The Role of Selections in The Formation of Glomerular Thrombi

由于肾小球血栓发生于多种肾小球疾病，是进行性肾损伤的重要病理参数，本项目旨在探讨选择和选择素配体在肾小球血栓形成中的作用。本研究研究了p -选择素在肾小球血栓形成中的作用以及合成选择素阻滞剂的治疗效果。第一部分实验采用肾下剂量LPS加肾毒性球蛋白致血栓性微血管病变大鼠模型，实验结果如下：(1)微血栓的形成完全依赖于白细胞在肾小球中的浸润，环磷酰胺耗尽循环白细胞完全阻断了血栓的形成。(2)检测p -选择素在肾小球中的选择性表达。抗p -选择素抗体在10分钟显著阻断血小板在肾小球内的聚集，在6小时显著阻断白细胞的浸润和血栓的形成。(3) p选择素受体阻断合成硫脂衍生物（SKK-60037）对肾小球血栓形成的保护作用与抗p选择抗体相似。这些结果表明p -选择素显著参与了微血栓的形成过程，合成硫脂衍生物（SKK-60037）可能在进行性肾损伤的临床应用中具有潜力。第二部分，检测n -乙酰氨基葡萄糖-6-o-硫代转移酶mRNA在胎儿肾脏表位的表达。结果如下：虽然在上皮细胞中检测到n -乙酰氨基-6-o-磺基转移酶mRNA的显著表达，但在胎儿肾脏中未检测到6-磺基LewisX或6-磺基LewisX等表位。这些结果表明，聚焦转移酶和/或唾液转移酶的额外表达可能是肾脏中选择素配体表达所必需的。少

The aim of this project was to investigate the role of selections and selectin ligands in the formation of glomerular thrombi, since glomerular thrombi occurs various glomerular diseases and is an important pathological parameter for the progressive renal injuries. In the present study, the role of P-selectin in the formation of glomerular thrombi and the therapeutical effects of synthetic selectin blocker were studied. In the first part of experiment using a rat model of thrombotic microangiopathy induced by injection of subnephritic dose of LPS followed by nephrotoxic globulin,the following results were obtained. (1) The formation of microthrombi completely depended on the leukocyte infiltration in glomeruli, since depletion of circulating leukocytes by cyclophosphamide completely blocked the formation on thrombi. (2) Selective expression of P-selectin in glomeruli was detected. Anti P-selectin antibody prominently blocked platelets aggregation in glomeruli at 10 minutes, and signifi … More cantly blocked the infiltration of leukocytes and the formation thrombi at 6 hrs. (3) P-selectin receptor-blocking synthetic sulfatide derivative (SKK-60037) showed similar protective effects on the formation glomerular thrombi as those of anti P-selection antibody. These results indicate that P-selectin was significantly involved in the process of the formation on microthrombi, and synthetic sulfatide derivative (SKK-60037) may have potential for clinical application of progressive renal injuries. In the second part, the expression of N-acetylglucosamine-6-o-sulfotransferase mRNA was detected in the epitopes induced by this enzyme in fetal kidneys was studied. The results were as follow ; although prominent expression of N-acetylglucosamine-6-o-sulfotransferase mRNA was detected in the epithelial cells, the epitopes such as 6-sulfo LewisX or 6-sulfo sialyl Lewis X were not detected in fetal kidneys. These results indicate that the additional expression of fucosyltransferases and/or sialyltransferases might be requisite for expression of selectin ligands in the kidney. Less