七氟烷后处理对脑缺血大鼠学习记忆功能和氧化应激反应的影响OACSTPCD
The effect of sevoflurane postconditioning on learning and memory function and oxidative stress in rats with cere-bral ischemia
目的 观察七氟烷(Sevo)后处理对脑缺血再灌注损伤(CIRI)大鼠的学习记忆功能、神经功能及氧化应激反应的影响.方法 选取SPF级健康雄性老年SD大鼠40只,随机分为4组,分别为假手术组(Sham组)、脑缺血再灌注模型组(CIRI组)、2%Sevo后处理组(2%Sevo组)、3%Sevo后处理组(3%Sevo组),每组10只.除Sham组外余下3组采用左颈总动脉夹闭闭塞法构建CIRI大鼠模型.在模型构建后后处理组分别吸入2%、3%Sevo 30 min,Sham组、CIRI组则自主呼吸30 min.恢复灌注24 h后,使用Garcia神经功能评分评估神经功能;恢复灌注72 h后,通过Morris水迷宫实验检测学习记忆能力;随后收集血清并处死大鼠,利用酶联免疫吸附(ELISA)实验检测大鼠血清中的乳酸脱氢酶(LDH)、肌酸磷酸激酶(CK)和超氧化物歧化酶(SOD)及丙二醛(MDA)的活性;收集大鼠缺血侧脑皮质组织,通过ELISA实验检测其中白细胞介素(IL)-1β、IL-6和IL-10浓度.结果 恢复灌注24 h后,CIRI组Garcia评分为(9.932±0.349)分,显著低于Sham组,Sevo后处理组Garcia评分较CIRI组升高,其中2%Sevo组效果显著(P<0.05).恢复灌注72 h后,CIRI组各时段逃避潜伏期显著高于Sham组,穿越平台次数亦显著低于Sham组,Sevo后处理各组各时段逃避潜伏期明显降低、穿越平台次数明显升高,其中2%Sevo浓度组表现明显,差异有统计学意义(P<0.05)o CIRI 组大鼠血清 LDH、CK、MDA 和脑组织 IL-1 β、IL-6、IL-10 水平分别为(614.89±76.48)U/L、(1 369.52±218.03)U/L、(10.68±1.25)nmol/mL 和(2.91±0.48)pg/mg、(2.89±0.69)pg/mg、(11.62±1.94)pg/mg,均显著高于Sham组,血清SOD水平为(89.15±6.12)U/mL,显著低于Sham组,差异均有统计学意义(P<0.05),Sevo后处理组各指标水平趋势与之相反,其中2%Sevo浓度效果显著,差异有统计学意义(P<0.05).结论 七氟烷后处理对CIRI大鼠有明显的脑部保护作用,降低氧化应激反应;并能提高大鼠的学习记忆能力,减轻神经功能损伤与脑内炎症反应,以2%Sevo浓度效果最显著.其疗效机制可能与其抗炎、抗氧化机制有关.
Objective To observe the effects of sevoflurane(Sevo)postconditioning on learning and memory function,neurological function,and oxidative stress response in rats with cerebral ischemia-reperfusion injury(CIRI).Methods Forty healthy male elderly SPF-grade SD rats were randomly divided into four groups:sham operation group(Sham group),cerebral ischemia-reperfusion model group(CIRI group),2%Sevo postconditioning group(2%Sevo group),and 3%Sevo postconditioning group(3%Sevo group),with 10 rats in each group.Except for the Sham group,the other three groups underwent left common carotid artery occlusion to establish the CIRI rat model.After model estab-lishment,the postconditioning groups inhaled 2%and 3%Sevo for 30 minutes,respectively,while the Sham and CIRI groups breathed spontaneously for 30 minutes.After 24 hours of reperfusion,neurological function was assessed using Gar-cia neurological function score;after 72 hours of reperfusion,learning and memory ability were tested using the Morris wa-ter maze experiment.Serum was collected,and the rats were sacrificed.Serum levels of lactate dehydrogenase(LDH),creatine kinase(CK),superoxide dismutase(SOD),and malondialdehyde(MDA)were measured by enzyme-linked immunosorbent assay(ELISA).Ischemic cortical tissue was collected to detect interleukin(IL)-1β,IL-6,and IL-10 levels by ELISA.Results After 24 hours of reperfusion,the Garcia score of the CIRI group was(9.932±0.349)points,which was significantly lower than that of the Sham group,and the Garcia score of the Sevo postconditioning groups was higher than that of the CIRI group,with the 2%Sevo group showing significant improvement(P<0.05).After 72 hours of reperfusion,the escape latency of the CIRI group was significantly higher than that of the Sham group,and the number of platform crossings was significantly lower.The Sevo postconditioning groups showed a significant reduction in escape latency and an increase in platform crossings,with the 2%Sevo group showing significant improvement(P<0.05).Serum levels of LDH,CK,MDA,and brain tissue IL-1β,IL-6,IL-10 in the CIRI group were significantly higher than those in the Sham group[(614.89±76.48)U/L,(1 369.52±218.03)U/L,(10.68±1.25)nmol/mL,(2.91±0.48)pg/mg,(2.89±0.69)pg/mg,(11.62±1.94)pg/mg],while serum SOD levels were significantly lower(89.15±6.12 U/mL),with statistically significant differences(P<0.05).The Sevo postconditioning groups showed trends opposite to those of the CIRI group,with significant effects observed at the 2%Sevo concentration(P<0.05).Conclusion Sevoflurane postconditioning exerts a significant neuroprotective effect on CIRI rats,reducing oxidative stress responses,improving learning and memory abilities,and alleviating neurological damage and brain inflammation.The op-timal effect was observed at a 2%Sevo concentration.The underlying mechanisms may be related to its anti-inflammatory and antioxidant properties.
唐琼琳;姜静静;邓静宜;吴晓峰;卢建旺;李恒
广州医科大学附属清远医院(清远市人民医院)麻醉科(广东清远 511518)广州医科大学(广东广州 510180)
临床医学
七氟烷后处理学习记忆功能氧化应激脑缺血
sevoflurane postconditioninglearning and memory functionoxidative stresscerebral ischemia
《广东医学》 2024 (006)
692-697 / 6
清远市科技计划项目(2022ZCJF)
评论