The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine
The interaction between high ammonia diet and bile duct ligation in developing rats: assessment by spatial memory and asymmetric dimethylarginine
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DOI：
10.1016/j.ijdevneu.2009.11.006
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发表时间：
2010-04-01
影响因子：
1.8
通讯作者：
Tain, You-Lin
中科院分区：
文献类型：
--
作者：
Huang, Li-Tung;Chen, Chih-Cheng;Tain, You-Lin
发育期大鼠胆管结扎(BDL)可导致胆汁淤积、肝功能和认知功能损害。因为一氧化氮(NO)和氨都与肝性脑病(HE)有关，我们假设内源性一氧化氮合酶抑制剂不对称二甲基精氨酸(ADMA)和氨影响BDL幼鼠的认知。将17日龄雄性SD大鼠分为4组：开腹组(SC组)、开腹+30%醋酸铵饲料组(SC+HA组)、BDL组(BDL组)、BDL+高氨饲料组(BDL+HA组)。用Morris水迷宫测试大鼠的空间记忆。采集血浆进行生化和ADMA分析。收集肝脏和大脑皮质，测定精氨酸甲基转移酶-1(PRMT1)的蛋白含量。ADMA合成酶)和二甲基精氨酸二甲氨基水解酶(DDAH，ADMA代谢酶)。BDL组血浆直接胆红素/总胆红素、天冬氨酸氨基转移酶、丙氨酸氨基转移酶、ADMA、肝组织p22(Phox)水平显著高于SC组，空间作业能力明显低于SC组。高氨饮食增加血氨和ADMA浓度，并在存在BDL诱导的胆汁淤积时加重空间缺陷。我们认为，血浆ADMA在BDL所致的空间缺陷中起一定作用。高氨加重了胆汁淤积症幼鼠的空间缺陷。(C)2009年综合业务数字网。爱思唯尔有限公司出版。保留所有权利。
Bile duct ligation (BDL) in developing rats causes cholestasis, impaired liver function and cognition. Because both nitric oxide (NO) and ammonia are implicated in hepatic encephalopathy (HE), we hypothesized that asymmetric dimethylarginine (ADMA), an endogenous NO synthase inhibitor, and ammonia affect cognition in young rats with BDL. Four groups of young male Sprague-Dawley rats ages 17 days were used: rat underwent laparotomy (SC group), rat underwent laparotomy plus a 30% ammonium acetate diet (SC + HA group), rat underwent BDL (BDL group), rats underwent BDL plus high ammonia diet (BDL + HA group). Spatial memory was assessed by Morris water maze task. Plasma was collected for biochemical and ADMA analyses. Liver and brain cortex were collected for determination of protein arginine methyltransferase-1 (PRMT1. ADMA-synthesizing enzyme) and dimethylarginine dimethylaminohydrolase (DDAH, ADMA-metabolizing enzyme). We found BDL group had significantly higher plasma direct/total bilirubin, aspartate aminotransferase, alanine aminotransferase, ADMA, liver p22(phox), and worse spatial performance as compared with SC group. High ammonia diet increased plasma ammonia and ADMA concentration, and aggravated spatial deficit in the presence of BDL-induced cholestasis. We conclude plasma ADMA plays a role in BDL-induced spatial deficit. High ammonia aggravated the spatial deficits encountered in cholestatic young rats. (C) 2009 ISDN. Published by Elsevier Ltd. All rights reserved.