【摘要】：目的·探究溴結(jié)構(gòu)域蛋白4(BRD4)特異性抑制劑JQ-1對(duì)人增生性瘢痕的影響及其可能機(jī)制。方法·收集人皮膚增生性瘢痕標(biāo)本,原代培養(yǎng)皮膚瘢痕成纖維細(xì)胞,并進(jìn)行傳代培養(yǎng),予以0.1、0.5、1.0、2.0、2.5、12.5μmol/L不同濃度的JQ-1干預(yù)48 h,CCK-8試劑盒、細(xì)胞劃痕試驗(yàn)和ELISA法分別檢測(cè)JQ-1對(duì)成纖維細(xì)胞增殖、遷移、Ⅰ型膠原蛋白(COLⅠ)分泌量及TGF-β1的蛋白水平。36只裸鼠構(gòu)建瘢痕動(dòng)物模型,將臨床上獲得的瘢痕組織(1.0 cm×1.0 cm×0.5 cm)移植于裸鼠背部皮下。繼續(xù)飼養(yǎng)4周后,將裸鼠分成2組,JQ-1組和DMSO組,分別每日予以0.5μmol/L JQ-1及0.1%DMSO的瘢痕內(nèi)多點(diǎn)注射,1 mL/只。天狼猩紅染色和免疫組織化學(xué)法分別觀察瘢痕中COLⅠ/Ⅲ及α平滑肌肌動(dòng)蛋白(α-SMA)的變化情況。結(jié)果·細(xì)胞實(shí)驗(yàn)表明:(1)0.5μmol/L及以上濃度JQ-1對(duì)成纖維細(xì)胞增殖有明顯抑制作用(均P0.01)。(2)JQ-1可抑制成纖維細(xì)胞的遷移活性(均P0.01)。(3)JQ-1可抑制成纖維細(xì)胞COLⅠ的分泌及TGF-β1的產(chǎn)生(均P0.01)。動(dòng)物實(shí)驗(yàn)表明:(1)JQ-1組COLⅠ/Ⅲ總含量較DMSO組顯著下降,且COLⅠ/Ⅲ比值下降(均P0.05)。(2)JQ-1組α-SMA的含量較對(duì)照組明顯下降(均P0.05)。結(jié)論·JQ-1可抑制體外人瘢痕成纖維細(xì)胞的增殖、遷移、COLⅠ的分泌及TGF-β1的產(chǎn)生;其對(duì)裸鼠體內(nèi)的人瘢痕組織中COLⅠ/Ⅲ的分泌及成纖維細(xì)胞向肌成纖維細(xì)胞的轉(zhuǎn)化亦有抑制作用。
[Abstract]:Objective to investigate the effect of JQ-1, a specific inhibitor of bromine domain protein 4 (BRD4), on human hypertrophic scar and its possible mechanism. Methods Human skin hypertrophic scar specimens were collected and primary cultured skin scar fibroblasts were cultured and cultured. The cells were treated with 0.1U 0.5U 1.0 渭 mol/L and 2.5 渭 mol/L JQ-1 for 48 h CCK-8 intervention. The proliferation and migration of fibroblasts induced by JQ-1, the secretion of type I collagen (COL 鈪，

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