摘要目的研究转单基因和转双基因小鼠外周微血管反应性改变的作用机制.方法在未转基因、转单基因和转双基因小鼠的后足爪垫皮肤暴露微血管网,灌注血管扩张剂乙酰胆碱和硝普钠,多普勒检测血液流量变化,应用Western blot检测小鼠外周血β-淀粉样蛋白(Aβ)水平.结果与未转基因和转单基因(表达SOD1基因突变子G93A)小鼠相比,2-3月龄转单基因(表达APP -C100、TgC100)和转双基因(APP-C100和SOD1基因突变子G93A基因共表达)小鼠外周血液流量下降28%,8-9月龄TgC100小鼠外周血液流量减少34%,TgC100和转双基因小鼠外周血A β水平较未转基因小鼠明显升高,差异有显著性意义(P<0.01).结论 TgC100和转双基因小鼠外周血管反应性的改变很可能由循环性可溶性Aβ引起,Aβ血管活性涉及内皮和非内皮机制.

abstractsObjective To explore the mechanism underlying changes in microvascular reactivity in singl e- and double-transgenic mice.Methods Peripheral vascular reactivity to the vasodilators, acetylcholine and sodium nit roprusside, on perfused microvasculature of the hind footpad was investigated us ing nontransgenic mice, single-transgenic mice expressing the human APP-C100 ( TgC100.WT or TgC100.V717F) and double-transgenic mice coexpressing human APP -C100 and human SOD1 (G93A) genes.Results Single TgC100 and double Tg mice C100/SOD1 (G93A) at 2-3 months old showed a s tatistical decrease of 28% in blood flux compared to nontransgenic control mice . In addition, vasodilative responsiveness was markedly reduced to 34% in 8-9 m onths old TgC100 mice compared to control mice. There was no significant differ ence in the profile of vasodilative reaction between TgC100.WT and TgC100.V717 F mice. TgC100 and double Tg mice also had higher levels of Aβ peptide in plas ma than nontransgenic mice (P<0.01).Conclusions The present study suggests that the altered reactivity of the microvasculature m ay be mediated by circulating soluble Aβ peptides. The mechanisms underlying t h e vasoactivity of circulating Aβ in TgC100 and double Tg mice may involve both the endothelium and nonendothelium.