贝前列素通过前列环素受体抑制血管紧张素II诱导的心肌成纤维细胞增殖
孟国梁，陈云，张伟
基金项目：南通市自然科学基金（BK2011044） 作者简介：孟国梁（1981-），男，讲师，主要研究方向：心血管药理学. 

 （南通大学药学院，南通，226001）
摘要：目的：观察前列环素类似物贝前列素对管紧张素II（Ang II）诱导心肌成纤维细胞增殖的影响及机制。方法：体外培养新生大鼠心肌成纤维细胞，不同浓度贝前列素预处理后，Ang II（100 nM）刺激心肌成纤维细胞，CCK-8法测定细胞数目，收集细胞培养基中测定羟脯氨酸含量，实时荧光定量PCR法测定I型胶原和III型胶原mRNA表达，western blot及10 免疫荧光染色观察胶原蛋白表达。应用siRNA干扰技术沉默前列环素受体（IP）后，再次观察贝前列素对Ang II诱导的心肌成纤维细胞增殖的影响。结果：贝前列素能显著抑制Ang II诱导的心肌成纤维细胞增殖及I型胶原合成，但下调心肌成纤维细胞的IP表达后，贝前列素上述抑制作用不再存在。结论：贝前列素通过前列环素受体抑制Ang II诱导的心肌成纤维细胞增殖和胶原合成。

关键词：药理学；贝前列素；心肌成纤维细胞；胶原；前列环素受体
中图分类号：R96
Beraprost inhibits Ang II induced cardiac fibroblasts proliferation by activating prostacyclin receptor MENG Guolaing, CHEN Yun, ZHANG Wei
(College of pharmacy, Nantong University, Nantong, 226001)
Abstract: IObjective: To investigate the effect and mechanism of prostacyclin analogue beraprost on angiotensin II (Ang II) induced cardiac fibroblasts proliferation. Methods: Neonatal rat cardiac fibroblasts were pre-treated with different concentrations of beraprost for different times followed  by Ang II (100 nM) stimulation. Numbers of cardiac fibroblasts was determined by cell counting Kit-8 assay. Content of hydroxyproline in culture mediums was measured. Real time PCR analysis was used to measure collagen I and collagen III mRNA expression. Western blot analysis and immunofluorescence staining were used to measure collagen protein expression. After prostacyclin receptor (IP) was knocked down with siRNA technology, effect of beraprost was  investigated again. Results: Beraprost effectively inhibited angiotensin II (Ang II) induced neonatal rat cardiac fibroblasts proliferation and collagen synthesis, which was not able to be rescued if prostacyclin receptor was knocked down with siRNA technology. Conclusion: Beraprost inhibits Ang II induced cardiac fibroblasts proliferation by activating prostacyclin receptor.
Key words: Pharmacology; Beraprost; Cardiac fibroblasts; Collagen; Prostacyclin receptor