中文摘要：

目的探讨前列腺素E2（PGE2）受体1亚型（EP1）拮抗剂（SC-19220）对转化生长因子（TGF）B1诱导的小鼠肾小球系膜细胞增殖、前列腺素合酶表达、细胞外调节蛋白激酶（ERK）信号通路的影响及可能机制。方法小鼠肾小球系膜细胞分组：对照组；TGF-β1（10μg/L）组；药物干预组：不同浓度（0．1、0．5、1.0μmol／L）SC-19220＋TGF-β1（10μg／L）组。CCK-8法检测细胞增殖；ELISA法检测细胞上清中PGE2的表达；实时荧光定量PCR法检测细胞结缔组织生长因子（CTGF）、层粘连蛋白（LN）、环氧化酶2（COX2）、膜结合型前列腺素E2合酶1（mPGESl）mRNA的表达。Western印迹法检测CTGF、LN、COX2、mPGESl及ERKl／2活性变化。结果与对照组比，TGF．131组系膜细胞增殖增加（P＜0．05），PGE：表达增加（P＜0．05），CTGF、LN、COX2、mPGESlmRNA及蛋白表达增加（P＜0．05），ERKl／2活性增加（P＜0．05）。SC-19220干预后呈剂量依赖性抑制系膜细胞增殖（P＜O．05），下调PGE2的表达（P＜0．05），抑制CTGF、LN、COX2、mPGESlmRNA及蛋白表达（P＜0．05），抑制ERKl／2活性（P＜0．05）。结论SC-19220可能通过抑制ERKl／2活性，反馈抑制COX2、mPGESl及PGE2的表达，从而下调CTGF、LN的表达，减轻TGF-131诱导的系膜细胞损伤。

英文摘要：

Objective To explore the effects and mechanisms of prostaglandin E2 （PGE2） receptor 1 antagonist （SC-19220） on proliferation, prostaglandin synthase and extracellular regulated protein kinases （ERK） signal pathway induced by transforming growth factor 131（TGF-βl） in glomerular mesangial cells. Methods Mouse glomerular mesangial cells （GMCs） were divided into 5 groups： control group, TGF-[31 （10μg/L） group, TGF-131 （10μg/L） plus SC-19220 group （0.1, 0.5, 1.0μmol/L）. The proliferation of GMCs was measured by CCK-8. The PGE2 in supernatant was measured by ELISA. The expression of connective tissue growth factor （CTGF）, laminin （LN）, cyclooxygenase 2（COX2）, membrane-bound prostaglandin E2 synthase 1 （mPGES1） protein and mRNA was examined by Western blotting and real-time quantitative PCR, ERK1/2 or phospho-ERK1/2 was measured by Western blotting as well. Results TGF-β1 induced the proliferation of GMCs and increased the secretion ofPGE2. Besides, TGF-131 significantly up-regulated the expression of CTGF, LN, COX2 and mPGES1 mRNA and protein （P〈 0.05）, and increased the expression of phospho-ERK1/2 protein （P 〈 0.05）. However, SC- 19220 significantly attenuated the changes of above- mentioned parameters and their activities （P〈 0.05）. All the effects of SC- 19220 were in dose-dependent manner. Conclusions SC- 19220 may reduce TGF-131- induced cell damage by suppressing the activity of ERK1/2, and feedback inhibition of COX2, mPGES1 and PGE2, thus decreases the expression of LN and CTGF.