解剖学报

›› 2012, Vol. 43 ›› Issue (6): 784-788.doi: 10.3969/j.issn.0529-1356.2012.06.012

• 细胞和分子生物学 • 上一篇    下一篇

4-苯基丁酸抗内质网应激诱导胰岛β细胞凋亡

孙琦1* ; 向若兰2; 张文龙1; 杨燕丽3;李娟1;张葵1;丁文一1   

  1. 1.中国医学科学院北京协和医学院 北京协和医院内分泌科 卫生部内分泌重点实验室，北京 100730; 2.北京大学医学部生理与病理生理学系 分子心血管学教育部重点实验室，北京100191; 3.中国医学科学院北京协和医学院 北京协和医院内科，北京 100730
  • 收稿日期:2012-03-12 修回日期:2012-05-28 出版日期:2012-12-06
  • 通讯作者: 孙琦

Effects of 4-phenylbutyric acid on apoptosis of β cells induced by endoplasmic reticulum stress

  1. 1. Department of Endocrinology, Key Laboratory of Endocrinology Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China;2.Department of Physiology and Pathophysiology, Key Laboratory of Molecular Cardiovascular Sciences, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China;3. Department of Internal Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100730, China
  • Received:2012-03-12 Revised:2012-05-28 Online:2012-12-06
  • Contact: SUN Qi

摘要： 目的 探讨4-苯基丁酸（4-PBA）对2型糖尿病（T2DM）大鼠胰岛β细胞内质网应激（ERS）诱导的细胞凋亡的保护作用。方法 高脂饮食喂养加小剂量链脲佐菌素（STZ）腹腔注射建立SD大鼠T2DM模型，造模成功后取其中10只给予4-PBA灌胃20d。放射免疫法检测各组大鼠游离脂肪酸（FFA）、血糖及胰岛素的变化。醛品红染色观察胰岛形态改变，RT-PCR检测内质网相关蛋白（Caspase-3、GRP78、CHOP）的mRNA表达变化。结果 高脂对照组（EM> n/EM>＝10）和T2DM组（ EM>n/EM>＝8）大鼠血清FFA比正常对照组（EM>n/EM>＝10）显著增加，4-PBA治疗后显著下降（ EM>n/EM>＝8）。4-PBA治疗升高了T2DM造成的

关键词: 2型糖尿病, 内质网应激, 4-苯基丁酸, 放射免疫法, 醛品红染色, 反转录-聚合酶链反应, 大鼠

Abstract: Objective To evaluate the therapeutic effect of 4-phenylbutyric acid(4-PBA) on endoplasmic reticulum stress of type 2 diabetic (T2DM) rats. Methods To establish a T2DM model in SD rats with injection of low doses streptozotocin(STZ) after being fed with high-fat diets. Ten T2DM rats were treated with 4-PBA for 20 days. The free fatty acids(FFA), insulin and blood glucose were observed by the radioimmunological method.The pathological changes of pancreatic islet were detected by aldehyde fuchsin staining. The level of mRNA of the endoplasmic reticulum stress associated molecules (Caspase-3, GRP78, CHOP) was tested by RT-PCR. Results The concentration of FFA increased significantly in T2DM group ( EM>n/EM>＝8)and high-fat diets group( n＝10) compared with control group( EM>n/EM>＝10). 4-PBA significantly suppressed FFA caused by high-fat diets( EM>n/EM>＝8). The use of the 4-PBA prevented the decrease of insulin in T2DM group and prevented the increase of blood glucose in T2DM group. Aldehyde fuchsin staining showed that, in the T2DM group, the number of pancreatic islet decreased, the shape of pancreatic islet became unreagular, and vacuoles appeared in cytoplasma. The number of pancreatic islet increased after treatment of 4-PBA. The expression of Caspase-3 and CHOP mRNA in T2DM group significantly increased with those in control group and high-fat diets group. Enhanced expression of Caspase-3 and CHOP was decreased by 4-PBA. Conclusion Our data suggest that chemical chaperone 4-PBA may prevent the development of T2DM associated with the decreased expression of the CH

Key words: T2DM, Endoplasmic reticulum stress, 4-phenylbutyric acid, Radioimmunological method, Aldehyde fuchsin staining, RT-PCR, Rat

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