吡格列酮对异氟醚麻醉引起的老年小鼠认知功能损伤的影响  

Effects of pioglitazone on cognitive impairments induced by isoflurane anesthesia in aged mice

作　　者：曹德雄[1] 李玉娟[1] 王飞[1] 苏兴文[2] 曹林[1] 

机构地区：[1]中山大学孙逸仙纪念医院麻醉科,广东广州510120 [2]中山大学中山医学院药理教研室,广东广州510089

出　　处：《中国病理生理杂志》2014年第6期1059-1065,共7页Chinese Journal of Pathophysiology

基　　金：国家自然科学基金资助项目(No.81371259);广东省自然科学基金资助项目(No.S2013010014898;No.S2013010016207)

摘　　要：目的:研究高选择性的过氧化物酶体增殖物激活受体γ(PPARγ)激动剂吡格列酮(Pi)对异氟醚引起的老年小鼠认知功能障碍和脑内炎症细胞因子的影响。方法:136只11个月大的雄性C57BL/6J小鼠随机分成5组:对照组(Con)、异氟醚组(Iso)、吡格列酮(10 mg/kg)+异氟醚组(Pi10+Iso)、吡格列酮(20 mg/kg)+异氟醚组(Pi20+Iso)和单纯吡格列酮(20 mg/kg)组(Pi20)。各异氟醚处理组的小鼠吸入混合1.4%异氟醚的氧气2 h;Con和Pi20组的小鼠仅吸入氧气2 h。吡格列酮溶于1%的羧甲基纤维素钠(CMC),在小鼠吸入异氟醚或单纯氧气前2 h,按10 mg/kg或20 mg/kg灌胃,Con组和Iso组小鼠仅给予相同容量的1%CMC。在异氟醚处理结束后48h行恐惧记忆实验以检测小鼠的学习记忆功能;6 h时取部分小鼠分离皮质和海马行Western blotting检测PPARγ蛋白及ELISA法检测脑组织IL-1β和TNF-α水平。结果:与Con组比较,Iso组的僵住行为减少(P<0.05),海马IL-1β水平增加(P<0.05);与Iso组比较,Pi10+Iso组的僵住行为和PPARγ蛋白表达无明显变化(P>0.05),而Pi20+Iso组的僵住行为和PPARγ蛋白表达均明显增加(P<0.05)且海马中IL-1β水平降低(P<0.05)。各组海马和皮质TNF-α水平以及皮质中IL-1β水平无明显差异(P>0.05)。结论:吡格列酮可以减轻异氟醚引起的老年小鼠的认知功能障碍,并可以缓解异氟醚引起的小鼠海马IL-1β含量的增加。AIM： To investigate the effects of pioglitazone , a peroxisome proliferator-activated receptor γ（ PPARγ） agonist, on the cognitive impairments and inflammatory cytokine production induced by isoflurane in aged mice . METHODS：Male C57BL/6J mice （ 11-month-old, n =136 ） were assigned randomly into 5 groups： control group （ Con） , isoflurane group （ Iso） , 10 mg/kg pioglitazone ＋isoflurane group （ Pi10＋Iso） , 20 mg/kg pioglitazone ＋isoflu-rane group （Pi20＋Iso） and 20 mg/kg pioglitazone alone group （Pi20）.The mice in all isoflurane-treated groups were exposed to oxygen mixed with 1.4%isoflurane for 2 h.The mice in Con group and in Pi20 group were exposed to oxygen only for 2 h.Pioglitazone was suspended in 1% carboxymethyl cellulose （CMC）.Pioglitazone （10 mg/kg or 20 mg/kg） was gavaged 2 h prior to the exposure of isoflurane or oxygen alone .The same volume of 1% CMC was gavaged in Con group and in Iso group.Fear conditioning tests were performed to determine the learning and memory abilities 48 h after isoflurane exposure.Fresh cerebral cortice and hippocampi were dissected to measure the protein expression of PPAR γby Western blotting, and the contents of IL-1βand TNF-αwere analyzed by ELISA 6 h after isoflurane exposure .RESULTS： Com-pared with Con group, the response of freezing behavior decreased （P〈0.05） and IL-1βcontent in the hippocampus in-creased （ P〈0.05） in Iso group.Compared with Iso group , the response of freezing behavior and PPARγprotein expres-sion level had no significant change （ P〉0.05） in Pi10＋Iso group, but the response of freezing behavior and PPARγprotein expression level increased significantly （P〈0.05） and IL-1βcontent in the hippocampus decreased （P〈0.05） in Pi20＋Iso group.IL-1βcontent in the cerebral cortex and TNF-αlevels both in the cerebral cortex and the hippocampus showed no significant difference among all groups （P〉0.05）.CONCLUSION：Pioglitazone attenuates cognitive impair-ments

关 键 词：异氟醚 认知功能 细胞因子 

分 类 号：R363[医药卫生—病理学]