苏拉明通过抑制纤维增生和炎症反应减轻小鼠的瘢痕增生  

Suramin alleviates hypertrophic scar in mice by inhibiting fibroplasia and inflammatory response

作　　者：林康[1] 苏海燕 虞庆[1] 蒋良福[1] 高伟阳[1] LIN Kang;SU Hai-yan;YU Qing;JIANG Liang-fu;GAO Wei-yang(Department of Hand Plastic Surgery,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China;Department of Children’s Endocrinology,The Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325000,China)

机构地区：[1]温州医科大学附属第二医院手外整形科,浙江温州325000 [2]温州医科大学附属第二医院儿童内分泌科,浙江温州325000

出　　处：《中国病理生理杂志》2019年第11期2070-2077,共8页Chinese Journal of Pathophysiology

基　　金：温州市公益性科技计划项目(No.Y20150240)

摘　　要：目的:探讨苏拉明对增生性瘢痕(HPS)的治疗作用及其机制。方法:使用机械牵拉的方法制造小鼠HPS模型后,分别在瘢痕部位涂抹低剂量(5 mg/kg)和高剂量(10 mg/kg)苏拉明溶液,每天1次,持续10 d。宏观观察瘢痕增生的程度;苏木精-伊红(HE)染色评价HPS组织中瘢痕横截面积与瘢痕抬高指数;然后通过免疫组化法检测HPS组织中转化生长因子β1(TGF-β1)和白细胞介素6(IL-6)的表达水平;免疫荧光、RT-qPCR和Wes-tern blot法分别检测HPS组织中α-平滑肌肌动蛋白(α-SMA)的表达水平;ELISA检测HPS组织中肿瘤坏死因子α(TNF-α)、IL-6、IL-10和TGF-β1的含量。结果:大体观察可见,低、高剂量苏拉明治疗后HPS小鼠瘢痕表面积均显著减少(P<0.01);HE染色下可见低、高剂量苏拉明治疗后HPS小鼠瘢痕横截面积和瘢痕抬高指数均显著减少(P<0.05或P<0.01);免疫荧光染色、RT-qPCR和Western blot结果显示,低、高剂量苏拉明治疗后HPS小鼠瘢痕组织中α-SMA阳性细胞数及α-SMA mRNA表达和蛋白表达均显著降低(P<0.05或P<0.01);免疫组化结果显示,低、高剂量苏拉明治疗后HPS小鼠瘢痕组织中TGF-β1和IL-6表达均显著降低(P<0.01);ELISA结果显示,低、高剂量苏拉明治疗后HPS小鼠瘢痕组织中TNF-α、IL-6、IL-10和TGF-β1水平均显著降低(P<0.01)。结论:苏拉明具有抑制HPS形成的作用,这一作用可能与其抑制纤维增生和减轻局部炎症反应有关。AIM: To investigate the therapeutical effect of suramin on hypertrophic scar(HPS) and its mechanism. METHODS: After the mouse model of HPS was established by mechanical stretching, the suramin solution at low dose(5 mg/kg) and high dose(10 mg/kg) was applied onto the scar site caused by mechanical load in mice by transdermal administration once a day for 10 d. The degree of scar hyperplasia was observed by macroscopy. The scar cross-sectional area and scar elevation index in the HPS tissues were evaluated by hematoxylin-eosin(HE) staining. The expression levels of transforming growth factor-β1(TGF-β1) and interleukin-6(IL-6) in HPS tissues were detected by immumohistochemical staining. The expression level of α-smooth muscle actin(α-SMA) in HPS tissues was detected by immunofluorescence staining, RT-qPCR and Western blot. The levels of tumor necrosis factor-α(TNF-α), IL-6, IL-10 and TGF-β1 in the HPS tissues were measured by ELISA. RESULTS: Macroscopic observation showed that the surface areas of scar in the HPS mice after treatment with suramin at low and high doses were significantly reduced(P<0.01). HE staining results showed that the scar cross-sectional area and the scar elevation index of HPS mice after treatment with suramin at low and high doses were significantly reduced(P<0.05 or P<0.01). The results of immunofluorescence staining, RT-qPCR and Western blot showed that the number of α-SMA positive cells and the mRNA and protein expression of α-SMA in scar tissues of HPS mice after treatment with suramin at low and high doses were significantly decreased(P<0.05 or P<0.01). The results of immunohistochemical staining showed that the expression levels of TGF-β1 and IL-6 in scar tissues of HPS mice after treatment with suramin at low and high doses were significantly reduced(P<0.01). The results of ELISA showed that the levels of TNF-α, IL-6, IL-10 and TGF-β1 in the scar tissues of HPS mice after treatment with suramin at low and high doses were significantly reduced(P<0.01). CONCLUSION: Suramin

关 键 词：苏拉明 纤维增生 炎症反应 增生性瘢痕 

分 类 号：R363.2[医药卫生—病理学] R364.3[医药卫生—基础医学]