青蒿琥酯对增生性瘢痕成纤维细胞的抑制作用及机制探讨  

Inhibitory effects of artesunate on hypertrophic scar fibroblasts

作　　者：李战[1] 农晓琳[1] 李佳荃[2] 朴智[1] 唐黎黎[1] 

机构地区：[1]广西医科大学口腔医学院口腔颌面外科,广西南宁530021 [2]广西医科大学医学科学实验中心,广西南宁530021

出　　处：《中国药理学通报》2014年第7期947-951,共5页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 30060082);广西自然科学基金资助项目(No桂科青0447033);广西中医药科技专项重点课题(No GZKZ10-010)

摘　　要：目的研究青蒿琥酯(ART)对增生性瘢痕成纤维细胞的抑制作用及其可能机制。方法收集人皮肤增生性瘢痕标本,原代培养人皮肤增生性瘢痕成纤维细胞。用0、75、150、300、600μmol·L-1ART干预24 h,MTT法检测青蒿琥酯的细胞增殖抑制作用,荧光定量RT-PCR法检测结缔组织生长因子(CTGF)、基质金属蛋白酶1(MMP1)和Ⅰ型前胶原α2链(proCOL1A2)mRNA的表达,Western blot法检测CTGF及Ⅰ型胶原的蛋白表达。结果各测试浓度ART均可抑制成纤维细胞增殖。和对照组相比,CTGF和proCOL1A2mRNA表达降低,而MMP1表达明显升高。Western blot法检测发现CTGF及Ⅰ型胶原表达明显下调。结论 ART能抑制增生性瘢痕成纤维细胞的增殖,并下调其CTGF及Ⅰ型胶原表达,同时上调MMP1的表达;通过抑制CTGF,并促进MMP1表达而减少胶原沉积可能是ART抑制增生性瘢痕的机制之一。Aim To explore the inhibitory effect of ar-tesunate （ART）on the growth of hypertrophic scar fi-broblasts;and to elucidate its mechanisms further. Method Fibroblasts isolated from tissue specimens of hypertrophic scar were treated with ART of 0,75,150, 300,600 μmol＆·L-1 for 24h.MTT assay was used to measure the anti-proliferation effect of ART on fibro-blasts. Real-time fluorescence quantitative RT-PCR （FQ-RT-PCR）method was used to detect the mRNA expression of connective tissue growth fact （CTGF ）,α2 chain of procollagen Ⅰ （proCOL1 A2 ）and type 1 matrix metalloproteinases （MMP1 ）.The protein ex-pression of CTGF and collagen Ⅰ was detected with Western blot assessment.Results ART could inhibit the proliferation of fibroblasts in a dose-dependent manner.FQ-RT-PCR showed that the expression of＆amp;nbsp;CTGF and proCOL1 A2 mRNA was decreased by vari-ous concentrations of ART, compared with control group.Otherwise the mRNA level of MMP1 was signif-icantly increased in a dose-dependent manner at the same time.Western blot showed that the expression of CTGF and collagen Ⅰ proteins in fibroblasts was sig-nificantly decreased.Conclusion ART effectively in-hibits the growth of fibroblasts derived from hypertroph-ic scar.At the same time,ART can inhibit the deposi-tion of extracellular matrix in fibroblasts,partly by reg-ulating the expressions of CTGF and MMP1 ,which provides theoretical support for the application of ART to control hypertrophic scar.

关 键 词：增生性瘢痕 成纤维细胞 青蒿琥酯 结缔组织生长因子 基质金属蛋白酶 Ⅰ型胶原 MMP1 COLLAGEN Ⅰ 

分 类 号：R284.1[医药卫生—中药学] R329.24[医药卫生—中医学]