吉林大学学报(医学版)

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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

邹泳国1,2,周春燕1,朴美花1,刘楠1,岳云3,冯春生1   

  1. (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)
  • 收稿日期:2013-10-11 出版日期:2014-03-28 发布日期:2014-03-28
  • 通讯作者: 冯春生 E-mail:fcs1971@hotmail.com
  • 作者简介:邹泳国(1979-),男,吉林省长春市人,主治医师,在读医学硕士,主要从事全麻药对阿尔茨海默病发病机制影响的研究。
  • 基金资助:

    国家自然科学基金资助课题(81141065,81271215)

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

ZOU Yong-guo1,2,ZHOU Chun-yan1,PIAO Mei-hua1,LIU Nan1,YUE Yun3,FENG Chun-sheng1   

  1. (1. Department of Anesthesiology,First Hospital,Jilin University,Changchun 130021,China;2. Department of Anesthesiology,Jilin Guojian Obstetrics and Gynecology Hospital,Changchun 130062,China;3. Department of Anesthesiology,Affiliated Beijing Chaoyang Hospital,Capital University of Medical Sciences,Beijing 100020,China)
  • Received:2013-10-11 Online:2014-03-28 Published:2014-03-28

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、10  μmol•L-1Aβ25-35组(Aβ组)、2%异氟醚组(Iso组)和2%异氟醚联合10  μmol•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。

关键词: 异氟醚, 阿尔茨海默病, PC12细胞, 内质网应激, 细胞凋亡

Abstract:

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,10  μmol•L-1 Aβ25-35 group (Aβ group),2% isoflurane group (Iso group),and 2% isoflurane combined with  10  μmol•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 Aβ 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 Aβ group,the  survival rate of the  PC12 cells  in Iso+Aβ 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).Conclusion 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.

Key words: isoflurane, Alzheimer&rsquo, s disease, PC12 cells, endoplasmic reticulum stress, apoptosis

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