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全反式维甲酸对环孢素诱导的肾小球系膜细胞增殖与凋亡的影响及其机制 预览

Effect and mechanism of all-trans retinoic acid on cyclosporin-induced proliferation and apoptosis of glomerular mesangial cells
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摘要 目的探讨全反式维甲酸(ATRA)对环孢素(Cs A)诱导的大鼠肾小球系膜细胞增殖及凋亡的影响及机制。方法采用不同剂量ATRA作用于不同剂量Cs A诱导下的肾小球系膜细胞。采用MTT比色法检测细胞增殖,Hoechst 33258荧光染色观察细胞凋亡形态,后用流式细胞仪检测细胞凋亡率,免疫荧光法检测线粒体促凋亡的Smac蛋白的表达。结果与对照组比较,Cs A剂量为0.5μg/m L及以上可抑制细胞増殖,Cs A剂量为1.0μg/m L及以上可诱导细胞凋亡,且Smac蛋白的表达随Cs A剂量的增加而增加,具有剂量和时间依赖的特征(均为P〈0.05)。而与Cs A组比较,Cs A+ATRA处理组对细胞增殖的抑制作用更为明显,而加入ATRA可呈剂量依赖性抑制Cs A诱导的肾小球系膜细胞凋亡及Smac蛋白的表达(均为P〈0.05)。结论 Cs A可抑制肾小球系膜细胞增殖,诱导其凋亡并刺激Smac蛋白的表达。ATRA可以抑制Cs A诱导的肾小球系膜细胞凋亡,且可能是通过Smac信号通路介导的。 Objective To investigate the effect and mechanism of all-trans retinoic acid(ATRA) on the cyclosporin(Cs A)-induced proliferation and apoptosis of glomerular mesangial cells in rat models. Methods The glomerular mesangial cells induced by different doses of Cs A were treated with different doses of ATRA. MTT assay was carried out to detect cell proliferation. Hoechst 33258 fluorescent staining was adopted to observe the morphology of the apoptotic cells. Flow cytometry was conducted to detect the cellular apoptosis rate. Immunofluorescent staining was employed to quantitatively measure the expression level of mitochondria-derived pro-apoptotic Smac protein. Results Compared with the control group, administration of Cs A at a dose of 0.5 μg/m L and above could suppress cellular proliferation, and use of Cs A at a dose of 1.0 μg/m L and above could induce cellular apoptosis. The expression level of Smac protein was significantly up-regulated by Cs A administration with a dose and time dependence(all P〈0.05).Compared with the Cs A group, combined administration of Cs A and ATRA exerted a more significant inhibitory effect on cellular proliferation. Supplement of ATRA could significantly inhibit glomerular mesangial cellular apoptosis induced by Cs A and down-regulate the expression of Smac protein with a dose dependence(both P〈0.05). Conclusions Cs A can inhibit cellular proliferation, induce cellular apoptosis and up-regulate the expression of Smac protein of glomerular mesangial cells. ATRA is capable of suppressing glomerular mesangial cellular apoptosis induced by Cs A, which is probably mediated by the Smac signaling pathway.
作者 陈旭 吴建华 郭乃凤 范亚平 陈晓岚 Chen Xu, Wu Jianhua, Guo Naifeng, Fan Yaping, Chen Xiaolan(Department of Nephrology, the Affiliated Hospital of Nantong University, Nantong 226001, China)
出处 《器官移植》 CAS CSCD 2017年第6期465-471,共7页 ORGAN TRANSPLANTATION
基金 江苏省自然科学基金(BK2008185) 南通市科技项目(MS32015018)
关键词 全反式维甲酸(ATRA) 环孢素(Cs A) 系膜细胞 肾小球 SMAC蛋白 排斥反应 细胞增殖 凋亡 肾毒性 All-trans retinoic acid(ATRA) Cyclosporin(Cs A) Mesangial cell glomerulus Smac protein Rejection reaction Cell proliferation Apoptosis Renal toxicity
作者简介 通讯作者:陈晓岚,Email:chenxl8448@sina.com
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