吡格列酮对高糖培养大鼠肾小球系膜细胞p38丝裂原活化蛋白激酶和转化生长因子β-1的影响  

Effects of pioglitazone on the expressions of p38 mitogen-activated protein kinase and transforming growth factor β-1 in cultured rat glomerular mesangial cells

作　　者：汪姗[1] 叶山东[1] 孙文佳[1] 胡圆圆[1] 

机构地区：[1]安徽医科大学附属省立医院,安徽省立医院内分泌科,合肥230001

出　　处：《中国临床保健杂志》2014年第2期160-162,I0002,共4页Chinese Journal of Clinical Healthcare

基　　金：安徽省自然科学基金(11040606M161);安徽高校省级自然科学研究项目(KJ2011A157)

摘　　要：目的观察吡格列酮(PIO)对高糖(HG)培养的肾小球系膜细胞(MCs)p38丝裂原活化蛋白激酶(p38MAPK)和转化生长因子β-1(TGF-β1)表达的影响,探讨PIO肾保护作用及机制。方法体外培养MCs,取对数生长期的细胞以2×105/孔的密度接种于6孔细胞培养板,同步化后随机分为正常对照(NG)组、HG组、p38MAPK抑制剂(S)组及PIO(P)组。Western blot测定磷酸化p38MAPK(p-p38)和总p38MAPK(t-p38)蛋白含量,半定量RT-PCR测定细胞TGF-β1 mRNA表达情况。结果与NG组比较,HG组细胞内p-p38MAPK含量和TGF-β1mRNA表达增强(P<0.01);与HG组比较,p38MAPK抑制剂显著抑制HG刺激的细胞内p38MAPK活性和TGF-β1表达(P<0.05);与HG组比较,P组细胞内上述变化亦明显降低(P<0.05),与S组相似;p38MAPK活性和TGF-β1表达呈正相关(r=0.587,P<0.01)。结论 PIO可抑制肾小球系膜p38MAPK通路,降低TGF-β1表达,该作用可能与其肾脏保护部分有关。Objective To observe the effects of pioglitazone on the expressions of p38 mitogen-activated pro-tein kinase （p38MAPK）and transforming growth factor β-1 （TGF-β1 ）in cultured rat glomerular mesangial cells （MCs）and explore its reno-protective mechanism.Methods MCs were cultured in the medium with normal glucose concentration （group NG）,high glucose concentration （group HG）,p38MAPK special inhibitor（group S）and piogli-tazone （group P）.The expression levels of phosphory1ated p38MAPK （p-p38）and total p38MAPK （t-p38）were measured by Western blot.The expressions of TGF-β1 mRNA were detected by semiquantitative RT-PCR.Results Compared with group NG,the p38MAPK activity and TGF-β1 mRNA expression increased significantly （P〈0.01）in group HG.Compared with group HG,p38MAPK special inhibitor inhibited markly HG-induced p38MAPK activity and TGF-β1 expression （P〈0.05）.When treated with pioglitazone,p38MAPK activity and TGF-β1 expression decreased （P〈0.05）,which were similar to group S.p38MAPK activity was positively correlated with TGF-β1 expression （r=0.587,P〈0.01）.Conlusions Pioglitazone can suppress TGF-β1 expression of MCs via p38MAPK pathway,which may contribute partly to its reno-protection.

关 键 词：糖尿病肾病 肾小球系膜细胞 P38丝裂原活化蛋白激酶类 转化生长因子β1 噻唑烷二酮类 1 

分 类 号：R587.2[医药卫生—内分泌] R692[医药卫生—内科学]