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  

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

作　　者：洪玉[1] 刘嘉羿 王寿平[2] 张磊[3] Hong Yu;Liu Jiayi;Wang Shouping;Zhang Lei(Department of Anesthesialogy,3Department of Hepatobiliary Surgery,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China;Department of Anesthesialogy,the Third Affiliated Hospital of Guangzhou Medical University,Guangzhou 510150,China)

机构地区：[1]中山大学孙逸仙纪念医院麻醉科,广州510120 [2]广州医科大学附属第三医院麻醉科,510150 [3]中山大学孙逸仙纪念医院肝胆外科,广州510120

出　　处：《中华普通外科学文献（电子版）》2018年第5期310-313,共4页Chinese Archives of General Surgery(Electronic Edition)

基　　金：国家自然科学基金面上项目(81271223);广东省自然科学基金资助项目(2017A030313871)

摘　　要：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-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-蛋白、tau蛋白、磷酸化tau-Ser396蛋白的表达有关。Objective To investigate the effects of ulinastatin post-treatment on the learning and memory after partial hepatectomy in aged rats. Methods Thirty-six healthy C57 BL/6 J 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. Results Compared with group C and group UTI, the escape latency on the third and fourth day and swimming distance in group PH weresignificantly 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）. Conclusion Ulinastatin 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.

关 键 词：肝切除术 大鼠 学习 记忆 乌司他丁 

分 类 号：R614[医药卫生—麻醉学]