INTRASPLENIC HEPATOCELLULAR TRANSPLANTATION CORRECTS HEPATIC-ENCEPHALOPATHY IN PORTACAVAL-SHUNTED RATS

INTRASPLENIC HEPATOCELLULAR TRANSPLANTATION CORRECTS HEPATIC-ENCEPHALOPATHY IN PORTACAVAL-SHUNTED RATS
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DOI:
10.1002/hep.1840150104
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发表时间:
1992-01-01
期刊:
影响因子:
13.5
通讯作者:
PANIS, Y
PANIS, Y
中科院分区:
医学1区
文献类型:
--
作者:
RIBEIRO, J;NORDLINGER, B;PANIS, Y

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本工作的目的是在大鼠门腔静脉端侧分流诱发的慢性肝衰竭实验模型中评估脾内肝细胞移植对肝性脑病的影响。 将近交系雄性 Wistar Furth 大鼠分为三组:接受门腔静脉分流术的大鼠(n = 10)、接受门腔静脉分流术并从同系大鼠肝脏分离的 10(7)个肝细胞进行脾内肝细胞移植的大鼠(n = 10)和假手术大鼠(n = 10)。 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化开放场地箱中研究了大鼠个体的自发活动和鼻子戳探。 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)。 测量氨基酸、氨和总胆酸的血浆水平。 门静脉分流术大鼠表现出自发活动和鼻戳探查评分降低。 脾内肝细胞移植在 2 个月后显着增加了自发活动,并在 3 周后改善了鼻戳探查。 3个月时,门静脉分流/脾内肝细胞移植大鼠的自发活动和鼻戳探查与假手术大鼠没有显着差异。 门静脉分流术后血浆氨水平升高未得到纠正。 血浆中氨基酸失衡和胆汁酸浓度通过脾内肝细胞移植得到部分纠正。 这些数据表明,脾内肝细胞移植可以纠正慢性肝衰竭实验模型中肝性脑病的神经症状,并表明脾内肝细胞移植可能对慢性肝衰竭具有治疗意义。
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.