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糖尿病相關(guān)勃起障礙治療分子靶標(biāo)篩選
點(diǎn)擊次數(shù)：570 發(fā)布時(shí)間：2015-6-15
勃起功能障礙是男性zui常見的糖尿病引起的并發(fā)癥之一，目前評(píng)估表明，多達(dá)75％的男性糖尿病患者會(huì)有一定程度的勃起功能障礙，而且在許多病例中糖尿病患者會(huì)有更嚴(yán)重的勃起功能障礙，對(duì)常用勃起藥物反應(yīng)較差。
細(xì)胞分析蛋白組學(xué)三月份有篇研究報(bào)道，來自凱斯西儲(chǔ)大學(xué)和阿爾伯特愛因斯坦醫(yī)學(xué)院的研究人員證實(shí)隨著糖尿病誘發(fā)ED的發(fā)生，出現(xiàn)了分子的改變，這可以作為幫助確認(rèn)ED風(fēng)險(xiǎn)的標(biāo)記以及作為潛在的藥物靶點(diǎn)。
Mark Chance和他的同事們應(yīng)用蛋白組學(xué)方法檢測(cè)糖尿病大鼠兩個(gè)不同發(fā)展階段體內(nèi)蛋白質(zhì)的相對(duì)量（勃起時(shí)充血陰莖增大的組織）：患糖尿病后的一周和兩個(gè)月。將這些大鼠與作為對(duì)照的相同年齡的健康大鼠進(jìn)行比較，確定糖尿病大鼠的陰莖組織中有57種蛋白質(zhì)增高或降低。
選擇的蛋白揭示了ED的機(jī)理，不出所料的是，糖尿病患者的膠原蛋白（給組織提供強(qiáng)度和硬度）以及運(yùn)輸性激素的蛋白也許會(huì)下調(diào)。同時(shí)，包含在凋亡細(xì)胞中的蛋白質(zhì)上調(diào)，同樣還有許多與脂肪新陳代謝有關(guān)的蛋白質(zhì)，這些改變可能與血管的縮小和硬化有關(guān)。
Mark Chance和他的同事們指出，他們研究所用的動(dòng)物模型模擬了很多人類勃起功能障礙相關(guān)的特征，因此，鑒定這57種候選蛋白可以對(duì)人類糖尿病和勃起功能障礙之間的關(guān)系做進(jìn)一步的闡釋以及更詳細(xì)的研究，并獲得對(duì)疾病的診斷和研究出藥物靶點(diǎn)。
Identifying Molecular Targets for Diabetes-Related Erectile Dysfunction
Erectile dysfunction is one of the most prevalent diabetes-induced complications in men; current estimates suggest that as many as 75% of men with diabetes will develop some degree of erectile dysfunction, and in many cases diabetics develop more severe forms of ED that are less responsive to standard drugs.
Now, in a study appearing in the March Molecular and Cellular Proteomics, researchers at Case Western Reserve University and Albert Einstein College of Medicine have identified some of the molecular changes that accompany the onset of diabetes-induced ED, which may lead to markers that will help identify ED risk as well as new potential drug targets.
Mark Chance and colleagues used a proteomics approach to examine the relative abundance of proteins in the corpora (the expandable tissues along the length of the penis which fill with blood during erection) of diabetic rats at two different stages of progression: one week and two months after the onset of diabetes. By comparing these rats to healthy age-matched controls, they identified 57 proteins in the penile tissue that either increased or decreased during diabetes.
The candidate proteins revealed insights into the mechanics of ED; perhaps not surprisingly, collagen proteins that provide strength and stiffness were down-regulated in diabetes, as were proteins that transport sex hormones. Meanwhile, proteins involved in cell death (apoptosis) were up-regulated, as were many proteins related to fat metabolism, changes that might be related to narrowing or hardening of blood vessels.
Chance and colleagues note that the rat model they used in the study mimics many relevant features of human ED, and thus the identification of these 57 candidate proteins could open up further and more detailed studies into the relationship between diabetes and ED in humans, and also lead to diagnostic and drug targets.