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研究生:陳怡臻
研究生(外文):Yi-Chen Chen
論文名稱:亞急性投予乙醇對大白鼠腦區N-甲基-D-天門冬胺酸受體活性及心血管功能之影響
論文名稱(外文):Effect of Sub-acute Administration of Ethanol on N-methyl-D-aspartic Acid Receptor Activations in the Rostral Ventrolateral Medulla (RVLM) and Cardiovascular Function in Rat
指導教授:賴志嘉賴志嘉引用關係
指導教授(外文):Chih-Chia Lai
學位類別:碩士
校院名稱:慈濟大學
系所名稱:藥理暨毒理學研究所
學門:醫藥衛生學門
學類:藥學學類
論文種類:學術論文
畢業學年度:97
語文別:英文
論文頁數:58
中文關鍵詞:酒精前腹外側延腦區血壓亞急性
外文關鍵詞:EthanolRVLMsub-acuteblood pressure
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中文摘要
由流行病學研究指出,過度飲酒容易導致酒精性心血管疾病,如高血壓。但適量的攝取酒精,卻具有保護心血管的功能。
由早期的研究已知前腹外側延腦區(RVLM)內的神經元,可調控維持血管的張力,同時也參與瞬間血壓改變時的調節作用。但酒精調控心血管功能的機轉尚未明確。
我們的研究希望能夠探討亞急性投予酒精對Sprague-Dawley (SD)母鼠心血管功能的影響。將大白鼠給予腹腔注射生理食鹽水(20 ml/kg)及酒精(3.2 g/kg)持續施打七天,並監測心跳及血壓變化。
. 此外,我們在事前先每天投予高濃度酒精(3.2 g/kg)後於第一、三、五天進行隱靜脈採血,監測其血中酒精濃度。觀察亞急性投予酒精後其血中濃度的變化程度。
本實驗結果發現,酒精會引發降壓反應並在第五天後消失,而五天內的血中酒精濃度在腹腔注射酒精後30到60 分鐘皆無明顯變化。這顯示在給予亞急性投予高濃度酒精後,心血管產生耐受性的反應,而使酒精造成的降壓作用消失。
此外,我們也發現投予酒精5天後,可能經由蛋白激酶A及蛋白激酶C路徑,使前腹外側延腦區的NMDA次單位ser897及ser896磷酸化程度增加。
因此,我們認為亞急性投予酒精後,可能經蛋白激酶A及C路徑磷酸化前腹外側延腦區的NMDA接受體,進而使酒精所造成的降壓作用消失。
英文摘要
Epidemiologic studies have shown that heavy drinking can lead to ethanol cardiovascular diseases such as hypertension. However, in moderate quantities ethanol may play a cardioprotective role.
From the early research, the neurons of RVLM could modulate the tone of blood vessel and also involve the immediate change of blood pressure. The precise mechanisms underlying ethanol regulation of cardiovascular function remains unclear. The present study determined the cardiovascular effects of sub-acute ethanol administration in female Sprague-Dawley (SD) rats. Changes in blood pressure (BP) and heart rate (HR) were evaluated in rats injected intraperitoneally (i.p.) with saline or ethanol (3.2 g/kg) for 7 days. The blood was collected from saphenous vein at various times post-injection for determination of blood ethanol concentrations.
We found that ethanol-induced depressor effect was disappeared at and after 5-day treatment. The blood ethanol levels at 30 and 60 min after injected intraperitoneally ethanol at day 5 were similar to those at day 1. The results indicate a development of cardiovascular tolerance to ethanol-induced depressor effects following sub-acute administration of higher doses of ethanol. Moreover, we found that a significant increase in the expression of the phosphoserine 896, 897 protein (regulation by PKC, PKA pathway) on GluN1 subunit in the RVLM after 5 day treatment.
The results suggest a relation between the disappearance of pressor effect and the phosphorylation of GluN1 subunit in the RVLM following sub-acute treatment of ethanol.
目錄
中文摘要 II
英文摘要 III
壹、背景介紹 1
一、乙醇 1
二、乙醇對心血管的影響 2
三、乙醇的耐受性、依賴性及戒斷作用 2
四、乙醇的代謝與性別的相關性 3
五、前腹外側延腦區(Rostral Ventrolateral Medulla)與血壓的相關性 3
六、麩胺酸鹽受體(glutamate receptor) 4
七、N-甲基-D-天門冬胺酸鹽受體(N-methyl-D-aspartic acid Receptor) 4
八、A型激酶 (Protein kinase A ) 6
九、C型激酶 (Protein kinase C ) 7
貳、研究目的與實驗設計 8
一、實驗之理論基礎 8
二、研究目的 8
三、實驗假設 9
四、實驗設計 9
參、實驗方法材料與詳細步驟 10
一、材料 10
二、實驗步驟 11
實驗一 監測血中酒精濃度 11
實驗二 活體心血管血壓心跳變化長期監測實驗(清醒鼠模式) 12
實驗三 觀察RVLM腦區的NMDA接受體活性 13
實驗四前腹外側延腦區(RVLM)定位實驗(麻醉鼠模式) 15
三 、統計方法 17
肆、實驗結果 18
探討急性與亞急性投予酒精後大白鼠血中酒精濃度變化情形 18
亞急性投予酒精對大白鼠血壓心跳之影響 19
亞急性投予酒精後,觀察前腹外側延腦區(RVLM)中NMDA受體其蛋白質及被磷酸化之程度。 20
急性與亞急性投予酒精對NMDA刺激前腹外側延腦區(RVLM)所引發升壓反應之影響(麻醉鼠模式) 21
伍、討論 22
一、探討酒精對心血管反應的影響 22
二、探討酒精對前腹外側延腦區NMDA受體活性之影響 24
三、探討酒精對前腹外側延腦區調控血壓的影響 25
四、酒精對其他受體的影響 26
陸、結論 27
柒、參考文獻 28
捌、結果附圖 35
附錄一 47
附錄二 48
附錄三 49
附錄四 50
附錄五 51
柒、參考文獻
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非SCI之文獻
林欣欣、林瑞泰:酒精對中樞神經系統的影響,高醫醫訊月刊,第二十卷,第五期,2000.
許勝雄:酒精與心臟,高醫醫訊月刊,第二十卷,第五期,2000.
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