Ochiai T, Naito K, Murakami O, Ohno K, Sekita K, Furuya T, Kurokawa Y, Matsumoto K, Saito Y, Hachisuka A
Eisei Shikenjo Hokoku. 1993(111):91-9.
Immunotoxicological effects of cyclosporin A (CsA) were studied by enhanced histopathological and functional tests in rats. Male F344 rats were orally administered with CsA in doses of 0, 2.5, 10, and 40 mg/kg/day for 28 successive days. Hematological examination revealed that the CsA treatment brought about a marked dose-dependent decrease in the number of WBCs, which was attributed to a decrease in the number of lymphocytes. In the femoral bone marrow, a significant reduction in the number of nucleated cells was observed, which was attributed to a decrease in the number of lymphocytes and erythroblasts. Histopathologically, diminution of thymic medullas, appearance of tangible body macrophages in thymic cortices, and calcification and basophilic changes in kidneys were observed in the middle and high dose groups. Immunohistological examination with anti-rat T lymphocyte antibody showed a decrease in the number of T cells at the periarterial lymphatic sheaths in the spleens. As for the functional tests, CsA treatment remarkably reduced the PFC number even in the low dose group. The Con A response of spleen cells was decreased in the middle and high dose groups. The STM response was reduced only in the high dose group. The NK activity was little affected. Thus, in the CsA-treated F344 rats, the enhanced histopathological and some functional tests which were proposed by ICICIS, were found to be useful to detect damages to the immune system.
通过增强组织病理学和功能测试，在大鼠中研究了环孢素A（CsA）的免疫毒理学效应。雄性F344大鼠连续28天口服给予剂量为0、2.5、10和40 mg/kg/天的CsA。血液学检查显示，CsA治疗导致白细胞数量显著呈剂量依赖性减少，这归因于淋巴细胞数量的减少。在股骨骨髓中，观察到有核细胞数量显著减少，这归因于淋巴细胞和红细胞数量的减少。组织病理学上，中、高剂量组观察到胸腺髓质减少、胸腺皮质出现可触知体巨噬细胞以及肾脏钙化和嗜碱性改变。用抗大鼠T淋巴细胞抗体进行免疫组织学检查显示，脾脏动脉周围淋巴鞘中的T细胞数量减少。至于功能测试，即使在低剂量组，CsA治疗也显著降低了PFC数量。中、高剂量组脾脏细胞的Con A反应降低。STM反应仅在高剂量组降低。NK活性几乎未受影响。因此，在经CsA处理的F344大鼠中，发现ICICIS提出的增强组织病理学和一些功能测试对于检测免疫系统损伤是有用的。
