【摘要】 目的研究丹参酮Ⅱ-A磺酸钠(sodium tanshinoneⅡ-A sulfonate,DS-201)对人肾间质纤维化来源的成纤维细胞(human renal interstitial fibroblasts,hRIFs)体外增殖及细胞周期素E(cyclin E)基因表达的影响,探讨该药治疗肾间质纤维化的作用机制。方法体外培养并鉴定hRIFs;用四甲基偶氮唑(MTT)法检测对照组与不同DS-201浓度组hRIFs的增殖活性;用免疫细胞化学S-P法和图像分析技术检测对照组与不同DS-201浓度组hRIFs cyclin E基因的表达。结果随药物浓度的升高和作用时间的延长,抑制率逐渐升高,抑制作用逐渐增强,呈剂量依赖性和时间依赖性。用药组阳性细胞的平均光密度值在第3、5、7、9天显著低于对照组(P<0.05,P<0.01),第1天用药各组与对照组之间无统计学差异(P>0.05)。结论①DS-201对hRIFs体外增殖有显著抑制作用,可能是其治疗肾间质纤维化的机制之一。②DS-201抑制hRIFs体外增殖可能是通过抑制细胞中cyclin E基因的表达,阻滞细胞通过G1/S关卡,延长细胞周期实现的。更多还原

【Abstract】 Objective To study the effect of sodium tanshinone Ⅱ-A sulfonate (DS-201)on the proliferation of human renal interstitial fibroblasts (hRIFs) and the expression of cyclin E. Methods After hRIFs were cultured and identified, MTT was used to detect the cells at passage 3-4 in present or absent of DS-201at different concentrations. The expression of cyclin E was analyzed by immunocytochemistry and the image-analytical technique. Results With the increase of the drug concentration and prolongation of action time, the inhibitory ratio was increased in a dose- and time-dependent manner. The expression of cyclin E was stronger in drug groups than in control group on the 3rd, 5th, 7th and 9th day (P<0.05,P<0.01). Conclusion DS-201 significantly inhibits the hRIFs in vitro,which may be one of its mechanisms to suppress renal interstitial fibrosis. The mechanism of this inhibition may be due to that sodium tanshinone Ⅱ-A sulfonate inhibits the expression of cyclin E, thus blocks the G1/S point and extents the cell cycle.更多还原