摘要
目的:探讨miR-34a/沉默信息调节蛋白1(miR-34a/SIRT1)通路在七氟醚麻醉致老年大鼠神经损伤中的作用。方法:将24只雄性老年大鼠随机分为对照组、模型组、miR-34a抑制剂(antagomiR)组及antagomiR-NC组,每组6只;造模前,antagomiR组及antagomiR-NC组分别注射20μmol/L的miR-34a antagomiR或miR-34a antagomiR-NC试剂(5ml/kg),对照组和模型组注射等体积的生理盐水,连续注射5d;除对照组外其余组均建立七氟醚麻醉致神经损伤大鼠模型;采用Morris水迷宫测定大鼠认知功能,qRT-PCR检测海马组织中miR-34a、SIRT1表达水平,Western blot检测相关蛋白表达。结果:与对照组比,模型组的逃避潜伏期、miR-34a、p53、caspase-3、Bax水平均显著增加(P<0.05),穿越平台次数、Bcl-2及SIRT1水平均显著降低(P<0.05);与模型组比,antagomiR组的逃避潜伏期、miR-34a、p53、caspase-3、Bax水平均明显降低(P<0.05),穿越平台次数、Bcl-2与SIRT1水平明显增加(P<0.05),而antagomiR-NC组以上指标无显著变化(P>0.05)。结论:七氟醚可通过激活miR-34a/SIRT1通路,促进大鼠神经组织损伤,通过靶向调控SIRT1的表达水平可能是七氟醚麻醉致老年大鼠神经损伤的作用机制。
Objective:To investigate the role of miR-34a/silenced information regulatory protein 1(miR-34a/SIRT1)pathway in nerve injury induced by sevoflurane anesthesia in aged rats.Methods:24 male aged rats were randomly divided into control group,model group,antagomiR(miR-34a inhibitor)group and antagomirR-NC group,with 6 rats in each group.Before modeling,antagomiR group and antagomirR-NC group were injected with 20μmol/L miR-34a antagomiR or miR-34a antagomirR-NC reagent(5ml/kg),respectively,while control group and model group were injected with the same volume of normal saline for 5 consecutive days.Except for the control group,sevoflurane anesthesia induced nerve injury rat model was established.Morris water maze was used to measure the cognitive function of rats.qRT-PCR was used to detect the expression levels of miR-34a and SIRT1 in hippocampus,and Western blot was used to detect the expression of related proteins.Results:Compared with the control group,the escape latency,miR-34a,p53,caspase-3 and Bax levels in the model group were significantly increased(P<0.05),and the times of crossing the platform,Bcl-2 and SIRT1 levels were significantly decreased(P<0.05).Compared with the model group,the escape latency,miR-34a,p53,caspase-3 and Bax levels in the antagomiR group were significantly decreased(P<0.05),and the times of crossing the platform,Bcl-2 and SIRT1 levels were significantly increased(P<0.05).However,antagomirR-NC group had no significant changes in the above indexes(P>0.05).Conclusion:Sevoflurane can promote nerve tissue injury in rats by activating miR-34a/SIRT1 pathway,which may be the mechanism of sevoflurane anesthesia induced nerve injury in aged rats by targeting SIRT1 expression level.
作者
李洪影
祁向雯
毛珊珊
庞红利
LI Hongying;QI Xiangwen;MAO Shanshan(Department of Anesthesia and Perioperative Medicine,the First Affiliated Hospital of He’nan University,Kaifeng City,He’nan Province 475000)
出处
《医学理论与实践》
2023年第6期901-904,共4页
The Journal of Medical Theory and Practice
