本文選題：支氣管哮喘　切入點：哮喘平沖劑　出處：《安徽中醫(yī)藥大學》2016年碩士論文

【摘要】：1.臨床研究1.1目的:對142例支氣管哮喘(bronchial asthma,BA)患者進行中醫(yī)證候學調查,探求哮喘中醫(yī)證候分布規(guī)律,為哮喘的中醫(yī)辨證分型和臨床治療提供理論依據。1.2方法:參考資料制定哮喘證候表,結合哮喘控制測試(ACT)評分及哮喘控制情況表,對符合條件的142例哮喘患者的資料利用統計軟件對相關因素進行分析,總結哮喘中醫(yī)證型分布規(guī)律。1.3結果:142例哮喘患者中寒哮證共有65例(所占比例45.77%),哮喘易感體質以陽虛質和痰濕質為主,分別占比35.91%和32.39%,說明哮喘的發(fā)病與體質因素相關。2.實驗研究1.1目的:觀察哮喘平沖劑對哮喘模型大鼠細胞因子IL-17、Notch信號通路的影響,探討哮喘平沖劑治療哮喘的免疫機制及分子機制。1.2方法:將84只健康雄性的SD大鼠隨機分為7組:正常對照組、哮喘模型組、潑尼松西藥組、金水寶中成藥組,哮喘平沖劑低、中、高劑量組,每組12只,常規(guī)喂養(yǎng)7天后開始造模。致敏2次,以卵蛋白(Ovalbumin,OVA)噴霧激發(fā),每日1次,共激發(fā)5周。霧化造模結束后中藥低、中、高劑量組予以哮喘平沖劑、西藥組予以潑尼松、中成藥組予以金水寶膠囊灌胃治療,正常組、模型組予以等量生理鹽水灌胃,每天一次,連續(xù)2周。其中,中藥高劑量組予以0.625g/kg/d為給藥劑量(相當于成人的12.5倍),中藥中劑量組予以0.313g/kg/d為給藥劑量(相當于成人的6.25倍),中藥低劑量組予以0.157g/kg/d為給藥劑量(相當于成人的3.13倍),西藥組予以0.313g/kg/d為給藥劑量,中成藥組予以0.313g/kg/d為給藥劑量。兩周后取材檢測血清及肺泡灌洗液IL-17的含量,免疫組化檢測Notch信號通路Notch1-4的表達,探討哮喘平沖劑對哮喘治療的機制。1.3結果:1.3.1大鼠血清IL-17含量:與正常組相比,模型組大鼠血清IL-17含量顯著高于正常組(P0.01)。與模型組相比,各治療組大鼠血清IL-17含量均降低(P0.01)。西藥組與中藥高劑量組相比,差異無統計學意義(P0.05)。中成藥組與中藥低劑量組相比,差異無統計學意義(P0.05)。中藥中劑量組、中藥高劑量組大鼠血清IL-17含量均低于中成藥組(P0.05)。1.3.2大鼠肺泡灌洗液IL-17含量:與正常組相比,模型組大鼠肺泡肺泡灌洗液IL-17含量顯著高于正常組(P0.01)。與模型組相比,各治療組大鼠肺泡肺泡灌洗液IL-17含量均降低(P0.01)。西藥組與中藥高劑量組相比,差異無統計學意義(P0.05)。中成藥組與中藥低劑量組相比,差異無統計學意義(P0.05)。中藥中劑量組、中藥高劑量組大鼠肺泡灌洗液IL-17含量均低于中成藥組(P0.05)。1.3.3免疫組化檢測各組大鼠肺組織Notch1-4表達:與正常組相比,模型組肺組織Notch1、Notch2平均光密度值顯著高于正常組(P0.01);與模型組相比,治療組各組肺組織Notch1、Notch2平均光密度值均降低(P0.01);中藥高劑量組與西藥組比較,差異無統計學意義(P0.0 5),中藥中劑量與中藥低劑量比較,Notch1、Notch2平均光密度值有所降低(P0.05);中藥低劑量與中成藥組比較,差異無統計學意義(P0.0 5)。與正常組比較,模型組Notch3平均光密度值有增高(P0.05),其余各組肺組織中Notch3平均光密度值均明顯減弱,且兩組間比較無明顯差異(P0.0 5)。Notch4平均光密度值在各組中均無明顯增高。1.3.4 RT-PCR檢測肺組織Notch1-4 mRNA表達:與正常組相比較,模型組肺組織Notch1、Notch2 m RNA表達顯著高于正常組(P0.0 1),與模型組相比較,治療組各組肺組織Notch1、Notch2 m RNA表達均降低(P0.0 5),中藥高劑量組與西藥組比較,差異無統計學意義(P0.05),中藥中劑量組Notch1、Notch2 m RNA表達較中藥低劑量組降低(P0.0 5),中藥低劑量組與中成藥組比較,差異無統計學意義(P0.0 5);Notch3 m RNA在模型組及對照組各組肺組織中表達均減弱,兩組比較無差異(P0.0 5)。Notch4m RNA在模型組肺組織及對照組肺組織中均表達不明顯。3.結論:3.1在所研究的142例哮喘患者中證型以哮喘冷哮證居多。3.2哮喘平沖劑治療哮喘的免疫機制可能是抑制白細胞介素-17(IL-17)的產生,從而減輕氣道炎癥;治療哮喘的分子機制可能是通過下調Notch信號通路中參與T細胞分化與激活的Notch1、Notch2的表達,從而延緩哮喘的氣道重塑。
[Abstract]:1. clinical research 1.1 Objective: 142 cases of bronchial asthma (bronchial asthma, BA) in patients with TCM syndrome of asthma survey, explore the distribution regularity of TCM syndromes, and provide a theoretical basis for the.1.2 method for traditional Chinese medicine syndrome type and clinical treatment of asthma: reference for asthma syndrome scale combined with asthma control test (ACT) score and asthma control table, to meet the conditions of 142 cases of patients with asthma data using statistical software to analyze the related factors, summed up the law.1.3 results of TCM syndrome of asthma distribution: 142 asthma patients in cold syndrome were found in 65 cases (accounted for 45.77%), asthma susceptible to yang deficiency and phlegm dampness, accounted for more than 35.91% and 32.39%, indicating the onset of.2. and physical experimental study on related factors of asthma 1.1 Objective: To observe the asthma Granule on asthmatic cytokines in rats with IL-17, the effect of Notch signaling on asthma The immune mechanism and the molecular mechanism of.1.2 granule in treating asthma asthma methods: 84 healthy male SD rats were randomly divided into 7 groups: normal control group, asthma model group, prednisone group, western medicine, Chinese medicine group, Jinshuibao xiaochuanping powder, low, high dose group, 12 rats in each group, routine feeding 7 days after modeling. Sensitized with ovalbumin 2 times (Ovalbumin, OVA) spray excitation, 1 times daily for 5 weeks. Total excitation is low, traditional Chinese medicine atomization after the modeling, the high dose group of xiaochuanping powder, western medicine group was given prednisone, Chinese medicine group was given Jinshuibao capsule gavage treatment and the normal group, model group were given normal saline, once a day for 2 weeks. Among them, high dose of Chinese medicine group were given 0.625g/kg/d dosage (equivalent to 12.5 times the adult), Chinese medicine dose group received 0.313g/kg/d dose (equivalent to 6.25 times a person), Chinese medicine low the 0.157g dose group /kg/d dose (equivalent to 3.13 times the adult), western medicine group received 0.313g/kg/d dose, Chinese medicine group received 0.313g/kg/d dose after two weeks. The content of serum and bronchoalveolar lavage fluid IL-17 detection, immunohistochemical detection of Notch signal pathway in the expression of Notch1-4, to investigate the xiaochuanping powder on the results the mechanism of.1.3 treatment of asthma: the content of IL-17 in serum of 1.3.1 rats: compared with normal group, the content of IL-17 in serum of rats in model group were significantly higher than the normal group (P0.01). Compared with the model group, the content of IL-17 in serum of rats in each treatment group were decreased (P0.01). Compared with the traditional Chinese medicine Western medicine group and high dose group, no significant difference meaning (P0.05). Compared with the traditional Chinese medicine group low dose group, the difference was not statistically significant (P0.05). Chinese medicine dose group, high dose of Chinese medicine group rats serum IL-17 levels were lower than the traditional Chinese medicine group (P0.05).1.3.2 in rat alveolar lavage fluid containing IL-17 Weight: compared with the normal group, model group of rat alveolar alveolar lavage fluid IL-17 was significantly higher than normal group (P0.01). Compared with the model group, the alveolar alveolar lavage fluid of rats in each treatment group IL-17 decreased (P0.01). Compared with the traditional Chinese medicine Western medicine group and high dose group, no significant difference (P0.05) compared with traditional Chinese medicine. Chinese medicine group, low dose group, the difference was not statistically significant (P0.05). Chinese medicine dose group, high dose of Chinese medicine group rat bronchoalveolar lavage fluid IL-17 levels were lower than the traditional Chinese medicine group (P0.05) immunohistochemical detection of.1.3.3 in lung tissue of rats Notch1-4 expression: compared with normal group, model group, lung tissue Notch1 Notch2, the average optical density value is significantly higher than the normal group (P0.01); compared with the model group, treatment group Notch1 lung tissue, the average optical density values of Notch2 were decreased (P0.01); high dose of Chinese medicine group and Western medicine group, the difference was not statistically significant (P0.0 5), Chinese Medicine In comparison, Chinese medicine dose and low dose of Notch1, the average optical density values of Notch2 decreased (P0.05); relatively low dose of traditional Chinese medicine and traditional Chinese medicine group, the difference was not statistically significant (P0.0 5). Compared with the normal group, Notch3 model group, the average optical density increased (P0.05), Notch3 in other groups in the lung tissues of the average light the density values were significantly decreased, and no significant difference between the two groups (P0.0 5) the average optical density values of.Notch4 in each group were not significantly higher expression of Notch1-4 mRNA in lung tissue of.1.3.4 RT-PCR: compared with the normal group, model group, lung tissue Notch1, Notch2 expression of M RNA was significantly higher than the normal group (P0.0 1). Compared with the model group, treatment group Notch1 lung tissue, the expression of Notch2 m and RNA were decreased (P0.0 5), high dose of Chinese medicine group and Western medicine group, the difference was not statistically significant (P0.05), Chinese medicine dose group Notch1, Notch2 m RNA expression compared with the low dose of Chinese medicine group Reduce (P0.0 5), compared with the low-dose group of Chinese medicine and traditional Chinese medicine group, the difference was not statistically significant (P0.0 5); the expression of Notch3 m RNA in the model group and control group in lung tissue were decreased, the two groups have no difference (P0.0 5).Notch4m expression of RNA was not obvious.3. in lung tissue of model group and conclusion the control group in the lung tissues: 3.1 immune mechanism in 142 asthmatic patients in the syndrome type of asthma with cold asthma are.3.2 xiaochuanping powder for the treatment of asthma may be the inhibition of interleukin -17 (IL-17) generation, so as to reduce airway inflammation; molecular mechanism of treating asthma may down regulate the expression of Notch1 T cell differentiation and activation of the Notch signaling pathway involved in the expression of Notch2, thus delaying the airway remodeling of asthma.

【學位授予單位】：安徽中醫(yī)藥大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R256.12

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