异甘草素预处理对老龄大鼠全身麻醉后认知功能及相关脑区蛋白表达的影响

Effects of isoliquiritigenin preconditioning on cognitive function and protein expressions in relevant brain regions among aged rats after general anesthesia

目的探讨异甘草素预处理对老龄大鼠全身麻醉后认知功能及相关脑区蛋白表达的影响。方法将30只老龄雄性SD大鼠随机分为对照组、手术组、预处理组,每组10只。对照组大鼠不给予任何处理;手术组大鼠腹腔注射75 mg/kg氯胺酮+5 mg/kg咪达唑仑进行麻醉,并行剖腹探查术;预处理组大鼠给予15 mg/kg异甘草素灌胃,60 min后进行麻醉及剖腹探查,方法同手术组。麻醉苏醒1 d后采用水迷宫法评价各组大鼠的学习记忆能力,蛋白质印迹法检测大鼠海马、前额叶皮层和伏隔核中磷酸化环磷酸腺苷结合蛋白(p-CREB)、即刻早期基因c-fos蛋白的表达水平。结果与手术组比较,对照组及预处理组的逃避潜伏时间缩短,目标象限停留时间延长(P<0.05),相关脑区p-CREB、c-fos的蛋白表达水平升高(P<0.05);预处理组与对照组以上指标比较,差异均无统计学意义(P>0.05)。结论异甘草素能够改善老龄大鼠全身麻醉后学习记忆能力,这可能与其改善老龄大鼠相关脑区p-CREB、c-fos的蛋白表达水平有关。

Objective To investigate the effects of isoliquiritigenin preconditioning on the cognitive function and protein expressions in relevant brain regions among aged rats after general anesthesia. Methods Thirty aged male SD rats were randomly divided into control group（ n =10）,operation group（ n =10）and preconditioning group（ n =10）.The control group was not given any treatment;the operation group received intraperitoneal injection of 75 mg/kg ketamine ＋ 5 mg/kg midazolam for anesthesia as well as exploratory operation and laparotomy .The preconditioning group accepted 15 mg/kg isoliquiritigenin by gavage for 60 minutes,then received exploratory operation and laparotomy as the procedures in the operation group.Water maze test was used to assess the abilities of learning and memory in the rats after 1 day of anesthesia recovery,and Western blotting was used to detect the expression levels of hippocampal,prefrontal cortex and nucleus accumbens phosphorylated cyclic adenosine monophosphate response element binding protein（p-CREB） and immediate early gene c-fos protein . Results The control group and preconditioning group had less escape latency,prolonged target quadrant time,and elevated expression levels of p-CREB and c-fos proteins in the related brain regions compared to the operation group（all P 〈0.05）;the indices above showed no statistically significant differences between the control group and the preconditioning group（ P 〉0.05）. Conclusion Isoliquiritigenin can improve the abilities of learning and memory of aged rats after general anesthesia,which is probably related to improving the expression levels of p-CREB and c-fos proteins in the relevant brain regions.