目的观察过表达硫酯酶超家族成员4（thioesterase superfamily member 4,THEM4）对高糖诱导的人肾小管上皮细胞胶原分泌的影响。方法体外培养人肾小管上皮细胞（human rena"/>
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过表达THEM4对高糖诱导的人肾小管上皮细胞胶原分泌的影响

Ning CHEN,Jun HAO,Gui-yun ZHU,Xiao-ying AN,Li-fei KANG,Xiao-xia LI,Yong-hui YANG

Chinese Pharmacological Bulletin（2017）

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Abstract
目的观察过表达硫酯酶超家族成员4（thioesterase superfamily member 4,THEM4）对高糖诱导的人肾小管上皮细胞胶原分泌的影响。方法体外培养人肾小管上皮细胞（human renal proximal tubular epithelial cell,HKC）,将细胞随机分为正常对照组(5.5 mmol·L-1normal glucose,Control)、高糖组(30 mmol·L-1high glucose,HG)、高糖+p Yrads-4-THEM4质粒转染组（HG+THEM4）、高糖+p Yr-adshuttle-4空质粒对照组（HG+V）。后3组经高糖刺激48 h后终止培养,Western blot检测THEM4、phospho-Akt（Ser473）、TGF-β1、α-SMA的表达;免疫细胞荧光检测THEM4蛋白表达和定位;ELISA方法检测细胞上清液中Ⅰ型胶原（collagenⅠ,ColⅠ）、Ⅲ型胶原（collagenⅢ,ColⅢ）分泌情况。结果高糖刺激可导致人肾小管上皮细胞内THEM4表达降低,phospho-Akt（Ser 473）、TGF-β1、α-SMA的表达增强及ColⅠ、ColⅢ分泌;过表达THEM4能够逆转高糖刺激所导致人肾小管上皮细胞phospho-Akt（Ser 473）蛋白的活化,下调α-SMA、TGF-β1表达,抑制ColⅠ、ColⅢ的分泌。结论过表达THEM4能够降低高糖诱导的胶原分泌,可能是通过抑制phospho-Akt（Ser 473）蛋白的活化,下调α-SMA、TGF-β1表达而实现的。
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Key words
thioesterase superfamily member 4,PI3K/ Akt,high glucose,human renal tubular cells,TGF-β1,collagen Ⅰ,collagen Ⅲ
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