西格列汀对AGEs作用下系膜细胞自噬的影响

发布时间：2018-06-11 12:10

本文选题：西格列汀 + 自噬　；参考：《中国病理生理杂志》2017年08期

【摘要】：目的:探讨西格列汀对晚期糖基化终末产物(advanced glycation end products,AGEs)作用下系膜细胞细胞外基质和自噬相关蛋白表达的影响。方法:培养大鼠肾小球系膜细胞,共分5组,分别为正常对照(control)组、AGE组和不同浓度(5、10和20μmol/L)西格列汀组。培养48 h后采用MTT法测定细胞活力,采用ELISA法检测细胞培养上清胶原蛋白Ⅳ(collagen IV,Col IV)含量的变化。采用Western blot检测自噬相关蛋白beclin-1、腺苷酸活化蛋白激酶(adenosine monophosphate-activated protein kinase,AMPK)、p-AMPK、p70S6K和p-p70S6K的蛋白水平。结果:与control组比较,AGEs可明显引起系膜细胞活力和Col IV表达增加,不同浓度的西格列汀均可明显抑制AGEs诱导的系膜细胞活力和Col IV表达的增加;与control组比较,AGEs可引起系膜细胞自噬相关蛋白beclin-1表达和AMPK磷酸化水平下降,p70S6K磷酸化水平增加;不同浓度的西格列汀均可促进系膜细胞自噬相关蛋白beclin-1表达及AMPK磷酸化,抑制p70S6K磷酸化,并呈一定的浓度依赖性。结论:西格列汀可能通过引起系膜细胞的自噬发挥肾脏保护作用。
[Abstract]:Aim: to investigate the effect of siglitatin on the expression of extracellular matrix and autophagy related protein in Mesangial cells under the action of advanced glycation end products (ages). Methods: rat glomerular Mesangial cells were cultured and divided into 5 groups: control group (control group), age group (n = 10) and siglitatin group (n = 10 and 20 渭 mol / L). After 48 h culture, MTT assay was used to determine cell viability and Elisa was used to detect the changes of collagen IV collagen IVCol (IVCol) content in the supernatant of cell culture. The protein levels of autophagy associated protein beclin-1, adenosine monophosphate-activated protein kinase, p70S6K and p-p70S6K were detected by Western blot. Results: compared with control group, ages could significantly increase the activity of Mesangial cells and the expression of Col IV, and different concentrations of siglitatin could significantly inhibit the activity of Mesangial cells and the expression of Col IV induced by ages. Compared with control group, ages could induce the decrease of beclin-1 expression of autophagy associated protein and the increase of phosphorylation of p70S6K in Mesangial cells, and different concentrations of siglitatin could promote the expression of beclin-1 and AMPK phosphorylation of autophagy related protein in Mesangial cells. The phosphorylation of p70S6 K was inhibited in a concentration dependent manner. Conclusion: siglitatin may play a role in renal protection by inducing autophagy of Mesangial cells.
【作者单位】：暨南大学医学院附属广州红十字会医院全科医学科;
【基金】：广州市卫生和计划生育科技一般引导项目(No.20161A011020)
【分类号】：R587.2;R692.9

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