ENHANCEMENT OF RETICULOENDOTHELIAL FUNCTION IN THE TREATMENT OF ACUTE HEPATIC FAILURE

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，以及增强其抑制的RES功能是否有益于AHF的治疗。本实验用氨基半乳糖诱导大鼠急性心力衰竭，并用脂肪乳法测定其RES吞噬活性。以动脉血酮体比(AKBR)检测肝细胞线粒体功能，并检测血中补体C3、纤维连接蛋白等调理蛋白水平。AHF大鼠的RES吞噬活性和AKBR显著降低，血中调理蛋白水平明显降低。这些大鼠被给予三磷酸腺苷-镁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。经上述治疗后，AHF大鼠的RES吞噬活性和AKBR均有不同程度的提高，调理蛋白的耗竭也有所改善。最重要的是，给予ATP-MG和/或OK-432治疗的大鼠，与没有增强RES的AHR大鼠相比，存活率有所提高。考虑到实验研究的结果，AHF患者在常规人工肝支持治疗的基础上，给予大剂量新鲜冰冻血浆以改善调理蛋白水平，并给予OK-432以增强RES功能。SHF患者的AKBR和Opsonic蛋白水平均有改善，且存活率较高。提示Res吞噬活性降低可能是AHF发病的关键因素之一，Res吞噬活性增强可能有助于AHF的治疗。

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.