Experimental studies on mechanisms and treatments of brain edema in acute hepatic failure

以肝性脑病血脑屏障（BBB）功能障碍为研究对象，探讨急性肝衰竭（AHF）模型脑水肿的发生机制及治疗方法。通过腹腔注射d -半乳糖胺盐酸盐（GalN）和脂多糖建立实验性AHF大鼠模型。1)随着肝性脑病病情的恶化，脑含水量逐渐升高。此外，根据Oldendorf法，AHF大鼠模型显示菊粉通过血脑屏障的通透性逐渐增加（约5200道尔顿）。2)在GalN和LPS处理后8、16、24小时静脉给予甘露醇，AHF大鼠模型脑水含量显著降低。然而，甘露醇的这种作用随着肝性脑病的进展而减弱，这是由于血脑屏障通透性和甘露醇脑浓度的升高。因此，甘露醇治疗脑水肿应在肝性脑病早期开始。3)前列腺素I_2（PGI_2）衍生物与前列腺素E_1（PG E_1）或生理盐水注射AHF大鼠模型相比，显著降低脑含水量和菊粉通过血脑屏障的通透性。PGI_2衍生物可以抑制血脑屏障的通透性，并保持血脑屏障的完整性，对AHF脑水肿有一定的影响。甘露醇联合PGI_2衍生物与单用甘露醇或PGI_2衍生物相比，能显著抑制AHF大鼠模型脑水肿的进展。PGI_2衍生物抑制甘露醇通过血脑屏障的渗透性，降低甘露醇在脑内的浓度。因此，甘露醇加PGI_2衍生物治疗AHF脑水肿更为有效。

Experimental studies were conducted to investigate the mechanisms and treatments of brain edema in acute hepatic failure(AHF) model, with special reference to functional disorders of the blood-brain barrier(BBB) in hepatic encephalopathy. The experimental AHF rat model was produced by intraperitoneal administration of D-galactosamine hydrochloride(GalN) and lipopolysaccaride.1) Brain water contents were gradually increased according to deterioration of hepatic encephalopathy. In addition, AHF rat model showed gradual increase of permeability of inulin(approximately 5,200 daltons) through the BBB by Oldendorf's method.2) Brain water contents in AHF rat model significantly decreased, when mannitol was administered intravenously at 8, 16, and 24 hours after treatment of GalN and LPS.However, this effect of mannitol weakened in parallel with progression of hepatic encephalopathy, due to the elevation of permeability through the BBB and brain concentration of mannitol. Therefore, mannitol treatment for brain edema should be started in earlier stage of hepatic encephalopathy.3) Prostaglandin I_2(PGI_2) derivative administration significantly decreased brain water contents and permeability of inulin through the BBB, when compared with prostaglandin E_1(PG E_1) or saline injected AHF rat model. PGI_2 derivative was considered to show the effect for brain edema in AHF, due to inhibition of BBB permeability and preservation of its integrity.Mannitol treatment together with PGI_2 derivative significantly inhibited the progression of brain edema in AHF rat model, when compared with mannitol or PGI_2 derivative alone, respectively. PGI_2 derivative inhibited the permeability of mannitol through BBB, and decreased mannitol concentration in brain. Therefore, administration of mannitol with PGI_2 derivative was considered to be more effective to brain edema in AHF.