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系統識別號 U0026-1102201221075100
論文名稱(中文) 運動誘發孤獨核之熱休克蛋白72改善第一型糖尿病鼠在內毒血症時之血液動力學功能
論文名稱(英文) Exercise-induced Heat Shock Protein 72 in the NTS improves Hemodynamic Function during Endotoxemia in Type I Diabetic Rats
校院名稱 成功大學
系所名稱(中) 物理治療研究所
系所名稱(英) Department of Physical Therapy
學年度 100
學期 1
出版年 101
研究生(中文) 韋雨蕾
研究生(英文) Yu-Lei Wei
學號 T66985029
學位類別 碩士
語文別 英文
論文頁數 33頁
口試委員 指導教授-洪菁霞
口試委員-劉彥青
口試委員-陳郁文
中文關鍵字 糖尿病  運動  孤獨核  熱休克蛋白72  反義股熱休克蛋白72寡核甘酸 
英文關鍵字 diabetes  exercise  NTS  HSP72  antisense HSP72 oligonucleotide 
學科別分類
中文摘要 背景與目的:糖尿病是臨床常見的代謝性慢性疾病。糖尿病患常伴隨有大、小血管的病變等嚴重併發症的危險性。臨床上常見糖尿病患傷口癒合不良,容易受到感染導致內毒血症,會伴隨全身性發炎與體內組織受破壞等現象。先前的研究透過動物實驗發現,運動訓練可以誘發大鼠心臟及孤獨核區域產生一種保護性的熱休克蛋白72 (HSP72),對於內毒血症後之組織破損有保護的效果,並改善心血管功能。本研究目的乃是在探討運動訓練後第一型糖尿病鼠腦部孤獨核熱休克蛋白72的表現量對於內毒血症時血液動力學功能的影響。方法:將八週大雄性Wistar大鼠誘發糖尿病後,分為靜態組、運動訓練組、和給予反義股HSP72寡核甘酸之運動訓練組。給予反義股HSP72寡核甘酸之運動訓練組,在誘發糖尿病前會先在頭部側腦室位置埋入注射管子,每週以微量注射方式將反義股HSP72寡核甘酸(antisense HSP 72 oligonucleotide)注射到側腦室內,使其抑制腦內熱休克蛋白72的合成。所有的運動訓練組將在經過五天的適應期後,進行為期四週的漸進式跑步機運動訓練,劑量為每週五次,每日20-60分鐘,速度為每分鐘15-21公尺。於最後一次運動訓練後24小時,取下腦部組織,利用西方墨點法(Western blotting)確認腦部孤獨核區域中HSP72的表現量。另外,在注射LPS誘發內毒血症後紀錄動物死亡時間及死亡率,並且比較各組間血液動力學參數的變化,抽取血液並監測血清中的發炎因子。結果:運動訓練組在四週的運動訓練後,延腦背側區之孤獨核的熱休克蛋白72表現量和靜態組相比有明顯增加。然而比較兩組運動訓練組,在側腦室給予反義股HSP70寡核甘酸之組別,腦部各區的熱休克蛋白皆有被抑制的趨勢。在誘發內毒血症後,運動訓練能延長動物的存活時間,然而利用反義股HSP72寡核甘酸抑制孤獨核的熱休克蛋白72表現量後,動物存活時間有減少的現象。此外,運動訓練減緩代表心血管功能之血液動力學參數 (例如心率、平均動脈壓、心輸出量、心搏量、心輸出量指數及心搏量指數)下降的速度,在給予反義股HSP70寡核甘酸之組別則比運動訓練組下降得明顯且快速。在發炎因子的測定方面,我們沒有監測到運動訓練組發炎因子下降的情況。結論:本研究提供一個直接的證據,發現給予糖尿病鼠規律的漸進式運動訓練後,能增加腦部孤獨核的熱休克蛋白72表現量,進而在內毒血症後對心血管系統功能產生維持的效果。
英文摘要 Objectives: Diabetes mellitus (DM) is an important metabolic disease worldwide, and it causes many complications, such as micro- and macro- vascular diseases. Also, diabetes may give rise to present with difficulty healing ischemic ulcer, and increases the risk of infections and developing endotoxemia. It may lead to systemic inflammatory and tissue injury. The previous study found that exercise could induce higher expression of heat shock protein 72 (HSP72) in the heart and the nucleus tractus solitarii (NTS), reduce organ damage, and attenuate cardiac dysfunction following endotoxemia. The purpose of this study is to evaluate the role of HSP72 in the protection against endotoxin-induced hemodynamic dysfunction. Methods: The diabetic rats were randomly assigned to sedentary group, exercise group, and HSP72 antisense with exercise group. The rats in antisense with exercise group received antisense HSP72 oligonucleotide by the intracerebroventricular (ICV) injection once per week. The trained rats ran on treadmill 5days/week, 20-60min/day, at the intensity of 15-21 m/min for 4 weeks. Western blotting was used to analyze HPS72 expression at 24 hours after the last training session. In addition, we recorded the survival time and the survival rate. Then we compared the changes of hemodynamic parameters and evaluated the inflammatory cytokines in rats after systemic administration of lipopolysaccharide. Results: We found that the expression of HSP72 in the NTS was increased in exercise training group. And, lower HSP72 expression in the NTS was found in antisense with exercise group. After LPS injection, the survival time of exercise rats was significantly longer than that of sedentary rats. However, the survival time of antisense with exercise group was obviously shorter than exercise group. Furthermore, the values of hemodynamic parameters (HR, MAP, CO, SV, CI, and SVI) in exercise rats were reduced more slowly than those of sedentary rats and antisense with exercise group. Additionally, there are no significant differences in serum pro-inflammatory cytokines level among these three groups. Conclusions: These data showed that regular exercise training may increase HSP72 expression in the NTS and conferred protection against endotoxemia-induced hemodynamic dysfunction in diabetic rats.
論文目次 Abbreviations--------------------------------- Ⅰ
Abstract-------------------------------------- Ⅱ
中文摘要--------------------------------------- Ⅳ
致謝------------------------------------------ Ⅵ
List of figures------------------------------ Ⅷ
Introduction--------------------------------- 1
Materials and methods------------------------ 4
Results-------------------------------------- 13
Discussion----------------------------------- 15
References----------------------------------- 18
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