钙调神经磷酸酶对钙化血管蛋白激酶G表达的影响.docVIP

钙调神经磷酸酶对钙化血管蛋白激酶G表达的影响 　　作者：苑晓烨 李绍冰 曾强 李芳 姚丽霞 杨爽 郑敬 陈丽 刘彩霞 作者单位：河北省人民医院老年心血管病科，河北 石家庄 050051 　　【摘要】 　　目的 探讨钙调神经磷酸酶(CaN)对钙化血管蛋白激酶G IΑ (PKG IΑ) 蛋白及mRNA表达的影响。方法 SD雄性大鼠分为对照组、钙化组及环孢霉素A(CsA)组。采用华法林和维生素D3建立大鼠主动脉钙化模型。9 d后HE染色及VonKossa染色观察血管形态及钙沉积改变，应用免疫组化法测定PKGⅠΑ蛋白及CaNB1蛋白，原位杂交法测定PKGⅠΑ及CaNAΑ mRNA，测定CaN和碱性磷酸酶(ALP)活性。结果 钙化组PKG IΑ蛋白和mRNA表达明显减少，与对照组比较，差异有统计学意义(P0.01)，CaNB1蛋白和CaNAΑ mRNA表达明显增加，与对照组比较，差异有显著性(P0.05)。结论 CaN能够抑制钙化血管中PKG IΑ蛋白及mRNA的表达。 　　【关键词】 华法林;维生素D3;血管钙化;钙调神经磷酸酶;环鸟苷酸依赖的蛋白激酶;环孢霉素A 　　Regulation of expression of cGMPdependent protein kinase IΑ by calcineurin in vascular calcification 　　YUAN XiaoYe, LI ShaoBing, ZENG Qiang, et al. 　　Cardiovascular Department of Gerontology, Hebei Provincial People′s Hospital，Shijiazhuang 050051，Hebei，China 　　【Abstract】 Objective To discuss the regulation of expression of cGMPdependent protein kinase IΑ (PKG IΑ protein and mRNA) by calcineurin (CaN) in vascular calcification. Methods Rat vascular calcification model was made by subcutaneously injection of warfarin and Vitamin D3. 4weeksold male SD rats were randomly divided into 3 groups: normal control, calcification and CsA groups. Samples from 6 rats of each group were used for immunohistochemistry to examine the expressions of PKGⅠΑ protein and CaNB1 protein as well as for in situ hybridization to detect the expressions of PKGⅠΑ mRNA and CaNAΑ mRNA. The others were used to detect activities of CaN and alkaline phosphatase (ALP) in rat aorta. Results Expressions of PKGⅠΑ　protein and mRNA in rat aorta from calcification group depressed, and expressions of CaNB1 protein, CaNAΑ mRNA was elevated significantly. Conclusions CaN can inhibit the expression of PKG IΑ protein and mRNA in vascular calcification. 　　【Key words】 Warfarin; Vitamin D3; Vascular calcification; cGMPdependent protein kinase;Calcineurin; Cyclosporin A 　　血管钙化是动脉粥样硬化、糖尿病、肾病、衰老、收缩期高血压及骨质疏松等多种疾病的病理基础，尤其与动脉粥样硬化关系密切，可以导致血栓形成、粥样硬化斑块破裂等严重后果。血管钙化与骨代谢及血管平滑肌细胞 (VSMC) 表型转换关系密切。环三磷酸鸟苷依赖的蛋白激