以定量蛋白質體學方法分析靜脈曲張的蛋白質表現量

Quantitative proteomics analysis of varicose veins

黃琬婷(Wan-Ting Huang)

指導教授 ： 梁世欣

高雄醫學大學/生命科學院/生物科技學系碩士班/碩士(2014年)

https://doi.org/10.6832/KMU.2014.00115

摘要

靜脈曲張的形成與表淺靜脈壁的薄弱相關，薄弱的管壁會使血管逐漸失去彈性，進而導致靜脈的延展及擴張。延展的靜脈為了適應原本既有的空間，會在皮膚下變得蜿蜒甚至隆起，且靜脈的擴張也會造成靜脈瓣膜的分離，此即為靜脈曲張的成因。然而，靜脈曲張只好發於某些個體的原因以及其導致血管收縮力改變的分子機制仍未明瞭。儘管形態學、病理學和解剖學早已深入探討靜脈曲張異常表現的相關機制，但目前尚未有對於導致血管平滑肌收縮力降低的靜脈蛋白質的定量蛋白質體學研究。因此，本篇論文透過散彈槍蛋白質體分析法，以穩定性同位素二甲基標定和奈升級液相層析串聯式質譜儀分析靜脈曲張組織及其鄰近正常血管組織的蛋白質的表現圖譜。研究結果顯示肌動蛋白聚合訊息傳遞路徑相關的7個蛋白質，包含alpha-actinin-1、talin-1、myosin-11、filamin-A、vinculin、myosin light chain kinase和 profilin-1，其表現量皆呈現下降趨勢。根據研究結果，我們推測肌動蛋白聚合反應的降低可能是引起血管平滑肌功能失調，繼而形成靜脈曲張的原因之一。

關鍵字

奈升級液相層析串聯式質譜儀 ； 定量蛋白質體學 ； 散彈槍分析法 ； 穩定性同位素二甲基標定 ； 靜脈曲張

並列摘要

The weakness of vein walls of superficial veins is the main problem that may result in varicose veins. When the vein walls become weak, they will lose their elasticity, and lead to elongation and widening of the veins. Because of the elongation of veins, they get convoluted and even bulged beneath the skin for fitting the space they originally occupied. On the other hand, the widening of veins causes the valve cusps to separate. These are the reasons that bring about varicose veins. However, the reason why varicose veins occur in some individuals but not others and the molecular mechanism of altered vascular contractility remains enigmatic. Despite the fact that many investigations on the morphological, pathological and anatomical analysis underlying the abnormalities of varicose veins have been conducted, quantitative proteomics study of venous proteins that leads to decreased contractility of vascular smooth muscle have not been reported. Therefore, in this study we aim to investigate the protein expression profile in varicose veins using shotgun proteomic approach by stable isotope dimethyl labeling coupled with nanoLC—MS/MS. Our results showed that 7 proteins including alpha-actinin-1, talin-1, myosin-11, filamin-A, vinculin, myosin light chain kinase and profilin-1 involved in actin cytoskeleton signaling pathway were down-regulated. As mentioned above, the pathway indicates that defects of cytoskeletal assembly may partially lead to the dysfunction of vascular smooth muscle and the subsequent formation of varicose veins.

並列關鍵字

NanoLC-MS/MS ； Quantitative proteomics ； Shotgun analysis ； Stable isotope dimethyl labeling ； Varicose veins

參考文獻

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