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毒扁豆碱对异氟醚麻醉大鼠认知功能的影响
Effect of Physostigmine Combined with Isoflurane Anesthesia on Cognitive Function in Rats
【作者】 杨锋;
【导师】 李玉兰;
【作者基本信息】 兰州大学 , 麻醉医学, 2015, 硕士
【摘要】 目的探讨毒扁豆碱对异氟醚麻醉后大鼠海马炎性反应、caspase-3表达及认知功能的影响。方法18月龄SD大鼠80只,体重400~450g,随机分为4组(n=20):对照组(C组)吸入含有30%氧气的空氧混合气体6h;异氟醚组(I组)吸入1.4%的异氟醚6h;毒扁豆碱组+异氟醚组(PI组)与毒扁豆碱组(P组)腹腔注射毒扁豆碱100μg/kg,每8h一次,共3次。首次给药后,PI组吸入1.4%的异氟醚6h,P组吸入同浓度载气6h。麻醉结束行动脉血气分析,12h后取海马组织Elisa法检测TNF-α、IL-1β、IL-6含量、RT-PCR法检测capase-3mRNA的表达。显微镜观察海马CA1区锥体细胞形态变化;麻醉后第2-7天评估认知功能。结果四组间血气水平无统计学差异(P>0.05)。与C组、P组比较,I、PI组IL-1β、IL-6含量及capase-3mRNA水平升高,逃避潜伏期延长,探索时间缩短(P<0.05),海马CA1区锥体细胞凋亡增多;与I组比较,PI组IL-1β、IL-6含量及capase-3mRNA表达降低(P<0.05),逃避潜伏期缩短,探索时间延长(P<0.05),CA1区锥体细胞凋亡减少。P组与C组无统计学差异(P>0.05)。TNF-α在四组间无统计学差异(P>0.05)。结论毒扁豆碱可改善异氟醚麻醉引起的大鼠认知功能损害,其机制可能与抑制海马炎性反应及神经元凋亡有关。
【Abstract】 Objective To evaluate the effect of physostigmine on isflurane induced cognition deficit and inflammatory response, caspase-3 expression in hippocampus in rats.Methods eighty 18-month-old male Sprague-Dawley rats, weighing 400-450g, were randomly assigned into 4 groups (n=20 each):Control groups (groups C), isoflurane groups (group I), physostigmine+isoflurane group (group PI), and physostigmine (group P). Group C inhaled a gas mixture of oxygen and air for 6 h and group I inhaled 1.4%isoflurane for 6 h; Physostigmine 100 ug/kg was injected intraperitoneally every 8 h, totally 3 times in the group PI and group P; After the first injection,1.4% isoflurane was inhaled to the rats of group PI and same concentration of oxygen and air was inhaled to the rats of group P for 6h. Blood samples were taken immediately after the end of anesthesia for blood gas analysis. Hippocampi were isolated 12h after the end anesthesia for determination of TNF-α、IL-1β、 and IL-6 contents by ELISA and caspase-3mRNA expression by RT-PCR. The pyramid cells of hippocampi were observed for the pathological change. The cognitive function was assessed during the 2nd to 7th day after the end of anesthesia.Results There were no significant differences in the parameters of arterial blood gas analysis and blood glucose level among the 4 groups(P>0.05). Compared with group C and group P, the contents of IL-1β、and IL-6 in group I and PI were increased, the expression of caspase-3 was up-regulated, and the escape latency at 4-6d was prolonged, the probe time was shortened in group I and group PI (p<0.05), the number of apoptosis cells were increased. Compared with group I, the contents of IL-1β、IL-6 in group PI were decreased, the expression of caspase-3 was down-regulated, and the escape latency was shortened, the probe time was prolonged in group PI(P<0.05), the number of apoptosis cells were reduced than group I. There were no significant difference of the content TNF-α between four groups.Conclusion Physostigmine can improve isoflurane induced cognitive function in adult rats, which may be related to inhibition of inflammatory response and neuron apoptosis of the hippocampus.
【Key words】 Physostigmine; Isoflurane; Inflammation; Apoptosis; Cognition;