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

为了确定肠道寄生虫吸收不良的原因，研究了感染巴西尼波圆线虫的大鼠肠道吸收细胞的病理改变。线虫感染引起肠上皮细胞病变，细胞凋亡增强，绒毛萎缩发生。对胸腺肥大/肥大和肥大细胞缺陷大鼠的研究表明，绒毛萎缩的进展依赖于T细胞，而不依赖于肥大细胞的活化，其发生与上皮和固有粘膜颗粒酶b阳性细胞数量的增加有关。T细胞非依赖性细胞病变也被发现，这可能与TNF上调有关。此外，体外研究表明，巴西隐杆线虫在肠上皮细胞系IEC-6中产生并分泌一种可诱导Fas上调和凋亡的因子。巴西芽孢杆菌感染诱导低血糖和低白蛋白血症，这些改变与吸收细胞中葡萄糖转运体SGLT1和GLUT5、肽转运体PepT1和氨基酸转运体LAT2的表达降低有关。这些结果表明，线虫感染诱导肠道吸收细胞T细胞依赖性和非依赖性凋亡和细胞病变改变，并降低转运蛋白分子的表达，从而使营养物质吸收恶化。

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.