载脂蛋白E基因敲除小鼠血管外膜成纤维细胞G蛋白信号调节因子3,5的表达变化

Expression of RGS3 and RGS5 in Adventitial Fibroblasts of ApoE(-/-) Mice

目的:检测载脂蛋白E基因敲除小鼠(apoE(-/-))血管外膜成纤维细胞中G蛋白信号调节因子(regulator of G protein signaling,RGS)3,5的变化,探讨其在动脉粥样硬化发病中的作用。方法:体外培养高脂喂养2周的apoE(-/-)小鼠和C57BL/6小鼠动脉外膜成纤维细胞,利用基因芯片技术分析RGS3,RGS5mRNA的变化,通过RT-PCR进一步验证。结果:基因芯片数据分析显示,apoE(-/-)小鼠成纤维细胞中RGS3表达下调,与C57BL/6小鼠比值为0.46。RGS5表达上调,与C57BL/6小鼠比值为2.25。RT-PCR结果显示apoE(-/-)小鼠成纤维细胞RGS3mRNA水平低于对照组小鼠(比值为0.78),RGS5mRNA水平高于对照组小鼠(比值为2.34),与基因芯片检测结果相比,变化方向一致。结论:apoE(-/-)小鼠血管外膜成纤维细胞中选择性RGS3降低和RGS5升高可能与外膜成纤维细胞的激活密切相关,从而参与了动脉粥样硬化的发生与发展,RGS有可能成为动脉粥样硬化药物治疗及基因治疗的新靶点。

Objective： To study the effect of regulator of G protein signaling 3,5 on atherogenesis by examing the expression of RGS3 and RGS5. Methods： The arterial adventitial fibroblasts derived from apoE （-/-） mice and C57BL/6 mice after hyperlipidic diet for 2 weeks were cultured. The expression of RGS3 arid RGS5 mRNA was observed from the gene chip. RT-PCR was used to validate the result of gene chip. Results： The result of gene chip showed that RGS3 mRNA was down-regulated （ratio=0.46） and RGS5 mRNA was upregulated （ratio=2.25） in apoE （-/-） mice.The result of RT-PCR was coincident with the result of gene chip. The respective ratio was 0.78 and 2.34. Conclusion： The expression of RGS3 selectively down-regulated and RGS5 selectively up-regulated in apoE（-/-） mice may be closely related to the activation of the adventitial fibroblasts that participates in the atherosclerotic lesion formation and development.It may make RGS suitable for novel drug targets and gene therapy aimed at preventing and treating atherosclerosis.