乌司他丁后处理对肝切除老年大鼠学习记忆功能的影响及机制研究

目的观察乌司他丁（UTI）后处理对肝部分切除术（PH）老年大鼠学习记忆能力的影响并探讨其作用机制。 方法选择健康雄性无特定病原体SPF级C57BL/6J大鼠36只,18月龄,体质量27~36 g。按照随机数字表法将大鼠分为3组：对照组（C组）、肝部分切除术组（PH组）和UTI后处理组（UTI组），每组12只。UTI组大鼠术毕苏醒即刻经腹腔注射UTI 50 000 U/kg，连续注射7 d，C组和PH组大鼠连续7 d每日腹腔注射等量0.9%氯化钠溶液。3组大鼠于末次给药结束后24 h均进行Morris水迷宫试验和旷场实验等行为学测试，测试完毕后处死大鼠，立即取海马组织冻存备用，采用ELISA法检测海马组织炎性因子IL-1、IL-6、TNF-α水平，Western blotting法检测海马组织Amlyoid-β蛋白、tau蛋白、磷酸化tau-Ser396蛋白的表达。 结果与C组和UTI组比较，PH组大鼠第3、4天的逃避潜伏期、游泳距离均延长（F=11.783、72.141、70.807,均P<0.001），探索时间、穿越次数均缩短（F=143.244、32.428,均P<0.001），中央区探索时间、跨格次数、旷场直立次数均缩短（F=76.232、105.990、17.477,均P<0.001）；海马组织炎症因子TNF-α、IL-6、IL-1的浓度均增加（F=395.545、1 124.503、474.526,均P<0.001），海马组织tau蛋白、磷酸化tau-Ser396蛋白、Amlyoid-β蛋白表达均增加（F=285.764、307.440、557.347,均P<0.001）。 结论UTI可改善PH后老年大鼠的学习记忆能力，其机制可能与UTI抑制海马细胞炎症及Amlyoid-β蛋白、tau蛋白、磷酸化tau-Ser396蛋白的表达有关。

Mechanism of ulinastatin post-treatment on learning and memory function after partial hepatectomyin aged rats

ObjectiveTo investigate the effects of ulinastatin post-treatment on the learning and memory after partial hepatectomy in aged rats. MethodsThirty-six healthy C57BL/6J male mice (weighed 27-36 g) were randomly divided into three groups: control group (group C), partial hepatectomy group (group PH), and ulinastatin post-treatment group (group UTI), with 12 in each group. After being performed partial hepatectomy, 50 000 U/kg ulinastatin was injected intraperitoneally for 7 consecutive days in UTI group, while the equal volume of normal saline was given in group C and group PH. 24 hours after the last injection, the rats underwent Morris water maze and open-filed test. The animals were sacrificed and their hippocampi were immediately removed for determination of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-1 (IL-1) using ELISA and expression of Amloyid-β protein, protein tau, protein tau phospho-396 in the hippicampus of the cells using Western blotting. ResultsCompared with group C and group UTI, the escape latency on the third and fourth day and swimming distance in group PH were significantly prolonged (F=11.783, 72.141, 70.807, all P<0.001), the exploring time and the crossing times were shortened (F=143.244, 32.428, both P<0.001), esidence time in the central district and span numbers, the erect frequency were shortened in the open field (F=76.232, 105.990, 17.477, all P<0.001) , and the expression of TNF-α, IL-6 and IL-1 was up-regulated (F=395.545, 1 124.503, 474.526, all P<0.001), the levels of hippocampal tau protein, tau phospho-396 and Amloyid-β protein were increased in group PH (F=285.764, 307.440, 557.347, all P<0.001). ConclusionUlinastatin can improve the cognitive function after partial hepatectomy in old mice and inhibition of inflammatory responses, the expession of hippocampal tau protein, tau phospho-396 and Amloyid-β proteinin hippocampi is involved in the mechanism.