【作者】 张晶晶；

【导师】 夏天；

【作者基本信息】 天津医科大学 ， 内科学， 2008， 硕士

【摘要】 背景和目的:内皮素-1(ET-1)是一种小分子生物活性物质,除了具有很强的收缩血管作用外,还可以促进细胞外基质的合成,在多种器官的纤维化中发挥重要的作用。ET-1的受体有两种,分别为内皮素受体A(ETAR)、内皮素受体B(ETBR),ET-1是通过和其受体的结合而发挥作用的。本实验通过建立模拟持续性非卧床式腹膜透析(CAPD)大鼠模型,测定不同浓度腹膜透析液组大鼠腹膜ET-1、ETAR、ETBR、以及纤维连接蛋白(FN)的表达水平,分析ET-1、ETAR、ETBR与FN的相关性,探讨CAPD相关性腹膜纤维化的发生机制。方法:S-D雄性大鼠40只(体重280g～350g),按体重分层随机分为四组,每组10只。正常对照组、1.5%腹膜透析液组、2.5%腹膜透析液组、4.25%腹膜透析液组。除正常对照组外分别给予大鼠腹腔注射不同浓度的腹透液,20ml/d,连续四周,第29天注射20ml入腹腔保留4小时后处死大鼠。免疫组化法检测壁层腹膜ET-1、ETAR、ETBR、FN的表达。结果:1.各腹膜透析液组ET-1、ETAR、ETBR、FN的表达水平与正常对照组相比较,均具有显著性差异(P＜0.05)。4.25%腹膜透析液组ET-1、ETAR、ETBR、FN的表达水平最高,2.5%腹膜透析液组又高于1.5%腹膜透析液组;2.4.25%腹膜透析液组ET-1、ETAR、ETBR的表达水平和1.5%、2.5%腹膜透析液组相比,均具有显著性差异(P＜0.05),2.5%腹膜透析液组ET-1、ETAR、ETBR的表达水平和1.5%腹膜透析液组相比,均无显著性差异(P＞0.05);3.1.5%、2.5%、4.25%腹膜透析液组FN的表达水平相比均具有显著性差异(P＜0.05)。4.大鼠腹膜间皮细胞ET-1、ETAR、ETBR的表达和腹膜FN的表达呈正相关(r=0.960,p＜0.01;r=0.908,p＜0.01;r=0.934,p＜0.01)。结论:1.腹透液可以导致大鼠腹膜问皮细胞ET-1、ETAR、ETBR、以及腹膜FN表达水平的升高,且随着葡萄糖浓度的升高而升高。2.腹膜FN的水平和腹膜间皮细胞ET-1、ETAR、ETBR的水平呈正相关,提示FN的堆积和ET-1、ETAR、ETBR的升高有关,故推断ET-1、ETAR、ETBR的升高可能是CAPD相关性腹膜纤维化的原因之一。3.高糖引起ET-1、ETAR、ETBR的升高是高糖导致FN升高的原因之一。更多还原

【Abstract】 Objections:Endothelin -1(ET-1),a 21-amino peptide hormone,has potent vasoconstrictor activity which also induces production of extracellular matrix proteins and involves in fibrotic processes of numerous organs.These ET-1 effects are elicited through the activation of two receptor subtypes,ETAR and ETBR.In the present study,we detected the expressions of ET-1,ETAR,ETBR and FN in peritoneum treated with different concentrations of PDF through the rat CAPD models,and then to investigate the effect of PDF on ET-1,ETAR,ETBR,FIg and analyze the relationship of ET-1,ETAR,ETBR and FN in non-infection situations to gain a better understanding of the mechanism of CAPD related peritoneal fibrosis.Methods:Experiments were performed on 40 adult male Sprague-Dawley rats weighing between 280～350g.Rats were randomized into 4 groups randomly and received daily intraperitoneal injection of 20ml 1.5%,2.5%,4.25%PDF into the respective group for 4 weeks except the control group,on the 29th day,after a 4-hour dwell,the rats were put to death,parietal peritoneum tissue were taken to determine the ET-1,ETAR,ETBR and FN protein expression by immunohistochemistry.Results:1.The expression of ET-1,ETAR,ETBR and FN in experimental groups was higher than that of control group,and the differences were significant.The ET-1, ETAR,ETBR and FN protein expression in 4.25%group were the highest of the experimental groups,and the values of 2.5%group were higher than that of 1.5% group.2.The ET-1,ETAR and ETBR protein in 4.25%group were higher than that of 1.5%group and 2.5%group,and the differences between 4.25%group with 2.5%group,4.25%group with 1.5%group were statistically significant(P＜0.05), but the differences between 2.5%group with 1.5%group had no statistic significance(P＞0.05).3.The FN protein expression in 4.25%group were higher than that of 2.5%group, and the values of 2.5%group were higher than that of 1.5%group,and the differences of the 3 groups had statistic significance(P＜0.05).4.There were positive correlations between expression of ET-lor ETAR or ETBR and FN(r=0.960,p＜0.01;r=0.908,p＜0.01;r=0.934,p＜0.01).Conclusion:1.PDF could induced the increase of ET-1,ETAR,ETBR and FN protein expression of CAPD rat peritoneum,and the increase followed by the increase of glucose concentrations of PDF.2.Accumulation of FN was associated with the increase expression of ET-1, ETAR and ETBR,so we can conclude that the increase expression of ET-1, ETAR and ETBR may be one of the reasons for CAPD relative peritoneal fibrosis.3.The increased expression of ET-1,ETAR and ETBR induced by glucose may be one of the reasons that glucose induce FN incresing.更多还原