利用基因芯片筛选动脉钙化大鼠差异表达基因

摘要

目的：利用基因芯片技术筛选正常大鼠和动脉钙化大鼠腹主动脉组织中差异表达基因及检测转化生长因子－β（TGF－β）、基质金属蛋白酶－2（MMP－2）和基质金属蛋白酶－9（MMP－9）的表达量，以探讨动脉钙化发病的可能机制。方法通过皮下注射大剂量维生素D3建立大鼠动脉钙化模型，采用Von Kossa染色观察动脉钙化程度，基因芯片技术筛选两组大鼠差异表达基因及检测TGF－β、MMP－2和MMP－9的表达量。结果与对照组相比，模型组差异表达的基因有710条，其中上调基因344条，下调基因366条。模型组TGF －β1、TGF－β3和MMP－2的表达均明显上调，差异具有统计学意义（P＜0.05），而TGF－β2和MMP－9的表达则无明显差异（P＞0.05）。结论动脉钙化的形成是多基因共同作用的结果，其中TGF－β、MMP－2和MMP－9对动脉钙化的发生发展起着至关重要的作用，其机制还有待进一步研究。%Objective To investigate the possible mechanism of arterial calcification by screening differentially expressed genes and detecting the expression levels of transforming growth factor beta ( TGF-β) , matrix metalloprotein-ase-2 ( MMP-2 ) and matrix metalloproteinase-9 ( MMP-9 ) between normal rats and rats with artery calcification through gene chip technology.Methods Arterial calcification in rats was induced by subcutaneous injection of large dose of vitamin D3 .The extent of artery calcification was determined by Von Kossa staining.Differentially expressed genes and the expression levels of TGF-β, MMP-2 and MMP-9 between normal rats and rats with arterial calcification were de-tected through gene chip technology.Results Compared with the control group, 710 genes were differentially expressed in the model group.344 were up-regulated and 366 were down-regulated.Expression levels of TGF-β1, TGF-β3, and MMP-2 in the model group were significantly up-regulated ( P<0.05) , while TGF-β2 and MMP-9 expression levels showed no significant difference between the two groups (P>0.05).Conclusion Multiple gene interaction con-tributes to the formation of artery calcification.Among them, TGF-β, MMP-2 and MMP-9 play a pivotal role in the pathogenesis of artery calcification.However, the mechanism still remains to be further explored.