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为探讨引入二硫吡啶硫酮(PDP)基团后,蓖麻毒素(RT)毒性降低和免疫增强的机理,作者将用异型双功能交联剂3-(2-吡啶二硫基)丙酸琥珀酰亚胺酯(SPDP)修饰的蓖麻毒素(RT-PDP)与其未修饰的蓖麻毒素注入小鼠腹腔内,然后取小鼠的心、肝、脾、肺、肾等主要脏器进行了免疫组化定位和计算机辅助图像分析。结果发现,二者都主要集中在网状内皮组织系统如脾、肝中,但RT-PDP含量明显少于RT(P<0.05).从切片上可见RT对组织损伤严重,出现细胞空泡样变性,组织出血,萎缩,坏死等现象;而RT-PDP在组织中未引起上述现象,且对Kupffer细胞有活化趋势。提示RT-PDP对主要脏器组织亲和力和毒性明显降低,且有可能产生一种活化吞噬细胞的新功能,从而为蓖麻毒素的开发应用提供一种新的思路。
In order to explore the mechanism of toxicity and immune enhancement of ricin (RT) after introduction of a disulfiridine thione (PDP) group, the authors used the heterobifunctional cross-linker 3- (2-pyridyldithio) propionic acid Succinimide ester (SPDP) -modified ricin (RT-PDP) and its unmodified ricin were injected into the peritoneal cavity of mice and then taken from the major organs such as heart, liver, spleen, lung and kidney in mice Immunohistochemical localization and computer-assisted image analysis. The results showed that both were mainly in the reticuloendothelial system such as spleen and liver, but the content of RT-PDP was significantly less than RT (P <0.05). From the slices, it can be seen that RT has serious damage to the tissue, such as vacuolar degeneration, tissue hemorrhage, atrophy and necrosis. However, RT-PDP did not cause the above phenomenon in the tissue and activated Kupffer cells. It is suggested that the affinity and toxicity of RT-PDP to the major organs are significantly reduced, and it is possible to produce a new function of activating phagocytes, thus providing a new idea for the development and application of ricin.