Objective To study the effects of sodium tanshinone ⅡA sulfonate ( STS ) under normoxia and hypoxia on proliferation of keloid fibroblasts ( KFs) and expression of pro-fibrogenic factors, and to explore the potential therapeutic role of STS for keloid. Methods A total of 5 cases of KFs were cultured and then divided into different groups.The samples were treated with different doses of STS (0, 50, 100, 200, 400, and 800 μmol/L) for 48 h under normoxia (21% O2) or hypoxia (2% O2).The proliferation activity of KFs was detected with CCK-8 kit and the cell morphology was observed under inverted phase contrast microscope.After treatment of STS (0, 100, and 200μmol/L, respectively), real time PCR assay was adopted to measure the mRNA expression of hypoxia inducible factor 1α(HIF-1α), transforming growth factorβ1 (TGF-β1), collagen typeⅠ(ColⅠ), collagen typeⅢ( Col Ⅲ) , vascular endothelial growth factor ( VEGF) , and periostin ( PN) .The protein expressions of HIF-1αand TGF-β1 were examined by western blot assay. Results The proliferation activity of KFs was not significantly different between normoxia and hypoxia.The STS inhibited the proliferation of KFs in a dose-dependent manner in normoxia and hypoxia (P<0.05).The minimal effective dose in hypoxia was higher than that in normoxia.Hypoxia for 48 h changed the expressions of pro-fibrogenic factors.The mRNA and protein expressions of HIF-1αwere increased by 0.606 (P=0.037) and 0.950 (P=0.002), respectively.The mRNA expression of VEGF was increased by 7.256 (P=0.043).The mRNA expression of periostin was increased by 6.285 (P=0.006).The protein expression of TGF-β1 was increased by 1.641 (P=0.011).However, the STS did not significantly effected on the mRNA expressions of ColⅠand Col Ⅲ.Treated with STS under normoxia for 48 h, the mRNA expressions of HIF-1αand periostin were increased by 0.750 (P=0.015) and 8.553 (P=0.000), respectively.The mRNA expressions of TGF-β1, ColⅠ, and ColⅢwere decreased by 0.349 (P=0.007), 0.320 (P=0.006), and 0.453 (P=0.015), respectively.There were not significant changes in the expressions of TGF-β1 protein and VEGF mRNA (P>0.05).Treated with STS under hypoxia for 48 h, the mRNA and protein levels of HIF-1αwere decreased by 0.548 (P=0.016) and 0.984 (P=0.001), respectively.There were no significant changes in the mRNA levels of TGF-β1, ColⅠ, ColⅢ, VEGF,and periostin, as well as the protein level of TGF-β1. Conclusions The STS inhibits KFs proliferation in a dose-dependent manner and affects the expressions of pro-fibrogenic factors under both normoxia and hypoxia.The STS could be used as a candidate of therapeutic treatment against keloid.%目的：研究常氧和低氧下，丹参酮ⅡA磺酸钠（ sodium tanshinoneⅡA sulfonate，STS）对瘢痕疙瘩成纤维细胞（ keloid fibroblasts， KFs）增殖和促纤维化因子表达的影响，探讨STS治疗瘢痕疙瘩的可能作用。方法原代培养5例KFs，将细胞分组，分别在常氧（21％O2）和低氧（2％O2）下用不同剂量的STS（0、50、100、200、400、800μmol／L）干预48 h，采用CCK-8方法检测细胞增殖活力，同时在倒置相差显微镜下观察细胞的形态学变化。用不同剂量的STS（0、100、200μmol／L）同样干预48 h，实时定量PCR检测低氧诱导因子1α（HIF-1α）、转化生长因子β1（TGF-β1）、Ⅰ型胶原（ColⅠ）、Ⅲ型胶原（ColⅢ）、血管内皮生长因子（VEGF）、成骨细胞特异因子2（Periostin）的mRNA表达情况，蛋白质印迹法检测HIF-1α、TGF-β1蛋白的表达情况。结果低氧与常氧下的KFs增殖活力无明显差异；STS在常氧和低氧下明显抑制KFs增殖（P＜0．01），其有剂量依赖性，在低氧条件下STS的起效剂量比常氧下的高。低氧能够引起HIF-1α的mRNA和蛋白分别增加0．606（P＝0．037）、0．950（P＝0．002），VEGF mRNA上调7．256（P＝0．043），Periostin mRNA上调6．285（P＝0．006），TGF-β1蛋白增加1．641（P＝0．011），对ColⅠ和ColⅢ的mRNA的表达无明显影响。常氧下，200μmol／L的STS增加HIF-1α和Periostin的mRNA表达分别为0．750（P＝0．015）和8．553（P＝0.000），减少TGF-β1、ColⅠ和ColⅢ的mRNA表达分别为0．349（P＝0．007）、0．320（P＝0．006）、0．453（P＝0．015），对TGF-β1蛋白和VEGF mRNA表达影响不明显。低氧48 h，200μmol／L的STS使HIF-1αmRNA和蛋白表达分别减少0．548（P＝0.016）、0．984（P＝0．001），对TGF-β1 mRNA和蛋白以及ColⅠ、ColⅢ、VEGF、Periostin的mRNA表达影响不明显。结论常氧和低氧下STS对KFs的增殖均有抑制作用，并能够影响促纤维化因子的表达，可能作为治疗瘢痕疙瘩的潜在药物。
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