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    題名: 大白鼠血管週邊脂肪組識對血管影響之新進展
    Novel vascular actions of rat aortic perivascular adipose tissue
    作者: 涂念騫;Peter Nim-Hin To
    貢獻者: 醫學院臨床醫學研究所碩士班
    關鍵詞: 週邊血管脂肪組織;血管收縮;perivascular adipose tissue;vascular contraction
    日期: 2009
    上傳時間: 2010-09-29 12:17:19 (UTC+8)
    摘要: 大白鼠血管週邊脂肪組識對血管影響之新進展

    肥胖乃長久以來影響身體健康的一個問題,肥胖已被證實與很多疾病有關,諸如高血壓、糖尿病、冠心病、心衰竭、腦中風等。今天,由於社會的進步,飲食之多元化,使肥胖在全球之比率日益俱增。基於肥胖對身體之不良影響科學界已著手研究脂肪組識細胞,他們發現脂肪細胞其實是有多功能性的,因其內之Adiponnectin可分泌脂肪激酶Adipokines,而引發出自體分泌,旁分泌及內分泌等種種作用。
    血管是控制血壓的一重要角色,血管主要包含有三層,即內層的內皮細胞層、中層的平滑肌層,以及外層的外膜層,而外膜層又往往被二到三條的週邊血管脂肪組織所圍繞著,在最近10年中,學者們紛紛提出,此等週邊血管脂肪組織,是會釋出一些未知之因子,來調節血管功能,因而與血壓有關。在大多數之研究結果認為,此等因子是有增加血管之舒張能力,而少數學者則認為有增加血管之收縮能力,此因子暫定為 是一種血管衍生舒張因子, (Adipose derived relaxing factor ADRF) 我們利用大白鼠之動脈及其週邊所黏附的脂肪組織在不同的情況下,諸如有脂肪黏附的主動脈血管環,去脂肪組織之血管環,及去脂肪組織而附加脂肪組識溶液之血管環,與不同的試劑,如苯腎上腺素 ( Phenylnephrine PE ) 氯化鉀 (Potassium Chloride KCl ) Carbocheol ( CCh )及血管收縮素Angiotensin Ⅱ Ang. Ⅱ ) 進行反應,結果顯示,不論在有黏附脂肪組織的血管環,或在脂肪組織而附加脂肪組織溶液之血管環,在與PE及 KCl 反應下,皆有增加血管收縮之作用,又當我們用 NG-Nito-L- arginine methyl ester ( L-NAME ) 來抑制內皮細胞釋放Nitie Oxide ( NO ) 後,此等收縮現象依然存在。當洗去收縮劑 ( PE 及 KCl )後,那些有黏附脂肪組織的血管環,對血管舒張之速度,又比那些去脂肪組織的血管環有明顯緩慢性作用。因此,我們暫定此等脂肪組織,會釋放一種因子,命名為『 脂肪細胞衍生因子 』 ( Adipose derived Factor ADF ) 此等因子是有提高血管收縮之能力的。
    當去脂肪組織之血管環與內皮細胞舒張作用有關之CCh 作用反應,比較其附加脂肪組織溶液之前及附加之後之變化。我們發現,在這些有附加脂肪組織溶液前之血管環,其有良好之血管舒張作用。但在附加脂肪組織溶液後,則有明顯之減低舒張作用,而此一作用反應,在洗去脂肪組織溶液後,又可回復之前之血管舒張作用,在與血管收縮素Ang. Ⅱ 作用時,發現在去脂肪組織之血管環中,那些有附加脂肪組織溶液的血管環,對血管收縮的能力,遠較那些沒有附加脂肪組織溶液的血管環為高,此外,當脂肪溶液加熱到沸點時,則會喪失其血管收縮的作用,故可假想此等脂肪組織,為一種蛋白質類之結構物,加熱後會被去自然 (De-nature) 而被破壞。
    結論,經過多次實驗所得之結果,我們發現,週邊血管脂肪組織,確實是有增加血管收縮之作用,雖然此些發現與之前之文獻報告大有出入,但在現實生活中,肥胖人士容易產生高血壓及血管之病變,則又達到一合理共識之據點。

    A novel vascular action of perivascular adipose tissue

    Obesity has been a long term problem in health. It was proved to have a high relationship to many systemic diseases, such as hypertension, diabetes mellitus, coronary vascular disease, heart failure and stroke. Large increase in the prevalence of obesity over the world have resulted largely from alterations in environmental factors that increase energy intake and reduce physical activity sedentary to lifestyle and work activities.

    To learn the pathological effect of obesity to the body, scientists studied adipose tissue cells. They found that the adipose cells have multiple functions which release adipokines to exert autocrine, paracrine and endocrine effects. Blood vessel plays an important role in blood pressure control . They consist of three main layers: The inner endothelial layer, the media smooth muscle layer and the outer adventitia layer which is also surrounded by fat tissue called perivascular adipose (fat) tissues (PVAT). In recent years, investigators have been proposed that the perivascular adipose tissue could affect vascular reactivity via releasing some unknown factors and can thus provide the regulation of blood pressure. Most of the previous studies found that the perivascular adipose tissue exerts a vessel relaxation effect and a diffusible adipose derived relaxation factor (ADRF) was thus proposed although not yet identified.. We have studied the effects of PVAT on the rat thoracic aortic artery under different conditions, such in fat - intact aortic rings, fat - denuded aortic rings, fat denude aortic rings following transfer of solution incubated with fat (fat solution) or boiled fat solution. Aorta were stimulated with phenylnephrine (PE), potassium chloride (KCl), angiotensin II (Ang II), and the carbachol (CCh). In contrast to the previously study, we found that either the in situ aortic fat or the solution incubated with isolated fat can increase contractile response in the form of enhanced sensitivity to PE and KCl. This respondes persist even after the inhibition of the endothelium nitric oxide (NO) production with NG-nitro-L arginine methyl ester (L-NAME). Upon wash out of PE and KCl, a slower relaxation rate was found in the aortic rings with intact perivascular adipose tissues. For the endothelium dependent relaxation to carbachol (CCh), it was reduced in the presence of fat pre-incubated solution and can be reversed after wash out of the fat solution. In response to Ang II, the aortic rings also showed an enhance contractile response in the upon transfer of fat pre-incubated solution. When the fat solution has been boiled, no enhance contractile response was he notion that obese people with high visceral fat content has a higher risk in developing high blood pressure and vascular complications characteristic of metabolic syndrome
    顯示於類別:[臨床醫學研究所] 博碩士論文

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