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

本实验旨在探讨急性肝功能衰竭（AHF）模型脑水肿的发生机制和治疗方法，特别是肝性脑病时血脑屏障（BBB）功能障碍。采用D-氨基半乳糖盐酸盐（GalN）和脂多糖腹腔注射制备实验性AHF大鼠模型。此外，AHF大鼠模型显示菊糖渗透性逐渐增加（2）在GalN和LPS治疗后8、16和24 h静脉注射甘露醇可显著降低AHF大鼠脑含水量，但甘露醇的这种作用随着肝性脑病的进展而减弱，这是由于通过BBB的渗透性和甘露醇的脑浓度升高。3）与前列腺素E_1（PGE_1）或生理盐水注射的AHF大鼠模型相比，前列腺素I_2（PGI_2）衍生物可显著降低AHF大鼠脑组织含水量和菊糖通过血脑屏障的通透性。PGI_2衍生物可抑制血脑屏障通透性，保护血脑屏障的完整性，对AHF大鼠脑水肿有一定的治疗作用，甘露醇与PGI_2衍生物合用，与甘露醇或PGI_2衍生物单用相比，可明显抑制AHF大鼠脑水肿的进展。PGI_2衍生物可抑制甘露醇通过血脑屏障的通透性，降低脑内甘露醇浓度。因此，甘露醇与PGI_2衍生物联合应用对AHF脑水肿的治疗更为有效。

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.