白细胞介素18对促进肾小管萎缩和间质纤维化的影响

Interleukin-18 Accelerates Renal Tubular Atrophy and Interstitial Fibrosis

目的 :探讨白细胞介素 18(IL - 18)对肾小管萎缩和间质纤维化的作用。方法 :在体外实验中应用不同浓度的IL - 18处理人类近端肾小管上皮细胞株 (HK - 2 )。应用Hoechst 332 5 8染色法检测细胞凋亡 ;应用流式细胞技术和免疫组化技术检测细胞表达α -平滑肌肌动蛋白 (α -SMA)表达和细胞形态学的变化。结果 :低浓度短时间IL - 18作用对细胞凋亡无影响 ,而较高浓度IL - 18作用可促使肾小管上皮细胞凋亡 ;IL - 18具有显著促进肾小管上皮细胞表达α -SMA作用 ,并呈剂量和时间依赖关系 ,而且表达α -SMA的细胞具有肌成纤维细胞的形态学特征。结论 :肾病状态下IL -

Objective:To study the effects of interleukin-18(IL-18) in tubular epithelial apoptosis and transdifferentiation for further investigation of the pathogenesis of tubulointerstitial fibrosis.Methods:Cultured human proximal tubular epithelial cells line(HK-2) were treated with recombinant human IL-18 at different concentration and for different duration. Cells apoptosis was detected by Hoechst 33258 staining. Expression of α-smooth muscle actin(α-SMA) in HK-2 cells was measured by flow cytometry and immunohistochemistry.Results:The rate of cell apoptosis significantly increased at high concentration of IL-18 but did not change at low concentration of IL-18.The rate of tubular epithelial cells expressing α-SMA significantly increased on IL-18 treatment.α-SMA expression in tubular epithelial cells was related to IL-18 in a dose- and time-dependent manner.Furthermore,features of myofibroblasts were found in epithelial cells expressing α-SMA via morphologic observation.Conclusion:IL-18 may accelerate tubular apoptosis and interstitial fibrosis in kidney disease.