甘草次酸减轻放射性皮肤纤维化的作用机制

Mechanism of Action of Glycyrrhetinic Acid Alleviating Radiation-Induced Skin Fibrosis

目的探讨18β-甘草次酸(18β-GA)减轻放射性皮肤纤维化的作用机制。方法以X射线照射小鼠背部皮肤构建放射性皮肤纤维化的动物模型,采用苏木精-伊红(H-E)染色和马松(Masson)染色评估小鼠背部皮肤组织的病理情况,免疫组织化学法检测各组小鼠皮肤组织中的α-平滑肌肌动蛋白(α-SMA)表达。以X射线照射小鼠胚胎成纤维细胞(NIH 3T3)构建放射性皮肤纤维化的细胞模型,采用凝胶收缩试验检测细胞收缩,免疫荧光检测α-SMA的表达,Western-blot检测皮肤组织中α-SMA、Ⅰ型胶原(ColⅠ)和纤维连接蛋白(FN)的表达。结果18β-GA能减轻小鼠放射性皮肤纤维化程度,减少照射后小鼠皮肤组织中α-SMA的表达,抑制照射后NIH 3T3细胞内α-SMA、ColⅠ和FN的表达,减少细胞收缩。结论18β-GA具有减轻放射性皮肤纤维化的作用,其机制可能与抑制成纤维细胞活化有关。

Objective To investigate the mechanism of 18β-glycyrrhetinic acid(18β-GA)in alleviating radiation-induced skin fibrosis.Methods The animal model of radiation-induced skin fibrosis was constructed by irradiating the dorsal skin of mice with X-rays.Hematoxylin-eosin staining(H-E)and Masson staining were used to assess dorsal skin pathology of mice,and the expression ofα-smooth muscle actin(α-SMA)in the skin tissue of each group of mice was detected by immunohistochemistry.Cellular model of radiation-induced skin fibrosis was constructed by irradiating mouse embryonic fibroblasts(NIH 3T3)with X-rays.The contractility of cells was assessed by gel contraction test,and the expression ofα-SMA was detected by immunofluorescence.The expression ofα-SMA,CollagenⅠ(ColⅠ)and fibronectin(FN)were detected by Western-blot analysis.Results 18β-GA alleviated radiation-induced skin fibrosis in mice and significantly reduced the expressions ofα-SMA,ColⅠand FN in the irradiated skin of mice.It also inhibited the expressions ofα-SMA in irradiated NIH 3T3 cells and reduced cell contractility.Conclusion 18β-GA showed an alleviating effect on radiation-induced skin fibrosis,and the anti-fibrotic effect may be related to the inhibition of fibroblast activation.