臺灣博碩士論文加值系統

動脈粥狀硬化(Atherosclerosis)是一種多因子造成的慢性血管疾病,
主要病變表現包括:血管壁內膜增厚、脂質沉積、 結蒂組織增生等。臨床
上常見動脈粥狀硬化併發冠狀動脈血管疾病,腦血管疾病,主動脈血管病變
和周邊血液循環障礙。然而,直到現在動脈粥狀硬化的致病機制仍尚未十
分明瞭。根據許多實驗的觀察,體液性免疫反應(HumorlImmunity)和細胞
性免疫反應(Cellular Immunity)被認為可能參與動脈粥狀硬化的致病機
制中。本篇論文主旨在探討免疫細胞在動脈粥狀硬化的致病機制中可能之
角色。針對這個主題,實驗分成兩部份來進行:在第一部份,利用主動脈瘤
(Aortic Aneurysm)病患進行外科手術治療時取得完整構造之主動脈血管
壁片段作為實驗材料,從組織學染色法觀察取得之主動脈血管壁片段,證實
具有完整的血管壁構造合併後期動脈粥狀硬化病變,並有不同程度的發炎
細胞浸潤現象存在血管壁中膜和外膜。間接螢光染色法觀察到有CD3陽性
T淋巴球存在這些發炎細胞中。利用高敏感性的反轉錄-聚合連鎖反應(
Reverse Transcription-PolymeraseChain Reaction)分析這些浸潤性T淋
巴球攜帶的T細胞接受體(T Cell Receptor,簡稱 TCR).BETA.鏈可變異區(
Variable Region Of .BETA. Chain),其基因表現呈多源性。將同一病患
病變血管內的浸潤性T淋巴球和血液中T淋巴球作比較,兩者在T細胞接受體
.BETA.鏈可變異區的基因表現無明顯差異。此外,比較病患組和正常組血
液中的T淋巴球,兩者在T細胞接受體.BETA.鏈可變異區的基因表現也無明
顯差異。在第二部份,我們使用E型脂蛋白元基因去除的老鼠(Apolipo-
protein E-Gene-Knockout Mouse)作為研究動脈粥狀硬化的動物模式,我
們的結果顯示,在這種老鼠的主動脈可以觀察到各種時期的動脈粥狀硬化
病變,此外,對抗氧化低密度脂蛋白(Oxidized LDL)的自體抗體也可以在其
血清內測得。利用高敏感性的反轉錄-聚合 連鎖反應分析細胞激素(Cy-
tokines)在不同組織的表現,這些表現動脈粥狀硬化病變的主動脈可以偵
測到.gamma.型干擾素(Interferon-.gamma.)和第十二介白質(Interleu-
kin-12)的基因表現。最後,由原位雜合反應(in situ Hybridization)分
析進一步顯示第十二介白質的訊息核醣核酸表現定位在動脈粥狀硬化病變
內的泡沫細胞(Foam Cells)。

Atherosclerosis is a chronic and multifactorial process commen-
cing during childhood and becoming clinically manifest later in
life. The atherosclerotic lrsion is characterized by intima thi-
ckening,lipid accumulation,and increase in connective disease,
and disease of the aorta and peripheral arterial circulation.
Nevertheless,the pathogenesis of atherosclerosis is still not
yet fully understood.Serveral lines of evidence have suggest
that both humoral and cellular immunity are involved in athor-
genesis of atherosclerosis,the present study was divided into
two parts:In part I,study was conducted using fresh samples of
human aortic aneurysm obtained from patients during surgery.His-
tological examination confirmed the presence of advanced athero-
sclerosis associated with variable aortic adventitial chronic
inflammatory cell infiltrates.Indirect immunofluorescent stain-
ing was performed to identify the CD3 T lymphocytes present in
aortic media and adventitia.Using highly sensitive transcription
-polymerase chain reaction (RT-PCR) amplification method,the T
cell receptor(TCR)V.beta.gene expression in the adventitial in-
filtrates of aortic aneurysm was shown to be polyclonal,and no
compartmentalized TCR V.beta.gene usage was observed in the in-
filtrates.In addition,the preferential utilization of any TCR V
.BETA.gene expression in the blood of aneurysmal patients was
also not observed compared with that in normal individuals.In
part II,the apoE-knockout mice was used as a murine model of
atherosclerosis for the study.It was shown that different sta-
ges of atherosclerotic lesions were found throughout aorta,and
autoantibodies against oxidized LDL were present in circulation
of the animals.By RT-PCR analysis,both mRNAs encoding IFN-.gamma
.and IL-12p40 were detected in aorta with atherosclerosis.Fur-
thermore,the expression of IL-12p40 mRNA was localized within
foam cells in atherosclerotic lesions by in situ hybridization
analysis.