Pediatrics Department, Chang-Gung Memorial Hospital-Kaohsiung Medical Center, Chang-Gung University College of Medicine, Niao Song, Kaohsiung, Taiwan.
Dig Dis Sci. 2010 Oct;55(10):2831-7. doi: 10.1007/s10620-009-1120-x. Epub 2010 Jan 26.
Cognitive deficiency noted post-liver transplantation might be a result of consequential metabolic derangement before liver transplantation. Long-chain polyunsaturated fatty acids, especially arachidonic acid (AA) and docosahexaenoic acid (DHA), affect the development of the central nervous system and its absorption is influenced by obstructive jaundice.
To investigate the possible relationship between the brain content of AA and DHA with the severity of obstructive jaundice using a bile duct ligation rat model.
Sprague-Dawley rats were divided into three groups: Sham (n = 5): rats received sham operation on P17 (17 days after delivery) and were sacrificed on P31; BDL2w (n = 5): rats received bile duct ligation and were sacrificed on P31; BDL4w (n = 7): rats received bile duct ligation and were sacrificed on P45. Liver function test, histopathology, and fatty acid composition of the brain tissues were analyzed.
The Sham group had significantly lowered total/direct bilirubin level (0.6 + 0.1/0.3 + 0.1 mg/dl) as compared to the BDL2w group (3.8 + 1.5/1.6 + 1.0 mg/dl) and the BDL4w group (4.3 + 0.6/3.3 + 0.5 mg/dl) (P = 0.04 and 0.008, respectively). Liver fibrosis and inflammatory changes of hepatocytes increased from the Sham group, the BDL2w group, to the BDL4w group. The Sham group had significantly higher AA and DHA content. The brain content of AA and DHA correlated negatively to the duration of bile duct ligation, the total/direct bilirubin level, and the degree of liver fibrosis.
Our results demonstrated that reduced AA and DHA content in the brain of rats which received bile duct ligation is closely related to both the severity of liver fibrosis and the impairment of liver function.
肝移植后出现的认知功能障碍可能是肝移植前继发代谢紊乱的结果。长链多不饱和脂肪酸,尤其是花生四烯酸(AA)和二十二碳六烯酸(DHA),影响中枢神经系统的发育,其吸收受梗阻性黄疸的影响。
使用胆管结扎大鼠模型,研究大脑中 AA 和 DHA 含量与梗阻性黄疸严重程度之间的可能关系。
将 Sprague-Dawley 大鼠分为三组:假手术组(n = 5):大鼠于 P17 行假手术,于 P31 处死;胆管结扎 2 周组(n = 5):大鼠行胆管结扎,于 P31 处死;胆管结扎 4 周组(n = 7):大鼠行胆管结扎,于 P45 处死。分析肝功能试验、组织病理学和脑组织脂肪酸组成。
与胆管结扎 2 周组(3.8 + 1.5/1.6 + 1.0 mg/dl)和胆管结扎 4 周组(4.3 + 0.6/3.3 + 0.5 mg/dl)相比,假手术组的总胆红素/直接胆红素水平(0.6 + 0.1/0.3 + 0.1 mg/dl)明显降低(P = 0.04 和 0.008)。从假手术组到胆管结扎 2 周组,再到胆管结扎 4 周组,肝纤维化和肝细胞炎症变化逐渐加重。假手术组的 AA 和 DHA 含量明显较高。大脑中 AA 和 DHA 的含量与胆管结扎时间、总胆红素/直接胆红素水平和肝纤维化程度呈负相关。
我们的结果表明,接受胆管结扎的大鼠大脑中 AA 和 DHA 含量减少与肝纤维化严重程度和肝功能损害密切相关。