Trivedy C, Meghji S, Warnakulasuriya K A, Johnson N W, Harris M
Department of Oral Medicine and Pathology/WHO Collaborating Center for Oral Cancer and Precancer, The Guy's, King's, St Thomas' School of Dentistry, King's College London, England.
J Oral Pathol Med. 2001 Sep;30(8):465-70. doi: 10.1034/j.1600-0714.2001.030008465.x.
Copper is implicated in the pathogenesis of several fibrotic disorders. Areca nut has been shown to have a high copper content and areca chewing is associated with oral submucous fibrosis (OSF). The effects of copper on human oral fibroblasts were investigated in vitro. Human oral fibroblasts were incubated with copper chloride (CuCl2) at concentrations ranging from 0.01 microM to 500 microM for 24 h, and in vitro cell proliferation was assayed by incorporation of tritiated-thymidine; soluble and non-soluble collagen synthesis was assayed using tritiated-proline. Addition of copper chloride at concentrations ranging from 0.1 microM to 50 microM increased the collagen synthesis by the oral fibroblasts compared with growth without copper (P<0.05). The addition of copper chloride neither increased the synthesis of non-collagenous proteins by the fibroblasts nor influenced their proliferation rate. We conclude that copper upregulates collagen production in oral fibroblasts. This appears to be concentration dependent, with peak collagen synthesis at 50 microM CuCl2. These in vitro results taken together with the recent findings of copper in oral biopsies from OSF subjects support the hypothesis that copper in areca nut acts as a mediator of OSF.
铜与多种纤维化疾病的发病机制有关。槟榔已被证明含有高含量的铜，咀嚼槟榔与口腔黏膜下纤维化（OSF）有关。本研究在体外探究了铜对人口腔成纤维细胞的影响。将人口腔成纤维细胞与浓度范围为0.01微摩尔/升至500微摩尔/升的氯化铜（CuCl2）孵育24小时，通过掺入氚标记胸腺嘧啶核苷检测体外细胞增殖；使用氚标记脯氨酸检测可溶性和不可溶性胶原蛋白的合成。与无铜培养相比，添加浓度范围为0.1微摩尔/升至50微摩尔/升的氯化铜可增加口腔成纤维细胞的胶原蛋白合成（P<0.05）。添加氯化铜既不增加成纤维细胞非胶原蛋白的合成，也不影响其增殖率。我们得出结论，铜上调口腔成纤维细胞中的胶原蛋白产生。这似乎具有浓度依赖性，在50微摩尔/升CuCl2时胶原蛋白合成达到峰值。这些体外研究结果与近期在OSF患者口腔活检中发现的铜的结果相结合，支持了槟榔中的铜作为OSF介质的假说。
