乌司他丁对手术创伤致大鼠术后认知功能障碍的影响及相关机制研究

doi:10.3969/j.issn.10073205.2019.07.023

摘要/Abstract

摘要： ［摘要］〓
〖HTH〗目的〖HTSS〗〖KG*2〗探讨乌司他丁对手术创伤致大鼠术后认知功能障碍（postoperative cognitive dysfunction, POCD）的影响及作用机制。
〖HTH〗方法〖HTSS〗〖KG*2〗将 60只Wistar大鼠随机分为对照组、POCD组、乌司他丁组各20只。术前5 d先行空间获得性实验学习。对照组注射生理盐水；POCD组行全身麻醉脾切除术制备POCD模型，注射生理盐水；乌司他丁组在制备POCD模型前后注射乌司他丁。术后3，7 d，评估各组大鼠的行为学变化；测定海马及前额皮层组织中丙二醛（malondialdehyde,MDA）、超氧化物歧化酶（superoxide dismutase,SOD）、肿瘤坏死因子α（tumor necrosis factorα，TNFα）、白细胞介素1β（interleuken1β，IL1β）及核因子κB（nuclear factorkappa B，NFκB）的含量。
〖HTH〗结果〖HTSS〗〖KG*2〗术后3 d，POCD组大鼠停留时间短于对照组，穿台次数少于对照组，工作记忆潜伏时间长于对照组，MDA含量高于对照组，SOD含量低于对照组，POCD组大鼠TNFα、IL1β和NFκB水平均高于对照组（P＜005）；乌司他丁组大鼠停留时间短于对照组，长于POCD组，穿台次数多于POCD组，工作记忆潜伏时间长于对照组，短于POCD组，MDA含量高于对照组，低于POCD组，SOD含量低于对照组，高于POCD组，TNFα、IL1β和NFκB水平均高于对照组，低于POCD组（P＜005）。术后7 d，对照组和乌司他丁组大鼠停留时间短于术后3 d，工作记忆潜伏时间长于术后3 d，对照组和乌司他丁组MDA含量高于术后3 d，POCD组MDA含量低于术后3 d，对照组SOD含量低于术后3 d，POCD组乌司他丁组MDA含量高于术后3 d，POCD组和乌司他丁组TNFα水平低于术后3 d，3组IL1β和NFκB水平低于术后3 d（P＜005）；POCD组大鼠停留时间短于对照组，工作记忆潜伏时间长于对照组，乌司他丁组大鼠停留时间短于对照组，长于POCD组，工作记忆潜伏时间长于对照组，短于POCD组，POCD组大鼠MDA含量高于对照组，SOD含量低于对照组，乌司他丁组大鼠MDA含量高于对照组，低于POCD组，SOD含量低于对照组，高于POCD组，POCD组大鼠TNFα、IL1β和NFκB水平均高于对照组，乌司他丁组IL1β水平低于POCD组（P＜005）。
〖HTH〗结论〖HTSS〗〖KG*2〗乌司他丁通过清除氧自由基、抑制炎症反应，可以改善POCD，具有积极的作用。

关键词: 认知障碍, 乌司他丁, 手术后并发症, 大鼠

Abstract: ［Abstract］〓Objective〖HTSS〗〓To observe the protective effect of ulinastatin on the postoperative cognitive dysfunction(POCD) impairment and to explore its specific mechanism of action in the pathogenesis of disease.
〖HTH〗〖WTHZ〗Methods〖HTSS〗〓Wistar rats were randomly divided into control group, POCD group, ulinastatin group, preoperative 5 days of space acquired experimental study. The control group was injected with normal saline; the POCD group was injected with normal saline after splenectomy under general anesthesia; and the ulinastatin group was injected with ulinastatin before and after the preparation of POCD model. The behavioral changes of rats in each group were evaluated 3 and 7 days after operation. The contents of malondialdehyde(MDA), superoxide dismutase(SOD), tumor necrosis factorα(TNFα), interleukin1β(IL1β) and nuclear factorκB(NFκB) in hippocampus and prefrontal cortex were measured.
〖HTH〗〖WTHZ〗Results〖HTSS〗〓Three days after operation, the rats in POCD group had longer residence time, fewer times to cross the platform, longer working memory latency, higher MDA content and lower SOD content than those in the control group. The levels of TNFa, IL1β and NFκB in POCD group were higher than those in the control group（P＜0.05）. The retention time of rats in ulinastatin group was shorter than that in control group and longer than that in POCD group. The rats in ulinastatin group had more times of perforation, longer working memory latency, shorter working memory latency than POCD group. The rats in ulinastatin group had higher MDA content than control group, lower SOD content than control group, higher SOD content than POCD group. The rats in ulinastatin group had higher TNFa, IL1β and NFκB levels than control group, had lower those than POCD group(P＜005). At 7 days after surgery, the residence time of the control group and the ulinastatin group was shorter than that at the 3 days after surgery, and the working memory latency was longer than that at the 3 days after surgery. At 7 days after surgery, the MDA content in the control group and ulinastatin group was higher than that in the 3 days after surgery，the MDA content in the POCD group was lower than that at the 3 days after surgery. At 7 days after surgery, the SOD content of the control group was lower than that at the 3 days after surgery， the MDA content in the ulinastatin group of the POCD group was higher than that of the postoperative 3 days. At 7 days after surgery, the levels of TNFα in the POCD group and ulinastatin group were lower than those at 3 days after surgery，the levels of IL1β and NFκB in the three groups were lower than those in the 3 days after surgery(P＜005).The residence time of the rats in the POCD group was shorter than that of the control group, and the latency of working memory was longer than that of the control group. The residence time of the rats in the ulinastatin group was shorter than that of the control group and longer than that of the POCD group. The working memory latency was longer than that of the control group and shorter than the POCD group. The MDA content in the POCD group was higher than that in the control group, and the SOD content was lower than that in the control group. The MDA content in the ulinastatin group was higher than that in the control group, and the SOD content was lower than that in the control group, which was higher than the POCD group. The levels of TNFα, IL1β and NFκB in the POCD group were higher than those in the control group. The level of IL1β in the ulinastatin group was lower than that in the POCD group(P＜005).
〖HTH〗〖WTHZ〗Conclusion〖HTSS〗〓Ulinastatin has a positive effect on improving postoperative cognitive dysfunction by scavenging oxygen free radicals and inhibiting inflammatory responses.

Key words: cognition disorders； ulinastatin, postoperative complications； rats

都义日1，刘〓斌2，郎海云1，李常胜1，李鸿斌1，解雅英1*. 乌司他丁对手术创伤致大鼠术后认知功能障碍的影响及相关机制研究[J]. 河北医科大学学报, doi: 10.3969/j.issn.10073205.2019.07.023.

DU Yiri1， LIU Bin2, LANG Haiyun1， LI Changsheng1， LI Hongbin1， XIE Yaying1*. Effects of Ulinastatin on postoperative cognitive dysfunction and related mechanisms in rats after surgical trauma#br#[J]. Journal of Hebei Medical University, doi: 10.3969/j.issn.10073205.2019.07.023.

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乌司他丁对手术创伤致大鼠术后认知功能障碍的影响及相关机制研究

Effects of Ulinastatin on postoperative cognitive dysfunction and related mechanisms in rats after surgical trauma#br#

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