支气管炎急性发作期临床观察[J].湖南中医学院学报,2005,25(3)31-33.
[40].刘智,李诚秀,李玲.天麻粉不同粒径的镇静镇痛作用研究[J].中国现代应用药学杂志,2002,19(5)：383.
[41].宁丽丽,桂钢军,范丙义,等.六味地黄方超细粉药理学研究[J].中国中药杂志,2002,27(6)：436
[42]蔡光先,杨永华,李跃辉.超微粉体技术与中药饮片改革[J].世界科学技术-中医药现代化,2004,6(2)：67-70
[43]汪文涛.中药超微饮片质量控制与安全性探讨[J].世界科学技术-中医药现代化,2004,6(3)：37-40,54
[44].蔡光先,杨永华,李雅.中药超细粉体研究概况[J].科技导报,2007,25(10),50-52.
[45]方邦江,陈浩,郭全,等.中药超微粉的优势及应用前景[J].中国中医药现代远程教育,2010,8(18),208-209.
[46]Lindsay RM, Harmar AJ. Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature,1989,337:362-364.
[47]Woolf CJ. Phenotypic modification of primary sensory neurons:the role of nerve growth factor in the production of persistent pain. Philosophical Transections ofthe Royal society ofLondon series B, Biological Science,1996,351(1338):441—448.
[48]Bonini S, Lambiase A, Bonini S, et al. Circulating nerve growth factor levels areincreased in humans with allergic diseases and asthma. Proc Natl Acad Sci USA,1996,93(20):10955-10960.
[49]Virchow JC, Julius P, Lommatzsch M, et al. Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation. Am J RespirCfit Care Med,1998,158(6):2002-2005.
[50]Braun A, Lommatzsch M, Lewin GR et al. Neurotrophins:a link between airway inflammation and airway smooth muscle contractility in asthma?Int Arch Allergy Immunol,1999,118(2-4):163-165.
[51]NogaO, Hard G SchaperC, etal. Theinfluence ofinhalative coaicosteroids on circulating Nerve Growth Factor,Brain—Derived Neurotrophic Factor and Neurotrophin-3 in allergic asthmatics. Clin Exp llergy,2001.31(12):1906-1912.
[52]Braun A'Appel E, Baruch R et al. Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma. Eur J Imuntmol,1998,28:3240-3251.
[53]Olgart Hoglund C, deBlay F, Oster JR et al. Nerve growth factor levels and localisationinhuman asthmaticbronchi. EurRespir J,2002,20(5):1110-1116.
[54]De Vries A,Dessing MC, Engels F'et al. Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperresponsiveness in guinea pigs. Am J Respir Crit Care Med,1999,159(5 Pt 1):1541-1544.
[55]Friberg SG Olgart HC, Gustafsson LE. Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea-pig model. Acta Phy'siol Scand,2001,173(2):239-245.
[56]Maming CR, Theodorsson-Norheim E, Lundberg JM.1987. Occurrence and effccts of muniple tachykinins:Substance P,neurobllin A,and neumpeptide K in human lower airways, Ljfe Sci 40(16):1633-643.
[57]Watson N, Madagan J, Barens PJ. Endogenous tachykinins facilitate transmission through parasympathetic ganglia in guillca-pig trachea. Br J Phannacol 1993:109:751-759.
[58]Van PM, Hofland Lj, Ten AM. Ncuropeptides and their receptors in the immune system[J]. Ann Med, 1999,31(suppl):15-22.
[59]Covas MJ, Pinto LA, victorino RM. Effeds of substance P on human T cell function and the modulation mle of peptidase in hibitof. Int J Clin Lab Res,1997.27:129-134.
[60]李成仁,蔡文琴,邓晓林.P物质对大鼠脾细胞免疫功能的影响[J].第三军医大学学报,1999,21(12)：896-898.
[61]Ka wamura N, Tamura H, Obana s, et al.Differential effects of neuropeptides on cytokine production by mouse helper T cell sub-sets. Neurojmmunomodulation,1998,5(1-2):9-15.
[62]Bockmann S, Seep J,Jonas L Delay of neurophil apoptosis by the neuropeptides substance Prinvement ofcaspase cascade. Peptjdes,2001,22(4):211-214.
[63]Gende K, Kubiak H.A morphologcal and immunohistochemjcal investigation of guionea pig skin after the intrduction of substance P and VIP[J].cellular Molecular Biology htters,2003,8(1):63-67.
[64]Kradin R, Maclean J, Ducketc s, et al. Pulmonry response to inaled antigen:neuroimmune interactions promote the recruitment Of dendritic cells to the lung and the cellular immune rcsponse to inhale antjgen[J]. Am Jpathol,1997,150(5):1735-1743.
[65]Qian BF,zhou GQ, Hammarstmm ML, et al. Both substance P and its receptor are exprcssed in mouse intestinal T lymphocytes[J]. Neuroendocrinology,2001,73:358-368.
[66]De GR, Tazzari PL,Barbara Get al. Detecion of substantmce P immunoreactivity in human peripheral leukocytes[J]Neuroimmunol,1998,82(2):175-181.
[67]Lambrecht BN, Germonpre PR, Everaert EQet al. Endogenously pfoduced substance P contributes to lynlphocyte pfolifcratiOn induccd by dendritic cells and dircct TcR ligation[J], EurJ I mmunol,1999, 29(12):3815.3825.
[68]Santoni G, AmaⅡtini c, Luccarini R, et al. Exprcssion of substance P and its neurokjnin-lreceptor on thymocytes:functional of thymocyte apoptosis and proliferation[J]Neuroimmuno modulation,2003, 10(4):232-246.
[69]Boden G. Role of fatty acjdS in the patllogenesis of insulin resistallc and NIDDM[J], Diabetes,1997, 46(1):3-10.
[70]Qian BF, Elsalhy M, MelgarS, et al. Neuroendocrjlle changes in colon of mice winl a disrupted IL-2 gene[J]. Clin Exp Immunol,2000,120:424-433.361,
[71]Braun A,Apple E, Baruch R,et al. Role Of nerve growth factor in a mouse model of allegic airway inflanmation and asthma.Eur J Immunol,1998,28(10).3240-3251.
[71]李东培,才丽平,方秀斌.哮喘豚鼠下呼吸道及内脏传入部位NGF表达的研究.解剖学报,2002,33(41：350.354.
[72]Harrjson NK, Dawes KE, Kwon OJ, Barnes PJ, Laurent GJ, Chung KF,1995. Effects of neuropepiides on human lung fibroblast proliferation and chemotaxos,Am J Physiol,1995; 12:L278-283.
[73]Freund V Frossard N. Expression of nerve growth factor in the airways and its possible role in asthma. Prog Brain Res 2004; 146:335-346.
[74]De GR,Tazzari PL,Barbara G et al. Detection Of substance P immunoreaclivity in human peripheral leukocytes Neuroimmunol,1998,82(2):175-181.
[75]陈力.微米中药及其制备技术[J].中草药,2002,33(10)：865-868
[76]蔡光先,刘柏炎.28味常用中药饮片汤荆与散剂中的用量研究[J].中国实验方剂学杂志,2004,10(2)：63-64.
[77]中华人民共和国卫生部.中药新药临床研究指导原则.1995.
[78]国家中医药管理局.哮病的诊断依据、征候分类、疗效评定、中医病证诊断疗效标准.南京：南京大学出版社,1994,5.
[79]中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南：支气管哮喘的定义、诊断、治疗和管理方案[S].中华结核和呼吸杂志,2008,31(3)：177--185
[80]沈晓明,王卫平.儿科学[M]人民卫生出版社,268-269.
[81]中华医学会儿科学分会呼吸学组.儿童支气管哮喘诊断与防治指南(2008年修订),《中华儿科杂志》编辑委员会.
[82]汪受传主编.中医儿科学,北京：中国中医药出版社出版,2007年.
[83]陈友华,黄俊辉,吴霞,等.顺尔宁治疗儿童支气管哮喘46例临床分析[J].河北医学,2011,17(7)：881-883.
[84]盛宾杰.定喘汤治疗小儿哮喘临床观察[J].光明中医,2008,23(2)：199-200.
[1]刘立虎,刘东辉,徐宜全.支气管哮喘的治疗现状与进展[J].临床荟萃2010,25(7)：632-635.
[2]王静海.支气管哮喘药物治疗进展[J].中国现代医生,2009,47(16)：45-48.
[3]李春娟.浅谈支气管哮喘的治疗[J].中国中医药现代远程教育,2010,8(5)：102.
[4]上官文姬,沈惠风.支气管哮喘免疫学发病机制的研究进展[J].上海交通大学学报(医学版),2009,29(5)：602-605.
[5]冯婧.中西药联合治疗支气管哮喘30例[J].中国中医药现代远程教育,2009,9(151)：39-40.
[6]陈跃飞,胡剑卓,罗仕德,等.定喘汤治疗支气管哮喘32例[J].中国中医药现代远程教育,2009,7(12)：207-208.
[7]秦双件,何军锋.射干麻黄汤化裁方配合西药治疗支气管哮喘(寒哮)急性发作期30例[J].中国中医药现代远程教育,2009,7(1)：29-30.
[8]成菲.越婢加半夏汤治疗支气管哮喘急性发作期热哮证35例[J]中国中医药现代远程教育,2010,8(13)：25-26.
[9]张彦来.三子养亲汤治疗支气管哮喘40例[J].中国中医药现代远程教育,2009 7(9)：26.
[10]祝咏梅.麻杏定喘汤治疗儿童咳嗽变异性哮喘30例[J].中国中医药现代远程教育,2010,8(3)：36.
[11]沈宁.中医治疗支气管哮喘缓解期的进展[J].中国中医药现代远程教育,2009,7(6)：87-89.
[12]任绪才.中医治疗哮喘的浅析[J].中国中医药现代远程教育,2010,8(11)：111
[13]张诚.五味咳喘停辨证治疗慢性哮喘50例[J].中国中医药现代远程教育,2010,8(16)：34-35.
[14]赖祥林.中西医结合治疗哮喘急性发作期255例临床观察[J].实用中西医结合杂 志,1995,8(10)：588-589.
[15]刘陈.中药穴位敷贴治疗支气管哮喘15例[J].中国中医药现代远程教育,2010,8(2)：35.
[16]叶宗仁,高尚德,叶丰次,等.麻杏石甘汤拆方对过敏性气喘的研究[J].新中医,1998,(30)：40-41.
[17]宋修军,宫卫星.祛瘀定喘合剂治疗支气管哮喘慢性持续期痰瘀阻肺证32例[J].中国中医药现代远程教育,2010,8(13)：35-36.
[18]丁汀,陈品菊.“宁喘微型灌肠液”的平喘实验研究[J].浙江中医学院学报200024(2)：52.53.
[19]蔡宛如,钱华.芍药甘草汤平喘和抗过敏作用的实验研究[J].中国中西医结合急救杂志,2000,7(6)：341-342.
[20]李仪奎,吴健宇,吴晓芬,等.青龙汤药物血清对致敏大鼠腹腔肥大细胞脱颗粒以及组织胺释放的影响[J].中国中西医结合杂志,2000,20(1)40-42.
[21]张有志,聂惠民,张宁,等.桂枝加厚朴杏予汤加味对过敏性哮喘豚鼠肿瘤坏死因子、内皮素的影响[J].北京中医药大学学报,2000,23(2)：23-24.
[2]Braun A,Appel E,Banlch R;et al.Role of nerve gfowth factor in a mouse model of allergic airway inflammation and asthma.Eur J Immunol,1998,28(10):3240-3251
[3]Otten U,Gadient R A.Ncurotrophins and cytokines-intermediaries betreen the immunc and nervous systems.Int J Devl Neuro science,1995,13(3):147.
[4]BoniniS,Lambiase A,Bonini s,ct al.Never.growth factorian important molecule in allegic inflammation and tissue rcmodeling.Int Arch Allergy Immunol,1999,118(2):159.
[5]Harald R.Neurotrophins in bronchial asthma.Respir Res,2001,2(5):265-268.
[6]Chu DL,Song JF,Rao ZR,Qiu JY.Changes of CGRP immunoreactive nerve fibers in the lungs of asthmatic mice [J].Di si Junyi Daxue X uebao (J Fourth M il M ed niv),2001;22(13):68-1171.
[7]周新.哮喘治疗新药临床应用及开发进展[J].世界临床药物,2011,32(2)：12-14.
[8]吴夕芳.孟鲁司特钠对哮喘患儿血清IL-4、IFN-γ、IgE水平的影响及意义.山东医药,2011,51(11)：9.
[9]方萍,孙秀珍,李雅莉等.新型Th2细胞因子抑制剂甲磺司特治疗支气管哮喘的临床研究[J].西安交通大学学报(医学版),2009,30(5)：575-578.
[10]Sorkness CA, Lemanske RF, Manger DT. Long-term comparison of three controller regimens for mild-moderate persistent childhood asthma:the pediatric asthma controller Trial(PACT). J Allergy Clin Immunol,2007,119(1):64-72.
[11]Devillier P, Acker GM, Advenier C, Marsac J, Regoli D, Frossard N. Activation of an epithelial neurokinin NK-1 reccptor induces relaxation of rat trachea through release of prostaglandin E2. J Phamacol ExpTher 1992;263:767-772.
[12]Joos GF,Gouture R, Pouwels RA. Role of tachykinins in asthma.A 11 ergy 2000;55:321-337.
[13]陈奇.中药药理研究方法学[M].第1版.北京,人民卫生出版社,1994.
[14]Richerson,HB Acute.ExPerimental HyPersensitivity Pneumonia in the Guinea piss[J].Clin Med,1972,79(5):745-757.
[15]戴继红.谭毅等,哮喘动物模型的研究现状,中国实验动物学杂志2001(11)3,167-170.
[16]颜晓燕,等.哮喘动物模型研究现状,成都医学院学报.2007(2)2,156-157.
[17]哈小博.漫谈定喘汤[J].开卷有益,2003,(3)：21.
[18]骆和生.中药与免疫[M].广州：广东科技出版社.1990：25.
[19]张洪泉,等.银杏外种皮水溶性成分的抗过敏作用[J].中国中药杂志,1990,15(8)：48.
[20]李忠.免疫中药学[M].郑州：河南医科大学出版社,1996.
[21]蔡仙德,等.黄芩甙对小鼠免疫功能的影响[J].南京铁道医学院学报.1994,13(2)：65.
[22]王慧新,等.黄芩甙对小鼠红细胞免疫粘附功能的作用[J].中国实验临床免疫学杂志,1992,3：41.
[23]骆和生,等主编.中药方剂的药理与临床研究进展[M].广州：华南理工大学学报出版社.1990.
[24]骆和生,罗鼎辉.免疫中药学[M].北京协和医科大学联合出版社[M].1990
[25]徐长化,等.定喘汤及其拆方的药理作用[J].中国医院药学杂志[J].2002,22(4)：4
[26]李顺花.定喘汤对支气管哮喘大鼠总IgE及IL4的影响[J].中医药学刊,2004,22(11)：121.
[27]李家发.定喘汤及其拆方化痰平喘抗炎作用实验研究[J].中国实验方剂学杂志,2002,8(5)：16.
[28]肖丽玲,伍参荣,唐小梅.定喘汤对大鼠NO,ET-I,IL一5的影响.中国实验方剂学杂志,2005,6(3)：58-59
[29]徐华雄,杨永华,蔡光先.含人参皂苷类超微饮片与其传统饮片的化学对比研究[J].中国实验方剂学杂志,2002,8(5)：13-14.
[30]王实强,杨瑛,舒建斌,蔡光先.RP-HPLC法测定肉桂超微饮片中桂皮醛的含量[J].中国实验方剂学杂志,2000,8(5)：15,17.
[31]袁红宇.苍术、黄柏及二妙九超细微粉的生物药剂学的研究Ⅱ超细粉二妙丸的体外溶出度的研究[J].中草药,2002,33(9)：790-792.
[32].苏瑞强,何煌,王瑞成,等.超微粉碎技术提高六味地黄丸(水蜜丸)溶出度的研究[J].中国中药杂志,2002,27(7)511-513.
[33].杨永刚,赵浩如.肉桂油p-环糊精包合物与肉桂超细微粉药剂学性质的对比研究[J].中国药科大学学报,2002,33(57)：388-392.
[34].郭学东.比较红参普通粉和微粉化处理的溶出速率[J].首都医药,2000,7(9)：47-49.
[35]郭学东.山茱萸普通粉碎和微粉化处理在溶出速率上的比较[J].首都医药,2000,7(8)45-48.
[36].杜晓敏,刘璐,何煌.原生药材超细粉制剂的药效学研究[J].中草药,1999,30(9)680.
[37].蔡光先,郑兵,郑艳辉,等.小青龙汤超微饮片与传统饮片药理作用对比研究团.中国医药学报,2004,(19)：729-730.
[38].郑兵,首弟武,陈立峰,等,便可通超微饮片与传统饮片药理作用对比研究[J].中药药理与临床,2004；20(2)：4142.
[39].唐利文,刘正刚,蔡光先,等.止漱散超微速溶颗粒治疗单纯型慢性支气管炎急性发作期临床观察[J].湖南中医学院学报,2005,25(3)31-33.
[40].刘智,李诚秀,李玲.天麻粉不同粒径的镇静镇痛作用研究[J].中国现代应用药学杂志,2002,19(5)：383.
[41].宁丽丽,桂钢军,范丙义,等.六味地黄方超细粉药理学研究[J].中国中药杂志,2002,27(6)：436
[42]蔡光先,杨永华,李跃辉.超微粉体技术与中药饮片改革[J].世界科学技术-中医药现代化,2004,6(2)：67-70
[43]汪文涛.中药超微饮片质量控制与安全性探讨[J].世界科学技术-中医药现代化,2004,6(3)：37-40,54
[44].蔡光先,杨永华,李雅.中药超细粉体研究概况[J].科技导报,2007,25(10),50-52.
[45]方邦江,陈浩,郭全,等.中药超微粉的优势及应用前景[J].中国中医药现代远程教育,2010,8(18),208-209.
[46]Lindsay RM, Harmar AJ. Nerve growth factor regulates expression of neuropeptide genes in adult sensory neurons. Nature,1989,337:362-364.
[47]Woolf CJ. Phenotypic modification of primary sensory neurons:the role of nerve growth factor in the production of persistent pain. Philosophical Transections ofthe Royal society ofLondon series B, Biological Science,1996,351(1338):441—448.
[48]Bonini S, Lambiase A, Bonini S, et al. Circulating nerve growth factor levels areincreased in humans with allergic diseases and asthma. Proc Natl Acad Sci USA,1996,93(20):10955-10960.
[49]Virchow JC, Julius P, Lommatzsch M, et al. Neurotrophins are increased in bronchoalveolar lavage fluid after segmental allergen provocation. Am J RespirCfit Care Med,1998,158(6):2002-2005.
[50]Braun A, Lommatzsch M, Lewin GR et al. Neurotrophins:a link between airway inflammation and airway smooth muscle contractility in asthma?Int Arch Allergy Immunol,1999,118(2-4):163-165.
[51]NogaO, Hard G SchaperC, etal. Theinfluence ofinhalative coaicosteroids on circulating Nerve Growth Factor,Brain—Derived Neurotrophic Factor and Neurotrophin-3 in allergic asthmatics. Clin Exp llergy,2001.31(12):1906-1912.
[52]Braun A'Appel E, Baruch R et al. Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma. Eur J Imuntmol,1998,28:3240-3251.
[53]Olgart Hoglund C, deBlay F, Oster JR et al. Nerve growth factor levels and localisationinhuman asthmaticbronchi. EurRespir J,2002,20(5):1110-1116.
[54]De Vries A,Dessing MC, Engels F'et al. Nerve growth factor induces a neurokinin-1 receptor-mediated airway hyperresponsiveness in guinea pigs. Am J Respir Crit Care Med,1999,159(5 Pt 1):1541-1544.
[55]Friberg SG Olgart HC, Gustafsson LE. Nerve growth factor increases airway responses and decreases levels of exhaled nitric oxide during histamine challenge in an in vivo guinea-pig model. Acta Phy'siol Scand,2001,173(2):239-245.
[56]Maming CR, Theodorsson-Norheim E, Lundberg JM.1987. Occurrence and effccts of muniple tachykinins:Substance P,neurobllin A,and neumpeptide K in human lower airways, Ljfe Sci 40(16):1633-643.
[57]Watson N, Madagan J, Barens PJ. Endogenous tachykinins facilitate transmission through parasympathetic ganglia in guillca-pig trachea. Br J Phannacol 1993:109:751-759.
[58]Van PM, Hofland Lj, Ten AM. Ncuropeptides and their receptors in the immune system[J]. Ann Med, 1999,31(suppl):15-22.
[59]Covas MJ, Pinto LA, victorino RM. Effeds of substance P on human T cell function and the modulation mle of peptidase in hibitof. Int J Clin Lab Res,1997.27:129-134.
[60]李成仁,蔡文琴,邓晓林.P物质对大鼠脾细胞免疫功能的影响[J].第三军医大学学报,1999,21(12)：896-898.
[61]Ka wamura N, Tamura H, Obana s, et al.Differential effects of neuropeptides on cytokine production by mouse helper T cell sub-sets. Neurojmmunomodulation,1998,5(1-2):9-15.
[62]Bockmann S, Seep J,Jonas L Delay of neurophil apoptosis by the neuropeptides substance Prinvement ofcaspase cascade. Peptjdes,2001,22(4):211-214.
[63]Gende K, Kubiak H.A morphologcal and immunohistochemjcal investigation of guionea pig skin after the intrduction of substance P and VIP[J].cellular Molecular Biology htters,2003,8(1):63-67.
[64]Kradin R, Maclean J, Ducketc s, et al. Pulmonry response to inaled antigen:neuroimmune interactions promote the recruitment Of dendritic cells to the lung and the cellular immune rcsponse to inhale antjgen[J]. Am Jpathol,1997,150(5):1735-1743.
[65]Qian BF,zhou GQ, Hammarstmm ML, et al. Both substance P and its receptor are exprcssed in mouse intestinal T lymphocytes[J]. Neuroendocrinology,2001,73:358-368.
[66]De GR, Tazzari PL,Barbara Get al. Detecion of substantmce P immunoreactivity in human peripheral leukocytes[J]Neuroimmunol,1998,82(2):175-181.
[67]Lambrecht BN, Germonpre PR, Everaert EQet al. Endogenously pfoduced substance P contributes to lynlphocyte pfolifcratiOn induccd by dendritic cells and dircct TcR ligation[J], EurJ I mmunol,1999, 29(12):3815.3825.
[68]Santoni G, AmaⅡtini c, Luccarini R, et al. Exprcssion of substance P and its neurokjnin-lreceptor on thymocytes:functional of thymocyte apoptosis and proliferation[J]Neuroimmuno modulation,2003, 10(4):232-246.
[69]Boden G. Role of fatty acjdS in the patllogenesis of insulin resistallc and NIDDM[J], Diabetes,1997, 46(1):3-10.
[70]Qian BF, Elsalhy M, MelgarS, et al. Neuroendocrjlle changes in colon of mice winl a disrupted IL-2 gene[J]. Clin Exp Immunol,2000,120:424-433.361,
[71]Braun A,Apple E, Baruch R,et al. Role Of nerve growth factor in a mouse model of allegic airway inflanmation and asthma.Eur J Immunol,1998,28(10).3240-3251.
[71]李东培,才丽平,方秀斌.哮喘豚鼠下呼吸道及内脏传入部位NGF表达的研究.解剖学报,2002,33(41：350.354.
[72]Harrjson NK, Dawes KE, Kwon OJ, Barnes PJ, Laurent GJ, Chung KF,1995. Effects of neuropepiides on human lung fibroblast proliferation and chemotaxos,Am J Physiol,1995; 12:L278-283.
[73]Freund V Frossard N. Expression of nerve growth factor in the airways and its possible role in asthma. Prog Brain Res 2004; 146:335-346.
[74]De GR,Tazzari PL,Barbara G et al. Detection Of substance P immunoreaclivity in human peripheral leukocytes Neuroimmunol,1998,82(2):175-181.
[75]陈力.微米中药及其制备技术[J].中草药,2002,33(10)：865-868
[76]蔡光先,刘柏炎.28味常用中药饮片汤荆与散剂中的用量研究[J].中国实验方剂学杂志,2004,10(2)：63-64.
[77]中华人民共和国卫生部.中药新药临床研究指导原则.1995.
[78]国家中医药管理局.哮病的诊断依据、征候分类、疗效评定、中医病证诊断疗效标准.南京：南京大学出版社,1994,5.
[79]中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南：支气管哮喘的定义、诊断、治疗和管理方案[S].中华结核和呼吸杂志,2008,31(3)：177--185
[80]沈晓明,王卫平.儿科学[M]人民卫生出版社,268-269.
[81]中华医学会儿科学分会呼吸学组.儿童支气管哮喘诊断与防治指南(2008年修订),《中华儿科杂志》编辑委员会.
[82]汪受传主编.中医儿科学,北京：中国中医药出版社出版,2007年.
[83]陈友华,黄俊辉,吴霞,等.顺尔宁治疗儿童支气管哮喘46例临床分析[J].河北医学,2011,17(7)：881-883.
[84]盛宾杰.定喘汤治疗小儿哮喘临床观察[J].光明中医,2008,23(2)：199-200.
[1]刘立虎,刘东辉,徐宜全.支气管哮喘的治疗现状与进展[J].临床荟萃2010,25(7)：632-635.
[2]王静海.支气管哮喘药物治疗进展[J].中国现代医生,2009,47(16)：45-48.
[3]李春娟.浅谈支气管哮喘的治疗[J].中国中医药现代远程教育,2010,8(5)：102.
[4]上官文姬,沈惠风.支气管哮喘免疫学发病机制的研究进展[J].上海交通大学学报(医学版),2009,29(5)：602-605.
[5]冯婧.中西药联合治疗支气管哮喘30例[J].中国中医药现代远程教育,2009,9(151)：39-40.
[6]陈跃飞,胡剑卓,罗仕德,等.定喘汤治疗支气管哮喘32例[J].中国中医药现代远程教育,2009,7(12)：207-208.
[7]秦双件,何军锋.射干麻黄汤化裁方配合西药治疗支气管哮喘(寒哮)急性发作期30例[J].中国中医药现代远程教育,2009,7(1)：29-30.
[8]成菲.越婢加半夏汤治疗支气管哮喘急性发作期热哮证35例[J]中国中医药现代远程教育,2010,8(13)：25-26.
[9]张彦来.三子养亲汤治疗支气管哮喘40例[J].中国中医药现代远程教育,2009 7(9)：26.
[10]祝咏梅.麻杏定喘汤治疗儿童咳嗽变异性哮喘30例[J].中国中医药现代远程教育,2010,8(3)：36.
[11]沈宁.中医治疗支气管哮喘缓解期的进展[J].中国中医药现代远程教育,2009,7(6)：87-89.
[12]任绪才.中医治疗哮喘的浅析[J].中国中医药现代远程教育,2010,8(11)：111
[13]张诚.五味咳喘停辨证治疗慢性哮喘50例[J].中国中医药现代远程教育,2010,8(16)：34-35.
[14]赖祥林.中西医结合治疗哮喘急性发作期255例临床观察[J].实用中西医结合杂 志,1995,8(10)：588-589.
[15]刘陈.中药穴位敷贴治疗支气管哮喘15例[J].中国中医药现代远程教育,2010,8(2)：35.
[16]叶宗仁,高尚德,叶丰次,等.麻杏石甘汤拆方对过敏性气喘的研究[J].新中医,1998,(30)：40-41.
[17]宋修军,宫卫星.祛瘀定喘合剂治疗支气管哮喘慢性持续期痰瘀阻肺证32例[J].中国中医药现代远程教育,2010,8(13)：35-36.
[18]丁汀,陈品菊.“宁喘微型灌肠液”的平喘实验研究[J].浙江中医学院学报200024(2)：52.53.
[19]蔡宛如,钱华.芍药甘草汤平喘和抗过敏作用的实验研究[J].中国中西医结合急救杂志,2000,7(6)：341-342.
[20]李仪奎,吴健宇,吴晓芬,等.青龙汤药物血清对致敏大鼠腹腔肥大细胞脱颗粒以及组织胺释放的影响[J].中国中西医结合杂志,2000,20(1)40-42.
[21]张有志,聂惠民,张宁,等.桂枝加厚朴杏予汤加味对过敏性哮喘豚鼠肿瘤坏死因子、内皮素的影响[J].北京中医药大学学报,2000,23(2)：23-24.
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