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ENHANCEMENT OF RETICULOENDOTHELIAL FUNCTION IN THE TREATMENT OF ACUTE HEPATIC FAILURE

增强网状内皮功能治疗急性肝衰竭

基本信息

批准号：
61570734
负责人：
HIRASAWA Hiroyuki
金额：
$ 1.34万
依托单位：
Chiba University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1986
资助国家：
日本
起止时间：
1986 至 1988
项目状态：
已结题

项目摘要

The present study was undertaken to investigate whether the reticuloendothelial (RES)phagocytic activity would be depressed in acute hepatic failure (AHF) and whether the enhancement of the depressed RES function would be beneficial in the treatment of AHF. In the experimental study AHF was induced with galactosamine in rats, and the RES phagocytic activity was measured with lipid emulsion method. Furthermore hepatic cellular mitochondrial function was investigated with arterial ketone body ratio (AKBR) and blood level of opsonic proteins such as C3 and fibronection was also investigated. The AHF rats showed the significant depressions in the RES phagocytic activity and AKBR, and depleted blood level of opsonic proteins. These rats were administered ATP-Mg to improve the impaired mitochondrial function and also given the non-specific immunomodulator, OK-432. With these treatments, the AHF rats showed the improvement in the RES phagocytic activity and AKBR, and the repletion of opsonic proteins. And most importantly the rats treated with ATP-Mg and/or OK-432 showed the improved survival rate compared to the AHR rats'without RES enhancement. Taking those results of the experimental study into consideration, the patients with AHF was given massive dose of fresh frozen plasma in order to improve the opsonic protein levels and OK-432 to enhance the RES function besides the conventional artificial liver support therapy with plasma exchange and hemoadsorption. The SHF patients showed the improvement in AKBR and opsonic protein levels and showed the better survival with these treatments. These results suggest that the depression in RES phabocytic activity can play one of the key roles in the pathogenesis of AHF and that the enhancement of the RES phagocytic activity could be beneficial in the treatment of the AHF.

本研究旨在探讨急性肝功能衰竭（AHF）时网状内皮细胞（RES）吞噬功能是否受到抑制，以及增强受抑制的RES功能是否有利于AHF的治疗。本实验采用氨基半乳糖诱发大鼠急性肝衰竭，用脂肪乳剂法测定RES吞噬活性。此外，还用动脉酮体比率（AKBR）研究了肝细胞线粒体功能，并研究了血液调理蛋白如C3和纤维连接蛋白的水平。AHF大鼠RES吞噬活性和AKBR显著降低，血液调理蛋白水平降低。给予这些大鼠ATP-Mg以改善受损的线粒体功能，并给予非特异性免疫调节剂OK-432。通过这些治疗，AHF大鼠表现出RES吞噬活性和AKBR的改善，以及调理蛋白的补充。最重要的是，与没有RES增强的AHR大鼠相比，用ATP-Mg和/或OK-432治疗的大鼠显示出改善的存活率。根据上述实验研究结果，在常规人工肝支持治疗的基础上，采用血浆置换、血液吸附等方法，给予大剂量新鲜冰冻血浆，以提高调理素水平，并给予OK-432，以增强RES功能。SHF患者显示AKBR和调理素蛋白水平的改善，并显示这些治疗的生存率更高。提示RES吞噬活性的降低在AHF发病机制中起重要作用，增强RES吞噬活性可能有助于AHF的治疗。