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研究生:王耀宏
研究生(外文):Wang, Yao-Horng
論文名稱:職業暴露研究之動脈硬化之動物模式與心肌缺血前制約效應之探討
論文名稱(外文):The Animal Model of Atherosclerosis in Cholesterol-fed Swine and the Ischemic Preconditioning Effect for the Occupational Exposure Study
指導教授:賴俊雄賴俊雄引用關係
指導教授(外文):Lai Jim-Shoung
學位類別:碩士
校院名稱:中國醫藥學院
系所名稱:環境醫學研究所
學門:醫藥衛生學門
學類:公共衛生學類
論文種類:學術論文
論文出版年:1997
畢業學年度:85
語文別:中文
論文頁數:3
中文關鍵詞:動脈硬化症心肌缺血前制約效應
外文關鍵詞:AtherosclerosisIschemic Preconditional effect
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由衛生署每年公布的公共衛生概況資料中,國內十大死因中與心臟血管
疾病相關的有腦血管疾病、心臟疾病、腎炎、腎徵候群及腎病變、和高血
壓疾病,而主要致病原因以動脈硬化佔大部分。在公共衛生學或是職業暴
露研究上,對於心血管相關疾病的研究需要長時間的觀察或追蹤探討分析
,不僅浪費大量金錢與時間,所得結果往往只能做為衛生政策制定參考,
無法直接應用於臨床診斷治療之用。所以如何發展或尋找一可行且可立即
應用之心血管疾病的研究模式,為目前迫切之課題。因此為了建立心血管
疾病中動脈硬化症的動物試驗模式及探討心肌缺氧前制約效應對動脈硬化
症之影響。 24隻八週大的約克夏小公豬分為兩組,12隻餵飼正常飼料(
正常組,N.),12隻餵飼高膽固醇飼料(高膽固醇組,H.),連續飼養4個月
,每隔二週採血測量血中的各項脂質含量。4個月後,將以上二組各分為
對照組(C., N=6; H=6)與前制約效應組(IP., N=6; H=6)。以開胸手術
分離出心臟的左前下降支冠狀動脈(LAD),N.組將LAD持續綁緊60分鐘後再
鬆開120分鐘,以阻塞後再灌流的模式觀察心肌缺氧時心肌傷害的程度。
IP組乃在進行上述步驟前,先綁緊10分鐘後,再鬆開灌流30分鐘來造成前
制約效應。實驗結束後,取下心臟進行危險區域(RA)及梗塞壞死區域(IA)
比率之測量。RA以甲基藍注入左心房染色;IA以TTC
(triphenyltetrazolium chloride)染色。並採取主動脈及冠狀動脈部分
組織,以10%中性福馬林固定後,進行相關之組織病理檢查。 由結果得
知:高膽固醇組豬隻血中總膽固醇(CHL)、三酸甘油脂(TG)、高密度脂蛋
白(HDL)及低密度脂蛋白(LDL)均較正常組為高。心肌缺血試驗中:對照組
中RA/總心肌:高膽固醇組(60.3±20.3%)與正常組(57.4±18.1%)無明
顯差異(p>0.05);IP組中IA/RA:高膽固醇組(18.3±6.5%)與正常
組(17.3±7.4%)差異亦不顯著(P>0.05)。但前制約效應組中,無論是正
常組或高膽固醇組其梗塞壞死區域均較對照組為小(p<0.05),因此心肌缺
氧前制約效應確實可保護心肌,使心肌梗塞壞死區域變小,且在高膽固醇
組一樣會有保護作用,可以降低因心肌缺血所造成的損害。由病理組握薑
钀邠d結果可知:高膽固醇組於主動脈及其它動脈已造成明顯的脂肪
瘢(37.9±16.1),且血管內膜有明顯的增生;而正常組則無任何脂肪瘢或
內膜增生情形產生。 本研究結果顯示,經由高膽固醇飼料之餵飼,在豬
隻可誘發動脈硬化症。短暫的心肌缺血前制約效應,於正常組與高膽固醇
組均對心肌有保護作用。

BACKGROUND: Overwhelming evidences indicate that
hypercholesterolemia induces atherosclertic lesion at aorta or
coronary artery which causes thrombosis and leads to acute
myocardium infarction (MI). Clinically, ischemic
preconditioning (IP) can increase tolerance of myocardium to
prevent ischemic injury and reduce infarct size. However, it is
not clear that IP may have protective effect for MI in
hypercholesterolimic swine. We evaluated this hypothesis using
cholesterol-fed pigs. METHODS: 8-week-old Yorkshire swine were
fed with high cholesterol diet (2% cholesterol, 18% lard and 80%
standard diet) for 4 months (n=12, group H). For control
studies, pigs were fed with standard diet (n=12, group N).
Serum lipid profiles including cholesterol (CHL), high density
lipid cholesterol (HDL-C), triglycide (TG), and body weight were
measured. Pigs from those two groups were divided into IP (n=6)
and untreated (n=6, C) group. Open-chest procedure were
performed to dissect the left anterior descending coronary
artery (LAD). IP group was subjected to 10-min LAD occlusion
and 30-min reperfusion for preconditioning effect followed by
60-min LAD occlusion and 120-min reperfusion. group C was
subjected to only 60-min LAD occlusion followed by 120-min
reperfusion. Risk area (RA) was measured by injecting methlyene
blue into left atrium. Infarct area (IA) was stained with
triphenyltetrazolium chloride. RESULTS: Beginning from 4-week
cholesterol diet to the end of this experiment, serum lipid
profiles of Group H were higher than those of group N. There
were no statistic differences for the percentage of IA/RA
between group H and group N [IP: group H (18.3±6.5) vs. group N
(17.3±7.4); C: group H (60.3±20.3) vs. group N (57.4±18.1)].
However, significant number of fatty streaks were observed on
the surface of aorta and fewer on the surface of the LAD in
group H. CONCLUSION: Ischemia preconditioning has protective
effect on ischemic injury and, at the same time, decreases the
infarct size in cholesterol-fed and normal-diet-fed swine.

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