p38丝裂原活化蛋白激酶在大鼠肾小管上皮细胞转分化中的作用及大黄素的干预研究

目的探讨p38丝裂原活化蛋白激酶(p38MAPK)在IL-1β诱导大鼠肾小管上皮细胞-肌成纤维细胞转分化中的作用及大黄素的干预效应。方法将体外培养的正常大鼠肾小管上皮细胞株(NRK52E)分为对照组、IL-1β诱导组、IL-1β+SB 203580组和IL-1β+大黄素组。培养48 h后用倒置相差显微镜观察细胞形态,细胞免疫化学染色检测α-平滑肌肌动蛋白(α-SMA)、角蛋白(CK)、p38MAPK及磷酸化-p38MAPK(p-p38MAPK)的表达情况。结果IL-1β可诱导部分NRK52E由卵圆形转变为梭形,同时CK表达减弱,α-SMA、p38MAPK及p-p38MAPK的表达增强。SB 203580阻断p38MAPK通路后可显著抑制IL-1β诱导的细胞形态改变,同时上调CK表达,下调α-SMA及p-p38MAPK的表达。大黄素对IL-1β诱导的细胞形态改变及α-SMA、p38MAPK及p-p38MAPK的表达也有明显抑制作用,其抑制作用与SB 203580的阻断作用相比无显著性差异。结论p38MAPK参与介导IL-1β诱导大鼠肾小管上皮细胞-肌成纤维细胞转分化过程,大黄素可通过干扰p38MAPK信号通路抑制大鼠肾小管上皮细胞转分化。

Role of p38 mitogen-activated protein kinase on tubular epithelial-myofibroblast transdifferentiationin rats and the intervention of Emodin

Objective It is to explore the role of p38 mitogenactivated protein kinase(p38MAPK) on the IL-1β-induced tubular epithelial-myofibroblast transdifferentiation(TEMT) and to explore intervention of Emodin(EMD).Methods The cultured NRK52E cells in vitro were divided into control group,IL-1β-induced group,IL-1β+SB203580 group and IL-1β+EMD group.After the cells had been cultured for 48 hours,the morphology of cells was observed under the inverted phase-contrast microscope and the expressions of α-SMA,CK,p38MAPK and p-p38MAPK were measured by immuno-cytochemistry method.Results IL-1β could induce some NRK52E became fibroblast-like-shaped and the expressions of CK decreased significantly,but α-SMA p38MAPK and p-p38MAPK increased respectively.After p38MAPK been blocked by SB 203580,the changes of morphology induced by IL-1β were inhibited,and the expressions of α-SMA and p-p38MAPK decreased respectively,CK increased significantly.EMD could significantly inhibit the morphologic changes and the expressions of α-SMA p38MAPK and p-p38MAPK.The inhibitory effects of EMD were similar to that of SB 203580.Conclusion p38MAPK takes a part in the process of TMET induced by IL-1β.EMD can inhibit the process of TMET through interventing the p38MAPK signaling pathway.