CAJ | 학술논문

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。
목적：관찰필격렬동（PIO）대고당（HG）배양적신소구계막세포（MCs）p38사렬원활화단백격매（p38MAPK）화전화생장인자β-1（TGF-β1）표체적영향，탐토PIO신보호작용급궤제。방법체외배양MCs，취대수생장기적세포이2×105/공적밀도접충우6공세포배양판，동보화후수궤분위정상대조（NG）조、HG조、p38MAPK억제제（S）조급 PIO（P）조。Western blot 측정린산화 p38MAPK（p-p38）화총 p38MAPK （t-p38）단백함량，반정량RT-PCR측정세포TGF-β1 mRNA표체정황。결과여NG조비교，HG조세포내p-p38MAPK함량화TGF-β1mRNA표체증강（P＜0．01）；여HG조비교，p38MAPK억제제현저억제HG자격적세포내p38MAPK활성화 TGF-β1표체（P＜0．05）；여 HG조비교，P 조세포내상술변화역명현강저（P＜0．05），여S조상사；p38MAPK활성화TGF-β1표체정정상관（r＝0．587，P＜0．01）。결론 PIO가억제신소구계막p38MAPK통로，강저TGF-β1표체，해작용가능여기신장보호부분유관。
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.