心律不整和自主神經系統失衡與類風溼性關節炎之探討

Cardiac Pro-arrhythmic Risks and Autonomic Nerve Dysfunction in Collagen-induced Arthritis Rats

吳志恩(Chih-En Wu)

指導教授 ： 林顯豐

國立交通大學/資訊學院/生醫工程研究所/碩士(2017年)

摘要

類風溼性關節炎是一種常見的慢性發炎反應，每個人大約有1%的機率罹患此疾病。近年來許多研究發現類風濕性關節炎患者，其心血管疾病罹患率是一般族群的兩倍，其中也包含了猝死。臨床上propranolol被廣泛用來預防心血管疾病，像是心律不整。這篇論文主要的目的為探討自主神經失衡和心臟電生理與關節炎動物模型以及propranolol之關係。我們將Lewis大鼠分為三組：對照組(Con; n=9)，collagen-induced arthritis組(CIA; n=9)和CIA treated with propranolol組(CIA-PRO; n=9)。我們會以灌食的方式餵CIA大鼠Propranolol，每周三次，每周紀錄lead II之心電圖一次進行心律變異度之分析，我們還會利用vagal/beta blocker評估自主神經系統的活性以及利用optical mapping這項技術來檢測心臟組織的表面電生理，最後我們會利用Masson trichrome 的染色來觀察CIA大鼠的心臟組織是否有纖維化。這篇論文呈現了自主神經系統活性在時間上的變化，關節炎大鼠的發炎程度以及關節炎對心臟電生理之變化。首先我們在CIA-Pro大鼠這個組別中發現了關節發炎程度有減緩的現象，可能是因為透過propranolol這個藥物減少了自主神經的失衡所得到的結果，同時我們也在CIA大鼠這個組別中發現了因inflammatory reflex所造成自主神經系統過度活化的現象，另外在CIA大鼠中我們發現了動作電位延長以及傳導速度延遲，其可能原因為發炎細胞因子對心臟電生理所造成的影響，不僅如此，我們還在CIA大鼠中發現了APD restitution curve的斜率比CIA-Pro大鼠還陡峭，這也代表了CIA大鼠發生心室震顫的機率較高。再者，我們在CIA大鼠以及對照組中並沒有觀察到任何的纖維化，可能原因為我們所建立的動物模型為初次注射Type II collagen，所以此模型為急性的類風溼性關節炎。

關鍵字

類風溼性關節炎 ； 心律不整 ； 自主神經系統失衡

並列摘要

Rheumatoid arthritis (RA) is a common autoimmune disease effecting approximately 1 % of the general population. It will not only cause joint pain and swelling but other effects in RA patients, such as an increased risk for cardiovascular disease (CVD). Clinically, propranolol is widely used to prevent cardiovascular disease, such as arrhythmia. The aim of this study is to test the associated with autonomic nervous system (ANS) dysfunction and cardiac function in RA animal model and propranolol. Lewis rats were divided into 3 groups, normal rats (Con; n=9), collagen-induced arthritis (CIA; n=9) and CIA treated with propranolol (CIA-PRO; n=9). Propranolol was used to treat with oral gavage three times a week in CIA rats. We recorded lead II ECG once a week. We also evaluated the ANS activity and cardiac electrophysiology of the heart tissue by heart rate variability (HRV), heart rate response by vagal/beta blocker and optical mapping system. Finally, we assessed the fibrosis of the heart tissue by Masson trichrome staining. This study demonstrated that the temporal change of ANS activity by using HRV analysis and heart rate response by vagal/beta blocker; severity of the rheumatoid arthritis; cardiac electrophysiology change in CIA rats. In CIA-Pro group, propranolol might remission the inflammation in CIA rats by balancing the ANS. Moreover, the sympathetic over-activity in CIA rats may cause by inflammatory reflex. Furthermore, the APD prolongation and CV delay of cardiac electrophysiology in CIA rats, which directly effects of inflammatory cytokines on cardiac electrophysiology. Slope of APD restitution curve in CIA rats were steeper than CIA-Pro rats, which could resulting in ventricular fibrillation. There were no fibrosis in CIA rats and healthy rats. Collagen was first time injected in our rats, which may indicated the acute phase of rheumatoid arthritis.

並列關鍵字

Rheumatoid arthritis ； Pro-arrhythmic risks ； ANS dysfunction

參考文獻

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