臺灣博碩士論文加值系統

在工業化的社會中，過敏性鼻炎在成人以及兒童的盛行率分別約為30%，和40%。能夠緩解過敏性鼻炎症狀的西醫藥物包括antihistamines、decongestants、leukotriene inhibitors、topical hormones以及corticosteroids。臨床上許多過敏性鼻炎患者，因為畏懼西醫藥物治療的副作用，而求助於傳統中醫藥或針灸的幫助。當把針刺入穴位內做針刺治療時，針刺經由雙向調控作用來治療疾病症狀，本論文研究針刺治療常年性過敏性鼻炎病患的治療效果。

每週進行2次針刺，在四週內總計針刺八次。然後進行周邊血液分析，以及分別用cDNA Microarray研究18位PhadiatopTM測試陽性的過敏性鼻炎病患，Affymetrix human U133A chips研究13位PhadiatopTM測試陽性的過敏性鼻炎病患與8位PhadiatopTM測試陰性的鼻炎病患，來分析針刺治療過程中的作用機轉。過程中以「鼻結膜炎生命品質調查問卷」(Rhinoconjunctivitis and Rhinitis Quality of Life Questionnaire - RQLQ)做調查與統計分析。以研究針刺過敏性鼻炎病患的臨床效果與基因表現特徵。

以cDNA Microarray研究18位過敏性鼻炎病患，結果顯示針刺對過敏性鼻炎確實具有臨床療效， RQLQ統計顯示，在睡眠、非鼻眼症狀、實際問題、鼻部症狀等類別有明顯改善，且有統計意義。針刺治療過敏性鼻炎病患前後，周邊血液基因的差別表現顯示，在針刺治療後2小時、24小時以及第八次針刺後，IL1R1是顯著性的減少。

以Affymetrix human U133A chips研究13位PhadiatopTM測試陽性的過敏性鼻炎病患與8位PhadiatopTM測試陰性的鼻炎病患，結果顯示針刺治療療後的RQLQ與基因表現特徵在Ph(+)組與Ph(-)組病患的結果是不同的。與Ph(-)組病患比較，Ph(+)組病患的RQLQ結果在活動、實際問題、鼻部症狀等類別有明顯改善，且有統計差異。針刺治療後在Ph(+)組與Ph(-)組病患的基因表現特徵所牽涉到的active immune response及differential of Treg and cell apoptosis是不同的。

據文獻顯示，本研究是第一個採用microarray，來研究針刺治療過敏性鼻炎病患前後，周邊血液總體的差異性表現基因。本研究顯示Th1細胞衍生出的pro-inflammatory cytokines與Th2細胞衍生出的anti-inflammatory cytokines其對抗平衡，將會在針刺治療後獲得改善。在針刺治療後，Ph(+)組與Ph(-)組病患間的差異性基因表現特徵，表示針刺後產生不同的生理反應。這項結果數據顯示出個人化的醫療治療(personalized medical treatment)，在針刺過敏性鼻炎病患是必須考慮的。

Allergic rhinitis affects approximately 30% of adults and up to 40% of children in industrialized societies. Medicines available for relief of allergic rhinitis symptoms include antihistamines, decongestants, leukotriene inhibitors, topical hormones and corticosteroids. However, the negative side effects of anti-allergic medicines cause many allergic rhinitis patients to choose traditional Chinese medical treatments - such as taking Chinese herbs or treatment with acupuncture. Acupuncture therapy corrects the equilibrium deviation using the bi-directional regulative actions in treating syndromes by inserting needles into acupoints. We assessed the therapeutic effect of acupuncture in perennial allergic rhinitis patients.

We studied the clinical outcomes and gene expression profiles of allergic rhinitis patients who were treated with acupuncture. The patients were treated with acupuncture eight times over a four week period and peripheral blood of these patients was collected at each visit for analysis of gene expression. Eighteen phadiatopTM positive allergic rhinitis patients were analysised by cDNA microarray, and 13 phadiatopTM positive allergic rhinitis patients with 8 phadiatopTM negative rhinitis patients were analysised by Affymetrix human U133A chips. To estimate the therapeutic effect of acupuncture objectively, patients completed the rhinoconjunctivitis quality of life questionnaire (RQLQ) before and after acupuncture therapy.

Based upon patient response to the RQLQ in cDNA microarray study, acupuncture therapy significantly improved allergic rhinitis symptoms, including nasal symptoms, non-hay fever symptoms, sleep and practical problems（daily activities）. Additionally, expression of interleukin 1 receptorα(IL1R1) in peripheral blood was significantly decreased at 2 hours, 24 hours and 4 weeks after acupuncture treatment in these patients.

In Affymetrix human U133A chips study, The results of the RQLQ and the gene expression profiles were different between the Ph(+) and Ph(-) groups after receiving treatment with acupuncture. Activity, practical problems, and nasal symptoms showed significant improvement in the Ph(+) group versus the Ph(-) group. In addition, genes involved in active immune response, differential of Treg and cell apoptosis, were different in the Ph(+) and Ph(-) groups after acupuncture treatment.

To our knowledge, this is the first report of cDNA microarray analysis of differential gene expression in the peripheral blood of allergic rhinitis patients before and after acupuncture treatment. Our data suggest that the balance between T helper 1 (Th1) and T helper 2 (Th2) cell-derived pro-inflammatory versus anti-inflammatory cytokines might be improved by acupuncture treatment.

Differential gene expression profiles of Ph(+) and Ph(-) allergic rhinitis patients indicate the distinct physiological responses after receiving acupuncture treatment in these two groups. Our results suggest that personalized medical treatment should be essential for acupuncture treatment in allergic rhinitis patients.

目錄
附表目錄 3
附圖目錄 4
中文摘要 5
英文摘要 7
第一章 緒論 9
第一節 背景及文獻回顧 9
第二節 研究目的與範疇 15
第二章 過敏性鼻炎針刺治療前後之cDNA微陣列初步分析 19
第一節 前言 19
第二節 研究方法與材料 20
第三節 結果 23
第四節 討論 27
第三章 過敏性鼻炎針刺治療前後之cDNA微陣列進一步分析 31
第一節 前言 31
第二節 研究方法與材料 34
第三節 結果 35
第四節 討論 37
第四章 過敏性鼻炎針刺治療前後之寡核酸晶片分析 43
第一節 前言 43
第二節 研究方法與材料 48
第三節 結果 55
第四節 討論 60
第五章 結論與未來展望 64
第六章 參考文獻 67
第七章 內容圖表 76

附表目錄
表 一 過敏性鼻炎患者針刺RQLQ量表統計結果 76
表二 過敏性鼻炎患者針刺前後IgE差異統計結果 77
表 三 Blood composition in patients before, during, and after acupuncture treatment 78
表 四 針刺2、24小時及4週後，與down-regulated有關的基因名稱 79
表 五 針刺2、24小時及4週後，與up-regulated有關的基因名稱 81
表 六 第八次針刺後與第一次針刺前比較為基準，down-regulated有關基因 83
表 七 第八次針刺後與第一次針刺前比較為基準，up-regulated有關基因 84
表 八 Global gene expression changes during acupuncture treatment 85
表 九 Pro-inflammatory genes with increased expression in patients after acupuncture treatment 87
表 十 patients’ RQLQ results after the 5th & 8th acupuncture (Acu) treatments 88
表 十一 Change in patients’ IgE levels after 4 weeks of acupuncture treatment 89
表 十二 Individual and pooled RNA samples 90

附圖目錄
圖 一 過敏性鼻炎受試者microarray初步結果。 91
圖 二以第一次針刺後2小時與第一次針刺前比較為排序基準 92
圖 三 以第一次針刺後24小時與第一次針刺前比較為排序基準 93
圖 四 以第八次針刺後與第一次針刺前比較為排序基準 94
圖 五 RAB (member of RAS oncogene family-like 3) 及EST clone (IMAGE: 4814010)，在17,16,19,10,13,8號受試者，隨針刺時間變化表現圖 95
圖 六 Differentially expressed genes significantly regulated by acupuncture treatment. 96
圖 七 Gene expression levels of (A) Ribosomal RNA, (B) Hemoglobin and (C) HSH2 and NOS1 at 4 time points after acupuncture treatment. 97
圖 八 Model of pro-inflammatory and anti-inflammatory actions of acupuncture. 98
圖 九 Hierarchical clustering analysis of the gene expression profiles of acupuncture treatment. 99
圖 十 Three dimension principle component analysis of the gene expression profiles of acupuncture treatment. 100
圖 十一 Differentially expressed genes significantly regulated by acupuncture treatment in Ph(+) and Ph(-) patients. 101
圖 十二 Functional networks of B group genes (see圖 十一) trigger regulatory T cell differential. 102

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