Affymetrix基因芯片研究高血压对小鼠血管基因表达的影响

目的:利用基因芯片技术研究高血压早期血管损伤中基因表达变化。方法:30只8周龄雄性C57BL/6J小鼠,分为对照组和Ang II(血管紧张素II)组,采用置入式胶囊渗透压泵分别灌注0.9%氯化钠液和Ang II(1 500 ng·kg-1·min-1),于第3天,第7天取胸主动脉,提取核糖核酸(RNA),进行基因芯片分析;利用鼠尾套法检测Ang II灌泵3 d及7 d后小鼠尾动脉血压、苏木精伊红染色(HE)染色检测血管结构;实时定量聚合酶链式反应(PCR)验证Ang II灌泵7 d时部分芯片结果。结果:与对照组相比,Ang II组在灌泵7 d时血压升高(104±4)vs.(146±6)mmHg(1mmHg=0.133kPa),P0.001];基因芯片结果显示3d时有67个基因表达上调,27个基因表达下调,7d时有31个基因表达上调,没有检测下调基因;PCR验证磷酸分泌蛋白1(SPP1),金属蛋白酶组织抑制因子1(Timp1),4域跨膜超家族A,4C(MS4a4c),胰岛素样生长因子结合蛋白2(Igfbp2),重组激活基因1(Rag1)均表达升高。结论:Ang II导致高血压情况下,血管组织基因表达变化,可能参与高血压血管损伤的过程。

Microarray analysis on the expression of gene in mice vascular of hypertension

Objective：To identify the genes of which responsible for hypertension induced vascular injury.Methods：30 C57BL/6J male mice were randomly divided into control group （n =12） and angiotensin Ⅱ group （n =18）,using osmotic mini-pumps were implanted capsules infusion saline and Ang Ⅱ 1 500 ng.kg-1 · min-1 ; Blood pressure was measured by tail-cuff plethysmography method.At day 3 and 7,Ang Ⅱ-or salinetreated mice were euthanized,and the mRNAs were isolated from thoracic aorta and were analyzed by microarray.At day 7,the mRNA expression of SPP1,Timpl,MS4a4c,Igfbp2,Rag1 were analyzed for real-time PCR.Results：Compared with the control group,blood pressure was significantly increased at 7 days after Ang Ⅱ infusion （104 ± 4） vs.（146 ± 6） mmHg （1mmHg =0.133 kPa）,P ＜ 0.001] ; Microarray analysis showed that 67 genes were upregulated and 27 genes were downregulated in 3 days and there were 31 genes upregulated after Ang Ⅱ infused 7 days; Real-time PCR confirmed that SPP1,Timp1,MS4a4c,Igfbp2,Rag1 expression in aorta after 7 days Ang Ⅱ-infused animals were significantly increased.Conclusion：Ang Ⅱ infusion leads to hypertension and increases many genes expression,these multifunctional genes could be responsible for hypertension-induced vascular injury.