七氟醚通过上调MicroRNA-96影响大鼠认知障碍的效果与机制研究

Effect and mechanism of sevoflurane on up-regulating microRNA-96 in regulating cognitive impairment

目的探讨七氟醚通过上调MicroRNA-96(miR-96)影响大鼠认知障碍的效果与机制。方法健康清洁级雄性SD大鼠15只随机数字表法分为3组,每组5只,分别为对照组、七氟醚暴露4 h组(实验1组)、七氟醚暴露8h组(实验2组),对照组在相同的环境下吸入2 L/min氧气8 h,实验1组停止吸入七氟醚后吸入2 L/min氧气4 h。采用水迷宫实验测定大鼠认知功能,检测不同时间点的认知功能、血气指标、体温、血清IGF-1水平和miR-96表达情况。结果实验1组与实验2组麻醉后3 d、7 d与14 d的逃避潜伏期显著高于对照组,目标象限累计时间低于对照组,比较差异有统计学意义(P <0. 05),实验1组与实验2组比较差异也有统计学意义(P <0. 05)。三组大鼠PaO_2与体温在麻醉前、麻醉4 h与麻醉8 h的组内与组间比较差异无统计学意义(P> 0. 05)。实验1组与实验2组麻醉后3 d、7d与14 d的血清IGF-1含量均显著低于对照组(P <0. 05),实验2组显著低于实验1组(P <0. 05)。实验1组与实验2组麻醉后7 d海马组织的miR-96相对表达量显著低于对照组(P <0. 05),实验2组显著低于实验1组(P <0. 05)。结论七氟醚能通过上调大鼠海马组织miR-96的表达,抑制血清IGF-1的表达,从而损伤大鼠的认知功能,且七氟醚暴露8 h较暴露4 h对其损伤更明显。

Objective To investigate the effect and mechanism of sevoflurane on up-regulating microRNA-96(miR-96)in regulating cognitive impairment in rats.Methods 15 healthy and clean male SD rats were randomly divided into 3 groups,5 rats in each groups,including the control group,sevoflurane exposed for 4 h(experiment group 1)and sevoflurane exposed for 8 h(experiment group 2),the control group were inhaled 2 L/min oxygen for 8 hours under the same environment,and the experimental group 1 stopped inhaling sevoflurane and inhaled 2 L/min oxygen for 4 hours.The water maze test were used to determine the cognitive function of the rats,and the miR-96 expression were detected.Results The escape latency of the experimental group 1 and the experimental group 2 were significantly higher than that of the control group at 3 d,7 d and 14 d after anesthesia.The cumulative time of the target quadrant were lower than that of the control group with statistically significant difference(P<0.05)).There were no significant difference in PaO2 and body temperature compared among the three groups before the anesthesia,4 h anesthesia and 8h anesthesia(P>0.05).The levels of serum IGF-1 in the experimental group 1 and the experimental group 2 were significantly lower than those in the control group at 3 d,7 d and 14 d after anesthesia(P<0.05).The experimental group 2 were significantly lower than the experimental group 1(P<0.05).The relative expression of miR-96 in hippocampus at 14 d after anesthesia of experimental group 1 and experimental group 2 were significantly lower than that of the control group(P<0.05).The experimental group 2 were significantly lower than the experimental group 1(P<0.05).Conclusion Sevoflurane can up-regulate the expression of miR-96 in rat hippocampus and inhibit the expression of serum IGF-1,thus impairing the cognitive function of rats.And the sevoflurane exposure for 8 h is more obvious than the exposure for 4 h.