七氟醚联合氧化亚氮吸入麻醉致脑功能下降与CREB信号通路的关系

Relationship of impaired brain function after sevoflurane-nitrous oxide anesthesia and CREB signal pathway

目的探讨七氟醚联合氧化亚氮急诊吸入麻醉致脑功能下降与环腺苷酸应答元件结合蛋白(CREB)相关信号通路的关系。方法选取2014年1月至2017年4月我院急诊科收治的442例患者作为研究对象,按照麻醉方式的不同分为3组,吸入麻醉组患者118例,局部麻醉组患者206例,对照组118例,比较其血液中环磷酸腺苷(cAMP)含量,采用简易智力状态检查量表(MMSE)评分。同时,将60只大鼠随机分为麻醉组(n=30)和对照组(n=30),采用Morris水迷宫实验评价2组大鼠学习记忆功能,测定cAMP、CREB表达情况。结果吸入麻醉组患者血液cAMP浓度、MMSE评分较吸入前显著下降(P<0.05);定位航行试验中,麻醉组大鼠找到平台时间较对照组长,穿越平台次数较对照组少,2组比较差异有统计学意义(P<0.05);Western blot检测结果显示麻醉组大鼠cAMP、p-CREB蛋白表达均低于对照组,差异有统计学意义(P<0.05)。结论七氟醚联合氧化亚氮吸入麻醉致脑功能下降或通过增加核内第二信使CAMP/Ca^(2+)通路,介导CREB表达降低所致。

Objective To explore the relationship of impaired brain function after emergency inhalation anesthesia of sevoflurane combined with nitrous oxide and cyclic AMP response element binding protein （CREB） signal pathway. Methods A total of 442 patients who were admitted into our hospital from January 2014 to April 2017 were selected as the object of this study. And these patients were divided into 3 groups according to different anesthesia ways, namely the inhalation anesthesia group （118 cases）, the local anesthesia group （206 cases）, and the control group （118 cases）. The blood cyclic adenosine monophosphate （cAMP） concentration were examined by the mini mental state examination （MMSE） score scale. At the same time, the 60 rats were randomly divided into the anesthesia group（ n = 30） and the control group（ n = 30）. The learning and memory function of the two groups were evaluated by Morris water maze test, and the expressions of cAMP and CREB were measured. Results The blood cAMP concentration and MMSE score in the inhalation anesthesia group were significantly decreased after inhalation anesthesia（P 〈0.05）. In the place navigation test, rats of the anesthesia group cost much more time to find the platform compared with rats in the control group, and rats of the anesthesia group encountered less times of crossing the platform compared with rats in the control group, and the difference was significant （ P 〈 0.05 ）. Western blot showed that patients of the anesthesia group had lower cAMP and expression of p-CREB protein, with significant difference （P 〈 0.05 ）. Conclusion Brain function decline after sevoflurane inhalation anesthesia combined with nitrous oxide may induced by increasing the nucleus of the second messenger CAMP/Ca^2＋ pathway and decreasing the expression of CREB.