THEM4/Akt在糖尿病小鼠肾脏细胞外基质沉积中的作用

摘要

目的 探讨硫酯酶超家族成员4(thioesterase superfamily member 4, THEM4)/Akt在糖尿病小鼠肾脏中的表达以及与细胞外基质沉积的关系.方法 采用链脲佐菌素(streptozotocin,STZ)腹腔注射复制糖尿病小鼠模型,饲养8周后处死小鼠,应用 Western blot、免疫组化及 RT-PCR技术检测糖尿病小鼠肾脏中 THEM4/Akt、phospho-Akt(Ser 473)、TGF-β1、α-SMA、Col Ⅲ、 FN蛋白及THEM4 mRNA的表达.结果 与对照组小鼠相比,糖尿病小鼠肾脏中THEM4蛋白低表达,相对于对照组下降了37.7％;同时伴随phospho-Akt(Ser 473) 、TGF-β1、α-SMA、Col Ⅲ及FN蛋白表达升高,较对照组分别上调了3.66、1.29、2.33、1.99及2.82倍;糖尿病小鼠肾小管间质可见细胞外基质沉积.结论 糖尿病小鼠肾小管间质细胞外基质沉积可能是由于 THEM4的低表达进而激活Akt,上调TGF-β1和α-SMA蛋白的表达而实现的.%Purpose To investigate the relations of THEM4/Akt expression and extracellular matrix deposit in kidney of diabetic mice. Methods Diabetic mice models were successfully established by intraperitoneally injected STZ. Both normal control mice and diabetic mice were raised for 8 week until they were sacrificed. Western blot, immunohistochemistry and realtime PCR were used to detect the expression of THEM4, phospho-Akt (Ser 473), TGF-β1, a-SMA, Col Ш, FN protein and THEM4 mRNA in the kidneys of normal mice and diabetic mice. Results Compared to normal control mice, THEM4 expression decreased by 37.7％ followed by 3.66, 1.29 2.33, 1.99 and 2.82 times increased of phospho-Akt (Ser473), TGF-β1, a-SMA, Col Ш and FN in kidney of diabetes mellitus. Extracellular matrix accumulation was found in renal interstitial region of diabetic mice. Conclusion The decreased THEM4 might cause extracellular matrix deposit in kidney of diabetic mice by upregulating the phosphorylation of Akt and TGF-β1, α-SMA expression in diabetic mice.