清热利湿法对支气管哮喘的临床疗效评价和实验研究

发布时间：2018-05-12 16:31

本文选题：清热利湿法 + 茵陈蒿汤加减方　；参考：《北京中医药大学》2015年博士论文

【摘要】：本课题通过临床研究以及实验研究的方法探讨了中医药对支气管哮喘的认识和中医药治疗本病的疗效及作用机理,为今后更好的治疗哮喘,并防止其进一步发展为难治性哮喘,以及中药新药开发提供可靠临床与实验依据。分为三个部分进行论述：1文献综述通过近年的国内外文献资料检索,探讨了支气管哮喘的中医病名归属、病因病机、治疗原则与辨证论治以及TGF-β1/Smads信号通路在支气管哮喘气道重塑中的作用。2清热利湿法治疗支气管哮喘的临床研究目的观察清热利湿法治疗支气管哮喘的临床疗效。方法将所有符合本研究纳入标准的哮喘患儿共34例,其中中药组17例,西药组17例。分别予以茵陈蒿汤加减方免煎颗粒以及西药孟鲁司特钠口服治疗7天,观察治疗前后患儿的临床症状、中医证候改善情况,并进行系统的疗效评价。结果(1)本临床观察分组患儿在性别,年龄,治疗前证候积分方面比较,均无明显差异,P0.05,具有可比性。(2)本研究结果表明：从临床疗效比较,中药组17例,其中临床痊愈7例,显效6例,有效4例,无效0例,总有效率100.00%：西药组17例,临床痊愈1例,显效5例,有效6例,无效5例,总有效率70.59%。经统计学处理分析,中药组痊愈率和总有效率优于西药组,说明中药对于湿热哮喘的疗效更好。(3)从中医证候积分来看,两组患者治疗前后总积分均有明显改善,比较具有显著统计学意义,提示两组均可有效控制哮喘主要证候,且中药组疗效优于西药组。中药组与西药组治疗前后次要证候积分比较具有显著性差异,P均0.001；说明两组均次要证候减轻,但控制次要证候上中药组效果更佳,表明中药辨证论治对于湿热哮喘的湿热症状有很好的改善作用,而湿热症状的改善直接关系整个病程的疗效。(4)清热利湿法治疗支气管哮喘疗效显著,且临床未见不良反应。3清热利湿法治疗支气管哮喘的实验研究目的(1)从整体动物水平探讨“茵陈蒿汤加减方”对支气管哮喘的治疗作用及其对气道重塑的改善作用；(2)以TGF-β1/Smads信号通路为切入点,从基因与蛋白水平探讨清热利湿法干预支气管哮喘气道重塑的分子机制。方法(1)药效学的研究采用卵蛋白与氢氧化铝溶液注射、雾化等综合方法制备支气管哮喘大鼠模型,各用药组分别给予茵陈蒿汤加减方及地塞米松进行干预,正常组及模型组给予等量生理盐水干预,治疗4周后处死大鼠,留取血清和肺组织,观察各组大鼠一般状态,肺脏病理改变,肺泡灌洗液中(BALF)炎性细胞变化,气道壁的面积和厚度的变化。(2) TGF-β1/Smads信号通路的研究采用卵蛋白与氢氧化铝溶液注射、雾化等综合方法制备支气管哮喘大鼠模型,各用药组分别给予茵陈蒿汤加减方及地塞米松进行干预,正常组及模型组给予等量生理盐水干预,治疗4周后处死大鼠,留取血清和肺组织,肺组织Ⅰ型胶原、Ⅲ型胶原、Smad2、 Smad3、Smad7的蛋白表达以及肺组织TGF-β1、Smad2、Smad3、Smad7 mRNA的表达。结果(1)肺组织病理形态学：模型组肺组织炎症、水肿程度较正常组明显加重；与模型组相比,各用药组则均有改善。(2)BALF中细胞沉淀涂片：模型组炎症细胞较正常组明显增多；与模型组相比,各用药组炎性细胞明显减少。(3) BALF中TGF-β1表达水平：与正常组相比,模型组血清、BALF中TGF-β1表达水平升高,差异显著(P0.05),而用药组较模型组则下降(P0.05)。(4)肺组织Ⅰ型胶原、Ⅲ型胶原、Smad2、Smad3、Smad7的蛋白表达：模型组肺组织中Ⅰ型胶原、Ⅲ型胶原、Smad2、Smad3的蛋白表达,Smad7的蛋白表达与正常组比较,差异有统计学意义(P0.05)；用药组与模型组比较,Ⅰ型胶原、Ⅲ型胶原、Smad2、Smad3的蛋白表达下调,Smad7的蛋白表达上调,差异有统计学意义(P0.05)。(5)肺组织TGF-β1、Smad2、Smad3、Smad7 mRNA的表达。模型组肺组织中TGF-β1、Smad2、Smad3 mRNA的表达上调,Smad7 mRNA的表达下调与正常组比较,差异有统计学意义(P0.05)；用药组与模型组比较,TGF-β1、Smad2、 Smad3 mRNA的表达下调,Smad7 mRNA均表达上调,差异有统计学意义(P0.05)。结论(1)清热利湿法能够有效改善支气管哮喘患儿的临床症状,不论在改善气道阻塞方面还是改善湿热症状体征方面,均具有较好的效果,并且疗效优于孟鲁司特钠,且无不良反应。(2)本研究采用OVA注射、雾化与氢氧化铝佐剂共同诱导建立哮喘大鼠模型,本模型配方简单,操作易行,经济实惠,且与人类哮喘疾病的发生、发展病理类似。(3)清热利湿法能改善哮喘大鼠一般状态,肺脏病理情况以及减少BALF中炎症细胞,减轻气道壁增厚,面积增大,从而有效地抑制哮喘的气道炎症。(4)清热利湿法通过抑制TGF-β1/Smads信号通路可阻止或减轻支气管哮喘的气道重塑,可能是其治疗支气管哮喘的重要作用机制之一。(5)清热利湿法对支气管哮喘有较好的防治作用,可作为中医药治疗支气管哮喘的基本法则之一,为临床应用提供了可靠的临床和实验依据。
[Abstract]:Through clinical research and experimental research, this paper discusses the understanding of bronchial asthma and the effect and mechanism of traditional Chinese medicine in the treatment of this disease, and to provide a reliable clinical and experimental basis for the better treatment of asthma in the future, and to prevent the further development of refractory asthma, as well as the development of new drugs of traditional Chinese medicine. It is divided into three parts. 1 literature review: through the literature review of domestic and foreign literature in recent years, the study on the attribution of the name of the Chinese medicine, the pathogenesis, the principle of treatment, the treatment of syndrome differentiation and the role of the TGF- beta 1/Smads signaling pathway in the airway remodeling of bronchial asthma, the objective observation of the clinical study on the treatment of bronchial asthma by.2 The clinical effect of the treatment of bronchial asthma with clearing heat and wet method. Methods 34 children with asthma were included in this study, including 17 cases of traditional Chinese medicine and 17 cases in western medicine group. The clinical symptoms of the children were observed before and after treatment, and the symptoms were observed before and after treatment. The results (1) there were no significant differences between the groups of children in sex, age and pre treatment. (2) the results of P0.05 were comparable. (2) the results of this study showed that 17 cases of Chinese medicine group were compared with the clinical curative effect, including 7 cases, 6 effective, 4 effective and 0 invalid. Rate 100%: 17 cases in the western medicine group, clinical cure 1 cases, effective 5 cases, effective 6 cases and invalid 5 cases, the total effective rate 70.59%. was analyzed statistically, the recovery rate and total effective rate of Chinese medicine group were better than the western medicine group, which showed that the curative effect of traditional Chinese medicine for damp and hot asthma was better. (3) from the TCM syndrome score, the total integral before and after the treatment of two groups were obviously improved. The comparison has significant statistical significance, suggesting that the two groups can effectively control the main syndrome of asthma, and the curative effect of the Chinese medicine group is better than that of the western medicine group. The secondary syndrome scores of the Chinese medicine group and the western medicine group have significant difference before and after the treatment, and the P is 0.001. It shows that the secondary syndromes of the two groups are alleviated, but the effect of the secondary TCM group is better, indicating that the effect of the secondary syndromes is better. The treatment of syndrome differentiation of medicine has a good effect on the damp and hot symptoms of damp heat asthma, and the improvement of the symptoms of damp heat is directly related to the curative effect of the whole course of the disease. (4) the curative effect of the treatment of bronchial asthma by the clearing heat and wet method is significant, and the objective of the experimental study on the treatment of bronchial asthma by.3 clearing heat and humid method (1) from the overall animal level The therapeutic effect of "Artemisia Artemisia Decoction plus subtraction prescription" on bronchial asthma and its improvement on airway remodeling; (2) the molecular mechanism of the intervention of the TGF- beta 1/Smads signaling pathway to the interference of the gene and protein level on the airway remodeling of bronchial asthma was investigated. Method (1) the study of pharmacodynamics was used to dissolve ovalbumin and aluminum hydroxide. The rat model of bronchial asthma was prepared by liquid injection and atomization. Each group was given the intervention of Artemisia Artemisia Decoction plus subtraction and dexamethasone. The normal group and the model group were given the same amount of saline intervention. After 4 weeks of treatment, the rats were killed and the serum and lung tissues were left. The general state of the rats, the pathological changes of lungs and the alveoli were observed in each group. The changes in inflammatory cells (BALF), the area and thickness of the airway wall. (2) the study of TGF- beta 1/Smads signaling pathway was used to prepare the rat model of bronchial asthma by injection of ovalbumin and aluminum hydroxide solution and atomization. Each group was given the intervention of Yin Chen Artemisia Decoction and dexamethasone, the normal group and the model. The group was given equal amount of saline intervention. After 4 weeks of treatment, the rats were killed and the serum and lung tissues were left. The protein expression of type I collagen, type III collagen, Smad2, Smad3, Smad7 and the expression of TGF- beta 1, Smad2, Smad3, Smad7 mRNA in lung tissue were expressed in lung tissue. Results (1) pulmonary tissue pathomorphology: model group lung inflammation, edema degree was more than normal group Compared with the model group, the drug groups were improved. (2) the cell deposition smear in BALF: the inflammatory cells in the model group were significantly higher than those in the normal group. Compared with the model group, the inflammatory cells in each group decreased obviously. (3) the expression level of TGF- beta 1 in BALF: compared with the normal group, the serum of the model group and the level of TGF- beta 1 expression in the model group increased, and the difference was poor. The difference was significant (P0.05), while the drug group was lower than the model group (P0.05). (4) the protein expression of type I collagen, type III collagen, Smad2, Smad3, Smad7 in lung tissue: the protein expression of type I collagen, type III collagen, Smad2, Smad3 in the lung tissue of the model group and the protein expression of Smad7 was statistically significant (P0.05) compared with the normal group (P0.05); the drug group and the model group were different. The protein expression of type I collagen, type III collagen, Smad2, Smad3 was down regulated and the expression of Smad7 protein was up regulated (P0.05). (5) the expression of TGF- beta 1, Smad2, Smad3, Smad7 mRNA in lung tissue. The expression of TGF- beta 1, Smad2, Smad3 expressions up regulated in the lung tissue of the model group, and the difference was statistically significant compared with the normal group. Study significance (P0.05); compared with the model group, the expression of TGF- beta 1, Smad2, Smad3 mRNA was down regulated, Smad7 mRNA was up regulated, and the difference was statistically significant (P0.05). Conclusion (1) the clinical symptoms of children with bronchial asthma can be effectively improved by clearing heat and humid method, both in improving airway obstruction and in improving the signs of damp and heat symptoms, all It has better effect and better effect than montelukast sodium and no adverse reaction. (2) this study uses OVA injection, atomization and aluminum hydroxide adjuvant inducement to establish the model of asthma rats. This model is simple, easy to operate and economical, and is similar to the occurrence of human asthma disease and development pathology. (3) clearing heat and wet method can improve asthma. The general state of the rats, the pathological condition of the lungs, the reduction of the inflammatory cells in BALF, the reduction of the thickening of the airway wall, the increase of the area, and the effective inhibition of the airway inflammation of the asthma. (4) by inhibiting or alleviating the airway remodeling of bronchial asthma by inhibiting the TGF- beta 1/Smads signaling pathway, the clearing and heat clearing method may be an important role in the treatment of bronchial asthma. It is one of the mechanisms. (5) the clearing heat and wet method has a good effect on the prevention and treatment of bronchial asthma. It can be used as one of the basic principles for the treatment of bronchial asthma in traditional Chinese medicine. It provides a reliable clinical and experimental basis for clinical application.

【学位授予单位】：北京中医药大学
【学位级别】：博士
【学位授予年份】：2015
【分类号】：R272

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