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大鼠阻塞性黄疸:胆道减压后空间记忆缺陷的原因及恢复情况

Obstructive jaundice in rats: cause of spatial memory deficits with recovery after biliary decompression.

作者信息

Huang Li-Tung, Hsieh Chih-Sung, Chou Ming-Huei, Chuang Jiin-Haur, Liou Chia-Wei, Tiao Mao-Meng, Lai Ming-Chi

机构信息

Department of Pediatrics, Chang Gung Memorial Hospital, 123 Ta-Pei Road, Niao-Sung Hsiang, Kaohsiung, Taiwan.

出版信息

World J Surg. 2004 Mar;28(3):283-7. doi: 10.1007/s00268-003-7209-z. Epub 2004 Feb 17.

Abstract

Children with end-stage liver disease have been found to have cognitive deficits. The aim of this study was to examine whether cholestatic jaundice causes spatial deficits in rats and if these cognitive deficits are reversed by biliary drainage. Rats were randomly divided into three groups. In the first group, the bile duct was ligated for 3 weeks (BDL group); in the second group, the proximal bile duct was ligated with a Broviac CV catheter for 2 weeks followed by a tube bilioduodenostomy (TBD group); in the third group, a sham operation was performed (SHAM group). All the surviving rats were assessed for spatial learning and memory (a major cognitive function in rats) by the Morris water maze task about 3 weeks after the first operation. Blood was aspirated by cardiocentesis and assayed for total bilirubin, albumin, ammonia, and hemoglobin levels on the day following the water maze task. During the four consecutive acquisition trial days of the Morris water maze, jaundiced rats (BDL group) had a significant longer latency to escape than the SHAM group ( p < 0.05). Rats that underwent biliary decompression for 1 week (TBD group) showed improved status of the spatial deficit, as they required less time to reach the escape platform, approaching the performance of the SHAM group. The BDL group had a significantly higher serum ammonia level, higher bilirubin level, and lower hemoglobin level than the other two groups. After biliary decompression for 1 week, the serum albumin concentration in the TBD group still did not return to the level of the SHAM group. The results of this study suggest that long-term cholestasis results in spatial memory deficits in rats that correlate with anemia and hyperbilirubinemia encephalopathy. Early biliary decompression of obstructive jaundice improves spatial memory deficits, possibly related to the recovery of the serum ammonia and hemoglobin levels.

摘要

已发现终末期肝病患儿存在认知缺陷。本研究的目的是检验胆汁淤积性黄疸是否会导致大鼠出现空间缺陷,以及这些认知缺陷是否可通过胆汁引流得到逆转。大鼠被随机分为三组。第一组,胆管结扎3周(胆管结扎组);第二组,近端胆管用Broviac CV导管结扎2周,随后行胆管十二指肠吻合术(胆管十二指肠吻合组);第三组,进行假手术(假手术组)。在首次手术后约3周,通过莫里斯水迷宫任务对所有存活大鼠的空间学习和记忆(大鼠的一项主要认知功能)进行评估。在水迷宫任务后的第二天,通过心脏穿刺采血,检测总胆红素、白蛋白、氨和血红蛋白水平。在莫里斯水迷宫连续四天的获取试验中,黄疸大鼠(胆管结扎组)的逃避潜伏期明显长于假手术组(p<0.05)。接受胆汁减压1周的大鼠(胆管十二指肠吻合组)显示空间缺陷状况有所改善,因为它们到达逃避平台所需时间减少,接近假手术组的表现。胆管结扎组的血清氨水平显著高于其他两组,胆红素水平更高,血红蛋白水平更低。胆汁减压1周后,胆管十二指肠吻合组的血清白蛋白浓度仍未恢复到假手术组的水平。本研究结果表明,长期胆汁淤积会导致大鼠出现空间记忆缺陷,这与贫血和高胆红素血症性脑病相关。早期对梗阻性黄疸进行胆汁减压可改善空间记忆缺陷,可能与血清氨和血红蛋白水平的恢复有关。

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