异氟醚对β淀粉样蛋白诱导的大鼠PC12细胞凋亡和内质网应激的影响及其机制  

Influence of isoflurane in apoptosis and endoplasmic reticulum stress of PC12 cells induced by Aβ25-35 of rats and its mechanism

作　　者：邹泳国 周春燕[1] 朴美花[1] 刘楠[1] 岳云[3] 冯春生[1] 

机构地区：[1]吉林大学第一医院麻醉科,吉林长春130021 [2]吉林省国健妇产医院麻醉科,吉林长春130062 [3]首都医科大学附属北京朝阳医院麻醉科,北京100020

出　　处：《吉林大学学报（医学版）》2014年第2期224-228,I0001,共6页Journal of Jilin University：Medicine Edition

基　　金：国家自然科学基金资助课题(81141065;81271215)

摘　　要：目的:探讨异氟醚对β淀粉样蛋白(Aβ)25-35诱导的大鼠PC12细胞凋亡和内质网应激(ERS)的影响,并阐明其作用机制。方法:将PC12细胞随机分为正常对照组、10μmol·L-1 Aβ25-35组(Aβ组)、2%异氟醚组(Iso组)和2%异氟醚联合10μmol·L-1 Aβ25-35组(Iso+Aβ组)。MTT法检测各组PC12细胞存活率;Hoechst 33342核染色法检测各组PC12细胞凋亡形态;Western blotting法检测各组PC12细胞内质网分子伴侣葡萄糖调节蛋白78(GRP78)、ERS相关凋亡信号蛋白C/EBP同源蛋白(CHOP)、磷酸化氨基末端蛋白激酶(p-JNK)和caspase-12表达量。结果:与正常对照组比较,Aβ组和Iso组PC12细胞存活率明显降低(P<0.05),细胞凋亡率明显增加(P<0.05),GRP78表达量明显上调(P<0.05),ERS相关凋亡信号蛋白CHOP、p-JNK和caspase-12表达量均明显增加(P<0.05);与Aβ组比较,Iso+Aβ组PC12细胞存活率明显降低(P<0.05),细胞凋亡率明显增加(P<0.05),GRP78、CHOP、p-JNK和caspase-12表达量均明显增加(P<0.05)。结论:异氟醚能够促进Aβ25-35诱导的大鼠PC12细胞凋亡,其机制与激活ERS及其相关的凋亡信号通路有关联。Objective To explore the influence of isoflurane in apoptosis and endoplasmic reticulum stress （ERS） of PC12 cells of the rats induced by amyloid β-protein 25-35 （Aβ25-35）, and to clarify its mechanism. Methods The PC12 cells were randomly divided into normal control group, 1010μm01·L^-1 Aβ25-35 group （Aβ group）, 2% isoflurane group （Iso group）, and 2% isoflurane combined with 10 10μm01·L^-1 Aβ25-35 group（Iso＋Aβ group）. The survival rates of the PC12 cells in various groups were determined by MTT assay; the apoptotic morphology of the PC12 cells was detected by Hoechst 33342 staining method; Western blotting method was performed to observe the expression levels of endoplasmic reticulum molecular chaperone glucose regulation protein 78（GRP78） and ERS associated apoptosis signal protein C/EBP homologous protein（CHOP）, phosphorylated amino terminal protein kinase（p-JNK）, and caspase-12 of PC12 cells. Results Compared with normal control group, the survival rates of the PC12 cells in A]3 group and Iso group were decreased significantly（P〈0.05）, but the apoptotic rates of the PC12 cells were significantly increased （P〈0.05）, the expression levels of GRP78 and ERS associated apoptotic signal protein CHOP, p-JNK and caspase-12 were increased significantly （P〈0.05）. Compared with AI3 group, the survival rate of the PC12 cells in Iso＋A]3 group was decreased significantly（P〈0.05）, and the apoptotic rate was significantly increased （P〈0.05）, and the expression levels of GRP78, CHOP, p-JNK, and caspase-12 were increased significantly （P〈0.05）. Oonclusion Isoflurane could aggravate the apoptosis of PC12 cells of the rats induced by Aβ25-35, and the mechanism may be involved in activation of ERS and ERS associated apoptosis signal pathway.

关 键 词：异氟醚 阿尔茨海默病 PC12细胞 内质网应激 细胞凋亡 

分 类 号：R614.24[医药卫生—麻醉学]