Ribeiro J, Nordlinger B, Ballet F, Cynober L, Coudray-Lucas C, Baudrimont M, Legendre C, Delelo R, Panis Y
INSERM U.181, Hôpital Saint-Antoine, Paris, France.
Hepatology. 1992 Jan;15(1):12-8. doi: 10.1002/hep.1840150104.
The aim of this work was to evaluate the effect of intrasplenic hepatocellular transplantation on hepatic encephalopathy in an experimental model of chronic liver failure induced by end-to-side portacaval shunt in the rat. Inbred male Wistar Furth rats were divided into three groups: rats subjected to portacaval shunt (n = 10), rats subjected to portacaval shunt and intrasplenic hepatocellular transplantation of 10(7) hepatocytes isolated from livers of syngeneic rats (n = 10) and sham-operated rats (n = 10). Behavior tests were performed in a blind fashion at 3 wk, at 2 mo and at 3 mo after surgery. Spontaneous activity and nose-poke exploration by individual rats were studied in automated open field boxes equipped with infrared cells. Each cell beam interruption was automatically recorded on a microcomputer and transformed into a score index (counts/hour). Plasma levels of amino acids, ammonia and total biliary acids were measured. Portacaval shunt rats showed reduced spontaneous activity and nose-poke exploration scores. Intrasplenic hepatocellular transplantation significantly increased spontaneous activity after 2 mo and improved nose-poke exploration after 3 wk. At 3 mo, spontaneous activity and nose-poke exploration in portacaval shunt/intrasplenic hepatocellular transplantation rats were not significantly different from those of sham rats. Increases in plasma ammonia levels after portacaval shunt were not corrected. Amino acid imbalance and bile acid concentration in plasma were partially corrected by intrasplenic hepatocellular transplantation. These data show that intrasplenic hepatocellular transplantation can correct the neurological symptoms of hepatic encephalopathy in an experimental model of chronic liver failure and suggest that intrasplenic hepatocellular transplantation might be of therapeutic interest in chronic liver failure.
本研究旨在评估在大鼠端侧门腔分流诱导的慢性肝衰竭实验模型中，脾内肝细胞移植对肝性脑病的影响。近交系雄性Wistar Furth大鼠被分为三组：接受门腔分流的大鼠（n = 10）、接受门腔分流并移植从同基因大鼠肝脏分离的10(7)个肝细胞的大鼠（n = 10）和假手术大鼠（n = 10）。在术后3周、2个月和3个月以盲法进行行为测试。在配备红外细胞的自动旷场箱中研究个体大鼠的自发活动和探鼻探索行为。每次细胞束中断都会自动记录在微型计算机上，并转化为评分指数（计数/小时）。测量血浆氨基酸、氨和总胆汁酸水平。门腔分流大鼠的自发活动和探鼻探索评分降低。脾内肝细胞移植在2个月后显著增加了自发活动，并在3周后改善了探鼻探索行为。在3个月时，门腔分流/脾内肝细胞移植大鼠的自发活动和探鼻探索与假手术大鼠无显著差异。门腔分流后血浆氨水平的升高未得到纠正。脾内肝细胞移植部分纠正了血浆中的氨基酸失衡和胆汁酸浓度。这些数据表明，在慢性肝衰竭实验模型中，脾内肝细胞移植可以纠正肝性脑病的神经症状，并提示脾内肝细胞移植可能对慢性肝衰竭具有治疗意义。
