本文選題：清熱利濕法 + 茵陳蒿湯加減方��； 參考：《北京中醫(yī)藥大學》2015年博士論文

【摘要】：本課題通過臨床研究以及實驗研究的方法探討了中醫(yī)藥對支氣管哮喘的認識和中醫(yī)藥治療本病的療效及作用機理,為今后更好的治療哮喘,并防止其進一步發(fā)展為難治性哮喘,以及中藥新藥開發(fā)提供可靠臨床與實驗依據(jù)。分為三個部分進行論述：1文獻綜述通過近年的國內(nèi)外文獻資料檢索,探討了支氣管哮喘的中醫(yī)病名歸屬、病因病機、治療原則與辨證論治以及TGF-β1/Smads信號通路在支氣管哮喘氣道重塑中的作用。2清熱利濕法治療支氣管哮喘的臨床研究目的觀察清熱利濕法治療支氣管哮喘的臨床療效。方法將所有符合本研究納入標準的哮喘患兒共34例,其中中藥組17例,西藥組17例。分別予以茵陳蒿湯加減方免煎顆粒以及西藥孟魯司特鈉口服治療7天,觀察治療前后患兒的臨床癥狀、中醫(yī)證候改善情況,并進行系統(tǒng)的療效評價。結(jié)果(1)本臨床觀察分組患兒在性別,年齡,治療前證候積分方面比較,均無明顯差異,P0.05,具有可比性。(2)本研究結(jié)果表明：從臨床療效比較,中藥組17例,其中臨床痊愈7例,顯效6例,有效4例,無效0例,總有效率100.00%：西藥組17例,臨床痊愈1例,顯效5例,有效6例,無效5例,總有效率70.59%。經(jīng)統(tǒng)計學處理分析,中藥組痊愈率和總有效率優(yōu)于西藥組,說明中藥對于濕熱哮喘的療效更好。(3)從中醫(yī)證候積分來看,兩組患者治療前后總積分均有明顯改善,比較具有顯著統(tǒng)計學意義,提示兩組均可有效控制哮喘主要證候,且中藥組療效優(yōu)于西藥組。中藥組與西藥組治療前后次要證候積分比較具有顯著性差異,P均0.001；說明兩組均次要證候減輕,但控制次要證候上中藥組效果更佳,表明中藥辨證論治對于濕熱哮喘的濕熱癥狀有很好的改善作用,而濕熱癥狀的改善直接關(guān)系整個病程的療效。(4)清熱利濕法治療支氣管哮喘療效顯著,且臨床未見不良反應(yīng)。3清熱利濕法治療支氣管哮喘的實驗研究目的(1)從整體動物水平探討“茵陳蒿湯加減方”對支氣管哮喘的治療作用及其對氣道重塑的改善作用；(2)以TGF-β1/Smads信號通路為切入點,從基因與蛋白水平探討清熱利濕法干預(yù)支氣管哮喘氣道重塑的分子機制。方法(1)藥效學的研究采用卵蛋白與氫氧化鋁溶液注射、霧化等綜合方法制備支氣管哮喘大鼠模型,各用藥組分別給予茵陳蒿湯加減方及地塞米松進行干預(yù),正常組及模型組給予等量生理鹽水干預(yù),治療4周后處死大鼠,留取血清和肺組織,觀察各組大鼠一般狀態(tài),肺臟病理改變,肺泡灌洗液中(BALF)炎性細胞變化,氣道壁的面積和厚度的變化。(2) TGF-β1/Smads信號通路的研究采用卵蛋白與氫氧化鋁溶液注射、霧化等綜合方法制備支氣管哮喘大鼠模型,各用藥組分別給予茵陳蒿湯加減方及地塞米松進行干預(yù),正常組及模型組給予等量生理鹽水干預(yù),治療4周后處死大鼠,留取血清和肺組織,肺組織Ⅰ型膠原、Ⅲ型膠原、Smad2、 Smad3、Smad7的蛋白表達以及肺組織TGF-β1、Smad2、Smad3、Smad7 mRNA的表達。結(jié)果(1)肺組織病理形態(tài)學：模型組肺組織炎癥、水腫程度較正常組明顯加重；與模型組相比,各用藥組則均有改善。(2)BALF中細胞沉淀涂片：模型組炎癥細胞較正常組明顯增多；與模型組相比,各用藥組炎性細胞明顯減少。(3) BALF中TGF-β1表達水平：與正常組相比,模型組血清、BALF中TGF-β1表達水平升高,差異顯著(P0.05),而用藥組較模型組則下降(P0.05)。(4)肺組織Ⅰ型膠原、Ⅲ型膠原、Smad2、Smad3、Smad7的蛋白表達：模型組肺組織中Ⅰ型膠原、Ⅲ型膠原、Smad2、Smad3的蛋白表達,Smad7的蛋白表達與正常組比較,差異有統(tǒng)計學意義(P0.05)；用藥組與模型組比較,Ⅰ型膠原、Ⅲ型膠原、Smad2、Smad3的蛋白表達下調(diào),Smad7的蛋白表達上調(diào),差異有統(tǒng)計學意義(P0.05)。(5)肺組織TGF-β1、Smad2、Smad3、Smad7 mRNA的表達。模型組肺組織中TGF-β1、Smad2、Smad3 mRNA的表達上調(diào),Smad7 mRNA的表達下調(diào)與正常組比較,差異有統(tǒng)計學意義(P0.05)；用藥組與模型組比較,TGF-β1、Smad2、 Smad3 mRNA的表達下調(diào),Smad7 mRNA均表達上調(diào),差異有統(tǒng)計學意義(P0.05)。結(jié)論(1)清熱利濕法能夠有效改善支氣管哮喘患兒的臨床癥狀,不論在改善氣道阻塞方面還是改善濕熱癥狀體征方面,均具有較好的效果,并且療效優(yōu)于孟魯司特鈉,且無不良反應(yīng)。(2)本研究采用OVA注射、霧化與氫氧化鋁佐劑共同誘導(dǎo)建立哮喘大鼠模型,本模型配方簡單,操作易行,經(jīng)濟實惠,且與人類哮喘疾病的發(fā)生、發(fā)展病理類似。(3)清熱利濕法能改善哮喘大鼠一般狀態(tài),肺臟病理情況以及減少BALF中炎癥細胞,減輕氣道壁增厚,面積增大,從而有效地抑制哮喘的氣道炎癥。(4)清熱利濕法通過抑制TGF-β1/Smads信號通路可阻止或減輕支氣管哮喘的氣道重塑,可能是其治療支氣管哮喘的重要作用機制之一。(5)清熱利濕法對支氣管哮喘有較好的防治作用,可作為中醫(yī)藥治療支氣管哮喘的基本法則之一,為臨床應(yīng)用提供了可靠的臨床和實驗依據(jù)。
[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.

【學位授予單位】：北京中醫(yī)藥大學
【學位級別】：博士
【學位授予年份】：2015
【分類號】：R272

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