异氟醚吸入麻醉对大鼠认知功能及海马组织中BDNF、MMP-9、炎症因子表达的影响

Effects of isoflurane inhalation anesthesia on expression of BDNF, MMP-9 and inflammatory factors in hippocampus of rats

目的观察异氟醚(ISO)吸入麻醉对大鼠认知功能及海马组织中脑源性神经营养因子9(BDNF)、基质金属蛋白酶9(MMP-9)、炎症因子表达的影响。方法取54只10周龄健康雄性SD大鼠,采用随机数字表法分为三组各18只;空白组自由吸入空气1 h,对照组吸入40%氧和空气混合气体1 h,ISO组吸入3%ISO麻醉诱导后以1.8%ISO维持麻醉1 h;分别于干预后第1、4、7天行水迷宫实验,观察逃避潜伏期及穿越次数评估认知功能;采集大鼠海马组织标本,比色法检测TNF-α、IL-6、IL-1β,RT-PCR法检测BDNF、MMP-9 mRNA。结果干预第1天,与对照组和空白组比较,ISO组逃避潜伏期延长、穿越平台次数减少,海马组织中TNF-α、IL-6、IL-1β及MMP-9 mRNA表达增加而BDNF mRNA表达减少(P均<0.05);干预第4、7天,三组各指标差异均无统计学意义。结论ISO吸入麻醉会对大鼠认知功能造成短暂伤害,其机制与大鼠海马组织中炎症因子及MMP-9基因表达升高、BDNF基因表达降低有关。

Objective To investigate the effects of isoflurane(ISO)inhalation anesthesia on the cognitive function and the expression of brain-derived neurotrophic factor(BDNF),matrix metalloproteinase 9(MMP-9),and inflammatory factors in rat hippocampus tissues.Methods Fifty-four healthy male SD rats aged 10 weeks were randomly divided into the blank group,control group,and ISO group,with 18 in each group.Rats in the blank group inhaled air freely for 1 hour,rats in the control group inhaled mixture of 40%oxygen and air for 1 hour,and rats in the ISO group inhaled 1.8%for 1 hour after 3%ISO induction of anesthesia.The water maze experiment was conducted on the first,fourth,and seventh days after intervention,respectively;we assessed cognitive function by observing the escape latency and times of passage escape;hippocampal tissue samples were collected to detect the expression of tumor necrosis factor-α(TNF-α),IL-6,IL-1β,BDNF and MMP-9 mRNA by colorimetry.Results On the first day of intervention,compared with the control group and the blank group,the escape latency was prolonged,the number of crossing platforms decreased,and the expression of TNF-α,IL-6,IL-1βand MMP-9 mRNA in the hippocampus increased and the expression of BDNF mRNA decreased in the ISO group(all P<0.05);on the 4th and 7th days of intervention,there was no significant differences in the indexes among the three groups(all P>0.05).Conclusion ISO inhalation anesthesia can cause temporary damage to cognitive function in rats,and its mechanism is related to the increase of inflammatory factors and MMP-9 gene expression in hippocampus and the decrease of BDNF gene expression.