過敏性鼻炎針刺治療前後之微陣列晶片分析

DNA Microarray Analysis of the Effect in Patients Treated with Acupuncture for Allergic Rhinitis

薛宏昇(Horng-Sheng Shiue)

指導教授 ： 許準榕

共同指導教授 ： 張恒鴻

臺北醫學大學/醫學院/醫學科學研究所/博士(2009年)

https://doi.org/10.6831/TMU.2009.00016

摘要

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。

關鍵字

基因微陣列 ； 過敏性鼻炎 ； 針刺 ； 基因表現特徵 ； IL-1Rα

並列摘要

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.

並列關鍵字

cDNA microarray ； Allergic Rhinitis ； Acupuncture ； gene expression profile ； IL-1Rα

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