氟伐他汀对高糖腹透液诱导人腹膜间皮细胞纤连蛋白表达的影响及机制研究  

Effect and mechanism of fluvastatin on the expression of fibronectin in human peritonealmesothelial cells induced by high-glucose peritoneal dialysate

作　　者：刘艳春[1] 刘佳[1] 徐亚光[1] 赵秀芬[1] 钱军[1] 孙彬[1] 邢昌赢[1] 

机构地区：[1]南京医科大学第一附属医院肾内科,210029

出　　处：《中华肾脏病杂志》2012年第11期888-893,共6页Chinese Journal of Nephrology

摘　　要：目的探讨氟伐他汀对高糖腹透液（HGPDS）诱导人腹膜问皮细胞（HPMC）纤连蛋白（FN）表达的影响及机制研究。方法体外培养HPMC，随机分为正常对照组、HGPDS诱导组、HGPDS＋GSK650394[血清和糖皮质激素诱导的激酶1（SGK1）抑制剂，10^-5mol／L]组、不同浓度氟伐他汀组、单纯氟伐他汀（10^-6mol／L）组及GSK650394干扰组（10^-5mol/L）。倒置显微镜观察细胞形态，MTT法检测细胞活力，RT-PCR及Western印迹、ELISA法检测SGKl、FN的mRNA和蛋白表达。结果在HGPDS作用下，细胞由铺路石样转变为长梭形，细胞活力明显受抑（P〈0．05）。GSK650394及氟伐他汀（10^-6mol／L）可使细胞形态得到部分恢复，细胞活力明显改善（P〈0．05）。HGPDS明显增加HPMCSGKl、FN的mRNA及蛋白的表达，但可被GSK650394明显抑制（P〈0．05），而不同浓度氟伐他汀均具有与SGKl抑制剂的类似作用（P〈0．05），并呈浓度依赖性。结论高糖腹透液诱导体外培养人腹膜间皮细胞FN表达增加，氟伐他汀可以抑制FN表达，其机制可能与氟伐他汀抑制SGKl通路有关。Objective To explore the effect and mechanism of fluvastatin on the expression of fibroneetin（FN） in human peritoneal mesothelial ceils （HPMCs） induced by high-glucose peritoneal dialysate （HGPDS）. Methods Cultured HPMCs were randomly divided into control, HGPDS, HGPDS plus GSK650394 10^-5 mol/L （the competitive inhibitor of SGK1）, different concentrations of fluvastatin, fluvastatin 104 mol/L and GSK650394 10^-6 mol/L alone. The morphology change of HPMC was observed by light microscopy. The cellular viability was detected by MTT colorimetry. The mRNA and protein expressions of serum and glucocorticoid-inducible kinase 1 （SGK1） and FN were detected by RT- PCR, Western blotting or ELISA. Results After incubation with HGPDS, the cell morphology changed from typical cobblestone- like appearance to fibroblast- like appearance, and the cell viability was inhibited significantly （P〈0.05）. Fluvastatin 10^-6mol/L and GSK650394 could improved the cell morphology and the cell viability injured by HGPDS （P〈0.05）. Compared with tbe normal control group, the mRNA and protein expressions of SGK1 and FN increased significantly in HPMC treated with HGPDS（P〈0.05）. GSK650394 significantly decreased the high expression of SGK1and FN （P〈0.05）, also the fluvastatin had same effects as GSK650394 in dose-dependent manner （P〈 0.05）. Conclusions High- glucose peritoneal dialysate can increase FN expression in human peritoneal mesothelial cells, which can be attenuated by fluvastatin. The protective role of fluvastatin in HPMC may be partially achieved through the signal pathway of SGK1.

关 键 词：透析液 纤连蛋白类 氟伐他汀 腹膜间皮细胞 血清和糖皮质激素 诱导的激酶1 

分 类 号：R[医药卫生]