中国药理学通报2018，Vol.34Issue(1)：112-117,6.DOI:10.3969/j.issn.1001-1978.2018.01.024
过表达THEM4对糖尿病小鼠肾脏细胞外基质沉积的影响
Role of up-regulation of THEM4 on extracellular matrix accumulation in kidney of diabetic mice
摘要
Abstract
Aim To observe the effect of thioesterase superfamily member 4 ( THEM4 ) expression on extra-cellular matrix ( ECM ) accumulation in the kidney of diabetic mice .Methods For in vivo vector delivery experiment , male CD1 mice were randomly divided in-to four groups: normal control mice ( Control group ) , diabetic mice ( DM group ) , diabetic mice receiving pYr-ads-4-THEM4 vector ( DM+THEM4 vector ) and diabetic mice receiving pYr-adshuttle-4 vector ( DM+V vector ) .pYr-ads-4-THEM4 vector or pYr-adshuttle-4 vector ( 1 mg · kg -1 ) were mixed with TransIT-EE Hydrodynamic Delivery Solution from Mirus Co .and injected into tail vein once a week for four weeks after STZ injection.Four weeks later, mice were sacrificed and Western blot , immunohistochemistry and real-time PCR were used to detect the expression of phospho-Akt(Ser 473), THEM4, TGF-β1, α-SMA, Col Ⅲ, FN proteins and THEM4 mRNA in kidneys respectively . Results THEM4 decreased in kidney of diabetes mel-litus accompanied with increased phospho-Akt ( Ser 473), TGF-β1, α-SMA and ECM.The delivery of pYr-ads-4-THEM4 vector increased THEM4 expression and decreased phospho-Akt (Ser 473), TGF-β1, α-SMA and ECM deposit in kidneys of diabetic mice . Conclusion The up-regulation of THEM4 may pre-vent ECM deposit by inhibiting the phosphorylation of Akt and down-regulating the expression of TGF-β1 andα-SMA in kidneys of diabetic mice .关键词
硫酯酶超家族成员4/PI3K/Akt/糖尿病小鼠/细胞外基质/转化生长因子β1/纤维黏连蛋白Key words
thioesterase superfamily member 4/PI3K/Akt/diabetic mice/extracellular matrix/TGF-β1/fibronectin分类
医药卫生引用本文复制引用
陈宁,郝军,朱桂云,安晓颖,孙精晶,欧阳琴,杨永辉..过表达THEM4对糖尿病小鼠肾脏细胞外基质沉积的影响[J].中国药理学通报,2018,34(1):112-117,6.基金项目
河北省医学科学研究重点课题计划(No20150604) （No20150604）
