间歇低氧对大鼠INS-1细胞JNK、PDX-1的影响  

Effect of Intermittent Hypoxia on JNK and PDX-1 of INS-1 Pancreatic Beta Cells in Rats

作　　者：卢巍[1,2] 于娜[1] 林雪娇[1] 王东亮 康健[1] 

机构地区：[1]中国医科大学附属第一医院呼吸内科,沈阳110001 [2]解放军202医院呼吸内科,沈阳110003

出　　处：《解放军医药杂志》2014年第7期56-60,共5页Medical & Pharmaceutical Journal of Chinese People’s Liberation Army

摘　　要：目的体外培养大鼠INS-1细胞,观察间歇低氧条件直接作用于细胞引起的改变。方法常氧组细胞(CON)不进行间歇低氧暴露,IH组细胞暴露间歇低氧,收集暴露(1、2、3 d)的培养上清及细胞,检测氧化应激指标超氧化物歧化酶(SOD)、丙二醛(MDA)及JNK1 mRNA、JNK1/2蛋白表达水平。给予SP600125阻断JNK蛋白活性,观察下游基因PDX-1 mRNA及蛋白变化。结果随着间歇低氧暴露时间的延长,IH组细胞培养上清中MDA含量呈增高趋势,SOD活力呈降低趋势。IH组细胞表达JNK1 mRNA较相应时间CON组明显增高,其表达量进行性下降。磷酸化JNK1于IH 3 d组呈现出高表达。给予SP600125可引起PDX-1蛋白明显增高。结论间歇低氧可以直接引起INS-1细胞氧化损伤,随暴露时间的延长而加重,可能是通过诱导JNK1转录水平及蛋白活化而实现的。Objective To observe the direct effect on INS-1 cells of rats cultured in vitro under intermittent hy-poxia. Methods Cells in common oxygen group （CON group） was not exposed under intermittent hypoxia, while cells in intermittent hypoxia group （IH group） were exposed under intermittent hypoxia. Cultured supernate and cells were col-lected at 1st d, 2nd d and 3rd d after exposure and the levels of superoxide dismutase （SOD）, malondialdehyde （MDA） and expressions of JNK1 mRNA and JNK1 / 2 in the two groups were detected. SP600125 was used to bolck the activity of JNK, and changes of downstream gene PDX-1 mRNA and protein were also observed. Results The MDA level at super-nate was significantly higher and SOD activity was significantly decreased in cultured supernate of IH group with prolonged exposure time under intermittent hypoxia. JNK1 mRNA expression was significantly upregulated in IH group compared with that in CON group at the same time, and expression value was progressively decreased. The high phospho-JNK1 ex-pression was found 3th d after exposure. The expression of PDX-1 was significantly increased after using SP600125. Con-clusion Intermittent hypoxia may directly induce oxidative damage effect on INS-1 cells, and the damage becomes seri-ous with time prolonging, and its damage may be done by inducing transcriptional level and protein activation.

关 键 词：细胞低氧 氧化性应激 胰岛素分泌细胞 大鼠 

分 类 号：R332[医药卫生—人体生理学]