Molecular mechanisms of glucose transporter alterations and apoptosis progression in intestinal parasitoses

为了确定肠道寄生虫病吸收不良的原因，在肠道吸收细胞的病理变化进行了检查，在感染线虫巴西日本圆线虫大鼠。线虫感染引起的细胞病变和肠上皮细胞的细胞凋亡，以及绒毛萎缩的发展。在无胸腺rnu/rnu和肥大细胞缺陷的Ws/Ws大鼠的研究表明，绒毛萎缩的进展是依赖于T细胞，但不是肥大细胞的活化，其发生与颗粒酶B阳性细胞的上皮和固有粘膜中的数量增加。还发现了T细胞非依赖性细胞病变，这可能与TNF上调有关。此外，体外研究表明，N。巴西蠕虫产生和分泌的因子，可以诱导上调Fas和肠上皮细胞系IEC-6的凋亡。N.巴西感染引起低血糖和低白蛋白血症，这些变化与吸收细胞中葡萄糖转运蛋白SGLT 1和GLUT 5、肽转运蛋白PepT 1和氨基酸转运蛋白LAT 2的表达降低有关。这些结果表明，线虫感染诱导T细胞依赖性和非依赖性的细胞凋亡和细胞病变的肠吸收细胞连同转运蛋白分子的表达减少，这可能会恶化营养吸收。

To determine the cause of malabsorption in intestinal parasitoses, pathological alterations in the intestinal absorptive cells were examined in rats infected with the nematode Nippostrongylus brasiliensis. Nematode infection induced cytopathic alterations and enhanced apoptosis in the intestinal epithelial cells together with the development of villus atrophy. Studies in athymic rnu/rnu and mast cell-deficient Ws/Ws rats revealed that progression of the villus atrophy was dependent on T cells, but not on mast-cell activation, and its occurrence was associated with the increase in number of granzyme B-positive cells in the epithelium and the propria mucosa. T cell-independent cytopathic change was also found, that was possibly associated with TNF up-regulation. In addition, in-vitro studies clarified that N. brasiliensis worms produced and secreted a factor that could induce up-regulation of Fas and apoptosis in the intestinal epithelial cell line IEC-6. N. brasiliensis infection induced hypoglycemia and hypoalbuminemia, and these alterations were associated with decreased expression of glucose transporters SGLT1 and GLUT5,the peptide transporter PepT1,and the amino acid transporter LAT2 in the absorptive cells. These results indicated that nematode infection induces T cell-dependent and -independent apoptosis and cytopathic alterations in the intestinal absorptive cells together with decreased expression of transporter molecules, that could deteriorate nutrient absorption.