摘要
目的探讨七氟醚麻醉对肺癌大鼠JAK/STAT信号通路的影响及脑神经损伤作用。方法24只健康雄性SD大鼠采用尾静脉注射Walker-256癌细胞悬液法建立大鼠肺癌模型,造模完成后将大鼠随机分为4组,每组6只,分别为模型组、七氟醚A组、七氟醚B组、七氟醚C组;然后七氟醚A、B、C组吸入3%七氟醚+2 ml/min氧气,吸入持续时间分别为4、6、8 h,模型组吸入空气,持续吸入时间6 h,麻醉结束24 h后,测定大鼠血清TNF-α、IL-6及IL-1β水平,利用Morris水迷宫考察大鼠学习及记忆能力,实时定量PCR检测大鼠海马组织caspase-3和caspase-12 mRNA水平,Western blot检测大鼠肺组织中JAK2、STAT3、p-JAK2及p-STAT3水平。结果肺癌大鼠持续吸入不同时间的七氟醚进行麻醉后,与模型组相比,七氟醚各麻醉组肺癌大鼠血清TNF-α、IL-6及IL-1β水平均显著升高(P<0.05),肺癌大鼠逃避潜伏期及首次穿过平台时间均显著延长(P<0.05),90 s内穿过平台的次数显著减少(P<0.05),海马组织caspase-3、caspase-12 mRNA水平均显著升高(P<0.05),肺组织JAK2、STAT3水平均显著升高(P<0.05),JAK2及STAT3磷酸化比例显著增加(P<0.05)。结论七氟醚麻醉能够激活肺癌大鼠JAK/STAT信号通路,并可能通过促进肺癌大鼠海马体凋亡基因的表达引起大鼠脑神经损伤,影响肺癌大鼠学习及记忆能力。
Objective To study the effects of sevoflurane anesthesia on JAK/STAT signaling pathway and cerebral nerve injury in the rats with lung cancer.Methods Twenty-four healthy male SD rats were randomly divided into four groups(n=6 each):model group,sevoflurane group A,sevoflurane group B and sevoflurane group C.All the rats received tail vein injection of Walker-256 cancer cell suspension to establish lung cancer models.Then the rats in sevoflurane group A,B and C inhaled 3%sevoflurane+2 ml/min oxygen for 4 h,6 h and 8 h,respectively.The model group inhaled air for 6 h.And 24 hours after anesthesia,the levels of serum tumor necrosis factor(TNF)-α,interleukin(IL)-6 and IL-1βwere measured,the learning and memory abilities of the rats were measured by Morris water maze,and the levels of caspase-3 and caspase-12 mRNA in the hippocampus were measured by quantitative real-time polymerase chain reaction(qRT-PCR).The levels of JAK2,STAT3,p-JAK2 and p-STAT3 in the lung tissues of the rats were detected by Western blotting.Results Compared with the model group,after continuous inhalation of sevoflurane,the levels of serum TNF-α,IL-6 and IL-1βwere significantly higher(P<0.05),the number of rats crossing the platform within 90 s was significantly decreased(P<0.05),the levels of caspase-3 and caspase-12 mRNA in the hippocampus were significantly increased(P<0.05),the escape latency and the first crossing time were significantly prolonged(P<0.05),the levels of JAK2 and STAT3 in the lung tissues were significantly increased,and the phosphorylation of JAK2 and STAT3 were significantly increased in the sevoflurane-anesthesized rats(P<0.05).Conclusion Sevoflurane anesthesia can activate the JAK/STAT signaling pathway in the lung cancer rats,and may induce cerebral nerve injury and affect the learning and memory abilities of lung cancer rats through promoting the expression of apoptotic genes in the hippocampus.
作者
喻晶晶
易菲妮
卢承志
易云峰
张文龙
陈俊
Yu Jingjing;Yi Feini;Lu Chengzhi;Yi Yunfeng;Zhang Wenlong;Chen Jun(Department of Anesthesiology,909 th Hospital,Joint Logistics and Security Force,Chinese People′s Liberation Army,Zhangzhou 363000,China)
出处
《中华肺部疾病杂志（电子版）》
CAS
2019年第6期708-712,共5页
Chinese Journal of Lung Diseases(Electronic Edition)
基金
2017年度军队后勤科研面上项目(CWH17J030)
