Reist R H, Dey R D, Durham J P, Rojanasakul Y, Castranova V
Department of Physiology, West Virginia University Health Sciences Center, Morgantown 26506.
Toxicol Appl Pharmacol. 1993 Sep;122(1):70-6. doi: 10.1006/taap.1993.1173.
Tetrandrine, an herbal drug, has been employed in China to treat pulmonary fibrosis. To date, the mechanisms governing the antifibrotic action of tetrandrine are unknown. The present study employs a fibroblast mitogenic assay to determine whether tetrandrine directly inhibits the ability of fibroblasts to respond to stimulation by growth factors. The data indicate that tetrandrine blocks proliferation and the incorporation of tritiated thymidine into DNA by fibroblasts stimulated with human serum, PDGF plus plasma, FGF plus plasma, or TNF plus plasma. Since tetrandrine inhibits the response to a variety of growth factors, its action does not appear to involve the blockade of a specific stimulatory receptor. Tetrandrine is effective in inhibiting thymidine incorporation when added up to 6 hr after stimulation of quiescent cells, suggesting either that tetrandrine does not block the attainment of competence by fibroblasts or that its activity is not limited to blocking the attainment of competence by these cells. Growth factor-induced mitogenesis is also inhibited by nitrendipine, a calcium channel blocker, and by cytochalasin B, a microfilament blocker. However, tetrandrine treatment of fibroblasts neither results in the changes of morphology seen with cytochalasin B nor is limited to the early events of stimulus-response coupling. Therefore, the mechanism of action for tetrandrine is not identical to that for either cytochalasin B or nitrendipine. In summary, these results suggest that the antifibrotic action of tetrandrine may be mediated in part by direct inhibition of fibroblast proliferation normally associated with the development and progression of silicosis.
粉防己碱是一种草药，在中国已被用于治疗肺纤维化。迄今为止，粉防己碱抗纤维化作用的机制尚不清楚。本研究采用成纤维细胞促有丝分裂试验，以确定粉防己碱是否直接抑制成纤维细胞对生长因子刺激的反应能力。数据表明，粉防己碱可阻断人血清、血小板衍生生长因子（PDGF）加血浆、成纤维细胞生长因子（FGF）加血浆或肿瘤坏死因子（TNF）加血浆刺激的成纤维细胞的增殖以及氚标记胸腺嘧啶核苷掺入DNA的过程。由于粉防己碱抑制对多种生长因子的反应，其作用似乎不涉及阻断特定的刺激受体。在静止细胞受到刺激后长达6小时添加粉防己碱时，它能有效抑制胸腺嘧啶核苷掺入，这表明粉防己碱要么不阻断成纤维细胞获得反应能力，要么其活性不限于阻断这些细胞获得反应能力。生长因子诱导的有丝分裂也受到钙通道阻滞剂尼群地平和微丝阻滞剂细胞松弛素B的抑制。然而，用粉防己碱处理成纤维细胞既不会导致细胞松弛素B所引起的形态变化，也不限于刺激-反应偶联的早期事件。因此，粉防己碱的作用机制与细胞松弛素B或尼群地平的作用机制不同。总之，这些结果表明，粉防己碱的抗纤维化作用可能部分是通过直接抑制通常与矽肺发生和发展相关的成纤维细胞增殖来介导的。
