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目的研究1种牛儿基牛儿醇转移酶抑制(GGTI-286)对大鼠肾小球系膜细胞增殖的影响。方法用含有不同浓度的GGTI-286处理被10%胎牛血清(FCS)或血小板源生长因子(PDGF)刺激的大鼠肾小球系膜细胞,应用细胞增殖ELISA系统测定溴化脱氧尿嘧啶核苷进入细胞的量来评估DNA的合成,并测定细胞的数量。用蛋白质印迹法研究GGTI-286对原癌基因(Ras)蛋白和丝裂原活化蛋白激酶(MAPK)活化的影响。结果GGTI-286对10%FCS或PDGF刺激大鼠肾小球系膜细胞DNA的合成抑制是剂量依赖性,并且能够抑制细胞的生长,应用台盼蓝排除试验,GGTI-286并不改变系膜细胞的存活率。GGTI-286也能够抑制10%FCS或PDGF诱发的肾小球系膜细胞Ras蛋白活动和MAPK的激活。结论GGTI-286通过影响肾小球系膜细胞Ras蛋白活动和MAPK的激活而抑制肾小球系膜细胞增殖,这可能为治疗系膜增殖性肾小球疾病提供1种新的方法。
Objective To investigate the effects of GGTI-286 on glomerular mesangial cell proliferation in rats. Methods Rat glomerular mesangial cells stimulated with 10% fetal bovine serum (FCS) or platelet derived growth factor (PDGF) were treated with different concentrations of GGTI-286. The cell proliferation ELISA system was used to determine the levels of bromodeoxyuridine The amount of glycoside that enters the cells is used to assess DNA synthesis and determine the number of cells. The effect of GGTI-286 on the activation of protooncogene (Ras) protein and mitogen-activated protein kinase (MAPK) was studied by Western blotting. Results The inhibitory effect of GGTI-286 on the synthesis of rat glomerular mesangial cells stimulated with 10% FCS or PDGF was dose-dependent and inhibited the growth of the cells. The GGTI-286 did not change the mesangial Cell survival rate. GGTI-286 also inhibited Ras protein activity and MAPK activation induced by 10% FCS or PDGF in mesangial cells. Conclusion GGTI-286 can inhibit the proliferation of mesangial cells by affecting Ras protein activity and MAPK activation in mesangial cells, which may provide a new method for the treatment of mesangial proliferative glomerular disease.