2018 年第 12 期 第 13 卷

消退素D1对转化生长因子β诱导的大鼠肺成纤维细胞纤维化增殖及胶原蛋白合成的抑制作用

Resolvin D1 inhibits fibroproliferation and collagen production induced by transforming growth factor-β in rat lung fibroblasts

作者：朱天琦何国栋陈蓓萍杨能力

英文作者：

单位：325000温州医科大学附属第一医院麻醉科

英文单位：

关键词：肺成纤维细胞；消退素D1；转化生长因子β；纤维化增殖

英文关键词：

• 摘要：

• 【摘要】目的    探讨消退素D1对转化生长因子β(TGF-β)诱导的大鼠原代肺成纤维细胞增殖、胶原蛋白合成以及向肌纤维母细胞转化的影响。方法    分离和培养大鼠原代肺成纤维细胞，用TGF-β（10 μg/L）干预建立成纤维细胞体外纤维化增殖模型，分别应用不同浓度(0、10、25、100 μmol/L)消退素D1作用于经TGF-β诱导的肺成纤维细胞。采用BrdU细胞增殖试剂盒测定细胞增殖；采用实时定量聚合酶链反应测定mRNA表达；同时应用蛋白质印迹法检测肺成纤维细胞胶原蛋白和α-平滑肌肌动蛋白（α-SMA）的蛋白表达。结果    消退素D1能够抑制TGF-β诱导的肺成纤维细胞增殖且呈剂量依赖性，与TGF-β组［（156.0±13.6）%］相比，TGF-β＋消退素D1 10 μmol/L组［（130.0±4.6）%］、TGF-β＋消退素D1 25 μmol/L组［（118.0±5.2）%］、TGF-β＋消退素D1 100 μmol/L组［（99.0±12.6）%］细胞增殖均明显受到抑制（均P＜0.01）。该抑制作用依赖于磷脂酰肌醇-3-激酶和消退素受体。消退素D1能够明显抑制TGF-β诱导的肺成纤维细胞的胶原蛋白合成及α-SMA表达（均P＜0.01）。结论    消退素D1抑制TGF-β诱导的大鼠肺成纤维细胞增殖、胶原蛋白合成以及向肌纤维母细胞转化标记的表达。

• 【Abstract】Objective    To explore the effect of resolvin D1 on fibroproliferation, collagen production and myofibroblast differentiation induced by transforming growth factor-β（TGF-β） in primary rat lung fibroblasts. Methods    Rat lung fibroblasts were isolated and cultured in vitro; the cells were incubated in culture medium containing TGF-β with absence or presence of resolving D1(0, 10, 25, 100 μmol/L). After incubation, cell proliferation was measured by BrdU cell proliferation kit; mRNA expression was measured by real time polymerase chain reaction; expressions of collagen and α-smooth muscle actin（α-SMA） were measured by western blotting. Results    Resolvin D1 could inhibit rat lung fibroblast proliferation induced by TGF-β in a dose-dependent manner; cell proliferation rate in TGF-β＋resolvin D1 10 μmol/L group［（130.0±4.6）%］, TGF-β＋resolvin D1 25 μmol/L group［（118.0±5.2）%］ and TGF-β＋resolvin D1 100 μmol/L group［（99.0±12.6）%］ was significantly lower than that in TGF-β-alone group［（156.0±13.6）%］（P＜0.01）. The inhibition effect was phosphatidylinositol-3-kinase dependent and resolvin receptor dependent. Resolvin D1 could reduce collagen and α-SMA protein expression induced by TGF-β（P＜0.01）. Conclusion    Resolvin D1 down-regulates fibroproliferation, collagen production and myofibroblast differentiation induced by TGF-β in rat primary lung fibroblast cells.