Holzenberger M, Dumanois-Le Tan V, Ayer-Lelièvre C, Vincent M, Safar M, Renaud J F
Institut d'embryologie cellulaire et moléculaire, CNRS UMR 9924 et Collège de France, Nogent-sur-Marne.
Arch Mal Coeur Vaiss. 1996 Aug;89(8):991-6.
Experimental pharmacology and studies on hypertension frequently use genetically hypertensive animal models like the SHR or the Lyon hypertensive rat LH. In order to further characterize these two models we measured the expression levels of three major extracellular matrix components in the aortic wall, tropoelastin (TE) and type I and type III collagen, during postnatal development. The type I collagen expression decreases progressively during the first twelve weeks of postnatal development without significant differences between SHR and LH, or their normotensive controls, WKY or LN respectively. No differences were detected either for the expression levels of TE and type III collagen between the hypertensive strains and their respective controls. However, direct comparison of the two hypertensive strains SHR and LH, revealed a specific, strong increase of TE and type III expression for the LH at 5 and 12 weeks (p < 0.001 and 0.005 respectively). The evolution of the ratios of expression levels between the two collagens (type III/type I) on one side and of TE and collagen type I (TE/type I) on the other side were similar for the hypertensive strains and their respective controls, but diverged significantly for LH and SHR animals (up to p < 0.001 depending on the age group). Both indicators, III/I and TE/I, are considerably higher in LH compared to SHR from 5 weeks of postnatal development onwards. Our results indicate that the genes for TE and type I and III collagen are regulated during postnatal development of LH and SHR. It is however not possible at this point to establish a link between mRNA levels and hypertension in these animals. Nevertheless, the ratios III/I and TE/I seem to be good phenotypic markers for the characterisation of LH and SHR strains.
实验药理学及高血压研究经常使用遗传性高血压动物模型,如自发性高血压大鼠(SHR)或里昂高血压大鼠(LH)。为了进一步表征这两种模型,我们测量了出生后发育过程中主动脉壁中三种主要细胞外基质成分——原弹性蛋白(TE)、I型和III型胶原蛋白的表达水平。I型胶原蛋白的表达在出生后发育的前十二周逐渐下降,SHR和LH之间或它们的正常血压对照(分别为WKY和LN)之间没有显著差异。在高血压品系及其各自对照之间,TE和III型胶原蛋白的表达水平也未检测到差异。然而,对两种高血压品系SHR和LH的直接比较显示,LH在5周和12周时TE和III型表达有特异性的强烈增加(分别为p < 0.001和0.005)。两种胶原蛋白(III型/I型)之间以及TE和I型胶原蛋白(TE/I型)之间表达水平的比值变化,在高血压品系及其各自对照中相似,但在LH和SHR动物中差异显著(根据年龄组,差异高达p < 0.001)。从出生后发育5周起,LH中的III/I和TE/I这两个指标均明显高于SHR。我们的结果表明,TE、I型和III型胶原蛋白的基因在LH和SHR出生后发育过程中受到调控。然而,目前还无法在这些动物中建立mRNA水平与高血压之间的联系。尽管如此,III/I和TE/I比值似乎是表征LH和SHR品系的良好表型标志物。