Caveolin-1和紧密连接蛋白在小鼠血吸虫性结肠炎中的表达及其意义

Expressions and Significances of Caveolin-1 and Tight Junction Proteins in Schistosomiasis Colitis in Mice

背景:血吸虫肠病是一种血管内寄生虫病,结肠慢性炎症是其基本的病理改变之一。目前有关caveolin-1和紧密连接蛋白参与血吸虫肠病发病的机制仍不明确。目的:初步探讨caveolin-1和紧密连接蛋白occludin、claudin-1在小鼠血吸虫性结肠炎中的表达及其意义。方法:将40只BALB/c雄性小鼠随机分成正常对照组和感染组。小鼠腹部贴片感染约40条日本血吸虫尾蚴建立血吸虫性结肠炎模型。8周后处死小鼠,行HE染色,伊文思蓝法检测肠道血管内皮细胞通透性,计数腹腔灌洗液中的白细胞,qPCR法检测结肠组织中caveolin-1、occludin、claudin-1、eNOS mRNA表达,蛋白质印迹法和免疫组化检测caveolin-1和occludin蛋白表达。结果:感染组结肠黏膜下层可见大量虫卵肉芽肿,并伴有肠壁广泛的炎症细胞浸润。与正常对照组相比,感染组腹腔灌洗液中伊文思蓝含量和白细胞计数均显著升高(P<0.05),caveolin-1、occludin、claudin-1 mRNA表达显著降低(P<0.01),caveolin-1、occludin蛋白表达和阳性率均显著降低(P<0.05)。结论:Caveolin-1、occludin和claudin-1表达下调可能通过影响肠道血管内皮细胞的通透性,诱发白细胞聚集,从而参与血吸虫性结肠炎的发病。

Background：Intestinal schistosomiasis is a kind of intravascular parasitic diseases,and chronic inflammation of colon is one of the basic pathological changes of the sickness.However,the mechanism of caveolin-1 and tight junction proteins in the pathogenesis of intestinal schistosomiasis is still unclear.Aims：To study the expressions and significances of caveolin-1 and tight junction protein occludin,claudin-1 in schistosomiasis colitis in mice.Methods：Forty BALB/c male mice were randomly divided into control group and infection group.Schistosomiasis colitis model was established by placing40 Schistosoma Japonicum cercarie on the abdomen.Mice were sacrificed after 8 weeks.HE staining was performed.The permeability of intestinal vascular endothelium was detected by Evans blue method.The leukocyte counts in peritoneal lavage fluid were measured.qP CR was used to determine the mRNA expressions of caveolin-1,occludin,claudin-1 and eN OS in colon tissue.Western blotting and immunohistochemistry were used to detect the protein expressions of caveolin-1and occludin.Results：Large number of egg granuloma was observed in colon submucosa and accompanied by extensive inflammatory cells infiltration in infection group.Compared with control group,content of Evans blue and leukocyte counts in peritoneal lavage fluid were significantly increased（P〈0.05）;mRNA expressions of caveolin-1,occludin,claudin-1were significantly decreased（P〈0.01）;protein expressions and positivity rates of caveolin-1 and occludin were significantly decreased in infection group（P〈0.05）.Conclusions：Down-regulation of expressions of caveolin-1,occludin and claudin-1 can induce leukocyte accumulation via increasing the permeability of intestinal vascular endothelial cells,thereby involving in the development of schistosomiasis colitis.