氯沙坦通过ERK1/2 MAPK途径抑制高糖诱导小鼠系膜细胞CTGF表达  

Losartan inhibits high glucose-induced CTGF expression via ERK1/2 MAPK pathways in mouse mesangial cells

作　　者：王菱[1] 陶立坚[1] 彭张哲[1] 宁旺斌[1] 

机构地区：[1]中南大学湘雅医院肾内科,湖南长沙410008

出　　处：《细胞与分子免疫学杂志》2009年第6期486-489,共4页Chinese Journal of Cellular and Molecular Immunology

基　　金：湖南省自然科学基金(07-JJ3056);教育部科学技术研究重点项目(107133);教育部博士点基金(20060533056)

摘　　要：目的:研究高糖环境下,氯沙坦对CTGF的影响以及其作用机制。方法:体外培养小鼠系膜细胞株(MMCs),用高糖(25mmol/L葡萄糖)刺激细胞分别作用24h、48h、72h,用Western blot方法检测磷酸化ERK1/2的表达。再将细胞分为低糖组(5.6mmol/L葡萄糖),山梨醇组(5.6mmol/L葡萄糖+19.4mmol/L山梨醇),高糖组(25mmol/L葡萄糖),氯沙坦组(25mmol/L葡萄糖+10-5mol/L氯沙坦)以及ERK抑制剂组(25mmol/L葡萄糖+25μmol/LPD98059),48h后采用Western blot方法检测磷酸化ERK1/2的表达,72h后采用Real-timePCR方法及Westernblot分别检测CTGFmRNA表达量以及蛋白的表达。结果:高糖刺激小鼠系膜细胞后,ERK1/2磷酸化的蛋白表达逐渐增高,呈现一定时间依赖性。与低糖组相比,高糖组磷酸化ERK1/2、CTGF的蛋白表达明显增加(P<0.01),而与高糖组相比,氯沙坦组以及ERK抑制剂组磷酸化ERK1/2的蛋白表达以及CTGF的蛋白均明显下降有统计学意义(P<0.05)。与低糖组相比,高糖组CTGF mRNA表达量明显增加(P<0.01),而与高糖组相比,氯沙坦组以及ERK抑制剂组CTGF mRNA表达量明显下降,且有统计学意义(P<0.01)。结论:氯沙坦可抑制高糖对CTGF的诱导作用,其机制可能与抑制ERK1/2MAPK途径有关。AIM：To investigate the effects and mechanism of losartan on expression of CTGF induced by high glucose. METHODS：Mouse mesangial cells （MMCs） were cultured in vitro,initially,MMCs were stimulated by high glucose（25 mmol/L glucose） for 24 h,48 h,72 h,the phosphorylation of ERK1/2 was assessed by Western blot. Then MMCs were randomly divided into 5 groups：（1） Low glucose group （5.6 mmol/L glucose）; （2）Sorbitol group （5.6 mmol/L glucose＋19.4 mmol/L sorbitol）; （3） High glucose group （25 mmol/L glucose）; （4） Losartan group （25 mmol/L glucose＋ 10^5 mol/L losartan）; （5） ERK inhibitors group （25 mmol/L glucose＋25 μmol/L PD98059）. After 48 hours,the phosphorylation of ERK1/2 were detected by Western blot. After 72 hours,the protein and mRNA expression level of CTGF were assessed by Western blot and real-time PCR. RESULTS：High glucose induced the phosphorylation of ERK1/2 in a time-dependent manner. The protein expression of phosphor-ERK1/2 and CTGF were increased in high glucose group comparing with low glucose group（P〈0.01）,and reduced in losartan group and ERK inhibitors group comparing with high glucose group（P〈0.05）. The mRNA expression of CTGF was increased in high glucose group comparing with low glucose group（P〈0.01） ,and reduced in losartan group and ERK inhibitors group comparing with high glucose group（P〈0.01）. CONCLUSION：Losartan can inhibit high glucose-induced CTGF expression in mouse mesangial cells,and the mechanisms maybe involve the interruption of ERK1/2 MAPK pathway.

关 键 词：氯沙坦 高糖 CTGF ERK1/2 系膜细胞 

分 类 号：R322.61[医药卫生—人体解剖和组织胚胎学]