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目的研究芳维A酸乙酯(AE)对体外培养小鼠肾小球系膜细胞(GMC)增殖、凋亡及TGF-β1表达的影响。方法采用MTT法检测芳维A酸乙酯(AE)、全反式维A酸(atRA)对GMC增殖的影响;采用流式细胞仪检测AE干预后GMC的凋亡情况;采用ELISA法检测AE干预后GMC培养上清液中TGF-β1的含量。结果与正常组对比,AE干预组GMC增殖受到抑制(P<0.05),且当浓度在10~(-8)到10~(-5)mol/L范围内时,作用成剂量依赖性。AE能够诱导GMC的凋亡,正常组、10~(-7)mol/L、10~(-5)mol/L的AE干预组的GMC细胞凋亡率分别为(1.13±0.36)%、(9.52±0.99)%和(27.23±2.88)%。AE能够抑制GMC的TGF-β1分泌,与空白对照组,AE干预组TGF-β1表达降低(P<0.05)。AE抑制GMC增殖、诱导GMC凋亡及抑制GMC TGF-β1分泌的作用明显强于atRA。结论AE可以抑制体外GMC增殖并能诱导凋亡,其抑制增殖的作用可能与TGF-β1表达降低有关。AE可干预狼疮性肾炎病理病理进程。
Objective To study the effects of aryl retinoic acid ethyl ester (AE) on the proliferation, apoptosis and the expression of TGF-β1 in cultured mouse glomerular mesangial cells (GMCs). Methods MTT assay was used to detect the effect of aryl retinoic acid (AE) and all-trans retinoic acid (atRA) on the proliferation of GMCs. The apoptosis of GMCs was detected by flow cytometry (FCM) The content of TGF-β1 in GMC culture supernatant after intervention. Results Compared with the normal group, the proliferation of GMC was inhibited in AE group (P <0.05), and the effect was dose - dependent when the concentration was in the range of 10 -8 to 10 -5 mol / L. AE could induce the apoptosis of GMC. The apoptotic rates of GMC in normal group, (10 ± 7) mol / L and 10 -5 mol / L groups were (1.13 ± 0.36)% and 9.52 ± 0.99)% and (27.23 ± 2.88)%. AE could inhibit the secretion of TGF-β1 in GMC. Compared with the blank control group and the AE intervention group, TGF-β1 expression decreased (P <0.05). AE significantly inhibited GMC proliferation, induced GMC apoptosis and inhibited GMC TGF-β1 secretion than atRA. Conclusion AE can inhibit proliferation and induce apoptosis of GMC in vitro, which may be related to the decrease of TGF-β1 expression. AE can interfere with pathological course of lupus nephritis.