贝前列素对心肌成纤维细胞胶原交联的影响及机制研究
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江苏省高校自然科学基金(12KJB310012);南通市自然科学基金(BK2011044,BK2012087)


Effects and mechanisms of beraprost on cross linked collagen in cardiac fibroblasts
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    摘要:

    目的:观察贝前列素对血管紧张素Ⅱ(angiotensin Ⅱ,AngⅡ)刺激下心肌成纤维细胞胶原交联的影响并初步探讨其机制。方法:体外培养新生大鼠心肌成纤维细胞,给予贝前列素预处理后,AngⅡ(100 nmol/L)再刺激24 h,测定细胞培养基中胶原含量和交联程度,实时荧光定量PCR和Western blot法测定赖氨酰氧化酶(lysyl oxidase,LOX) mRNA和蛋白表达。结果:贝前列素可剂量依赖性地抑制Ang Ⅱ刺激下心肌成纤维细胞胶原分泌,其中10 μmol/L作用最强。贝前列素(10 μmol/L)预处理4 h后再给予AngⅡ刺激,心肌成纤维细胞胶原分泌明显减少,交联胶原水平下降,交联与非交联胶原比例变低;LOX mRNA和蛋白表达亦明显下降。结论:贝前列素抑制Ang Ⅱ刺激下心肌成纤维细胞胶原交联,机制可能与下调LOX表达有关。

    Abstract:

    Objective:To observe the effects and mechanisms of beraprost on cross linked collagen in angiotensinⅡ (AngⅡ)-stimulated cardiac fibroblasts. Methods:The cultured neonatal rat cardiac fibroblasts were pre-treated with beraprost followed with Ang Ⅱ (100 nmol/L) stimulation for 24 h. Total collagen and cross linked collagen were examined in culture medium. Lysyl oxidase (LOX) expression was determined with real time PCR and western blot. Results:Beraprost dose-dependently inhibited collagen secretion with Ang Ⅱ stimulation,among which 10 μmol/L presented with the most robust suppression. Beraprost (10 μmol/L) pre-treatment for 4 h followed with AngⅡ stimulation significantly reduced collagen secretion,as well as the cross linked degree and ratio of cross linked collagen to non-cross linked collagen,accompaying with decreasing mRNA and protein expression of LOX. Conclusion:Beraprost inhibited cross linked collagen in AngⅡ-stimulated cardiac fibroblasts,which may be associated with suppression of LOX expression.

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孟国梁,杨圣菊,姚文娟,秦巨峰,张 伟.贝前列素对心肌成纤维细胞胶原交联的影响及机制研究[J].南京医科大学学报(自然科学版),2015,(2):169-172-187

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  • 收稿日期:2014-07-13
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  • 在线发布日期: 2015-02-13
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