CAJ | 학술논문

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48 h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。
목적：연구고선택성적과양화물매체증식물격활수체γ（ PPARγ）격동제필격렬동（ Pi）대이불미인기적노년소서인지공능장애화뇌내염증세포인자적영향。방법：136지11개월대적웅성C57BL／6J소서수궤분성5조：대조조（Con）、이불미조（Iso）、필격렬동（10 mg／kg）＋이불미조（Pi10＋Iso）、필격렬동（20 mg／kg）＋이불미조（Pi20＋Iso）화단순필격렬동（20 mg／kg）조（Pi20）。각이불미처리조적소서흡입혼합1.4％이불미적양기2 h；Con화Pi20조적소서부흡입양기2 h。필격렬동용우1％적최갑기섬유소납（CMC），재소서흡입이불미혹단순양기전2 h，안10 mg／kg혹20 mg／kg관위，Con조화Iso조소서부급여상동용량적1％CMC。재이불미처리결속후48 h행공구기억실험이검측소서적학습기억공능；6 h시취부분소서분리피질화해마행Western blotting 검측PPARγ단백급ELISA법검측뇌조직IL-1β화TNF-α수평。결과：여Con조비교，Iso조적강주행위감소（P＜0.05），해마IL-1β수평증가（P＜0．05）；여Iso조비교，Pi10＋Iso조적강주행위화PPARγ단백표체무명현변화（P＞0．05），이Pi20＋Iso조적강주행위화PPARγ단백표체균명현증가（P＜0．05）차해마중IL-1β수평강저（P＜0．05）。각조해마화피질TNF-α수평이급피질중IL-1β수평무명현차이（P＞0．05）。결론：필격렬동가이감경이불미인기적노년소서적인지공능장애，병가이완해이불미인기적소서해마IL-1β함량적증가。
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 ex-posed 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 PPARγpro-tein 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 and the elevates the level of IL-1βin the hippocampus induced by isoflurane in aged mice .