不同浓度尿酸对大鼠肾小球内皮细胞增殖、NO合成及ET-1分泌的影响

Effects of Uric Acid on the Production of Nitric Oxide、Endothelin-1 and the Proliferation of Rats Glomerular Endothelial Cell in Vitro

目的:通过体外细胞培养,观察不同浓度尿酸(UA)抑制肾小球内皮细胞(glomerular endothelial cells,GECs)增殖及对一氧化氮(NO)、内皮素1(ET-1)分泌的影响。方法:取大鼠肾小球内皮细胞(GECs)进行实验,用MTT比色法观察不同浓度UA(0、2、4、8、16mg/dl)作用48 h对GECs增殖的影响。用ELISA方法评价不同浓度UA(0、2、4、8、16mg/dl)作用48 h对GECs培养液中NO、ET-1浓度的影响。结果:UA呈剂量依赖性抑制GECs增殖,浓度为8、16 mg/dl的UA组与对照组(0 mg/dl UA)比较差异均有统计学意义(P<0.05)。UA呈浓度依赖性抑制GECs合成NO,各组UA与对照组比较差异均有统计学差异(P<0.05);尿酸呈浓度依赖性刺激GECs分泌ET-1,其中8 mg/dl和16 mg/dl尿酸浓度组于对照组(0 mg/dl)比较差异有统计学意义(P<0.05)。结论:尿酸可抑制内皮细胞增殖,并引起NO合成减少及ET-1分泌增加,尤其高于生理浓度的尿酸刺激组(≥8 mg/dl)上述作用更加明显,可能是尿酸导致内皮细胞功能障碍的机制。

Objective：To investigate the effects of uric acid（UA）on the production of nitric oxide（NO）、endothelin-1（ET-1）and the proliferation of cultured rats glomerular endothelial cells（GECs）.Methods：The effects of UA（0、2、4、8、6 mg/dl）on the proliferation of GECs were observed after 48 hours by MTT assay.GECs were incubated with different concentration（0、2、4、8、16 mg/dl）of UA for 48 hours.NO and ET-1 in supernatant medium were detected by cell ELISA.Results：UA inhibited the proliferation of GECs in a dose-dependent manner,compared with control group（0 mg/dl UA）,UA（8,16 mg/dl）group could inhibit the proliferation of GECs（P0.01）.NO inhibited by UA in GECs remarkably decreased in a dose-dependent manner.ET-1 activated by UA in GECs remarkably increased in a dose-dependent manner,compared with control group,UA（8,16 mg/dl）group could enhance the production of ET-1 in GECs（P0.01）.Conclusion：UA could obviously inhibit the proliferation of GECs and the production of NO and stimulate the production of ET-1 in GECs,especially,in uric acid group which higher than physical concentration.These may thereby play an important role in the dysfunction of the endothelial cells.