Sauvage M, Jacob M P, Osborne-Pellegrin M
INSERM U367, Paris, France.
J Vasc Res. 1997 Mar-Apr;34(2):126-36. doi: 10.1159/000159215.
We have previously characterized two normotensive strains of rats which differ markedly in their susceptibility to spontaneous rupture of the internal elastic lamina (IEL), the Brown Norway (BN) being very susceptible and the Long Evans (LE) being resistant. Here we quantified biochemically the elastin and collagen content of aortae from adult male BN and LE rats aged 12, 18 and 22 weeks and showed that the elastin content was lower and the collagen content higher in the BN strain than in the LE strain, resulting in a markedly lower elastin/collagen ratio in the former strain. These modifications were present both in the thoracic aorta, which is devoid of IEL ruptures, and in the abdominal segment where ruptures frequently occur in the BN rat, suggesting that they could represent a predisposing factor in the presence of other local factors. Quantifications of relevant mRNAs in aortae of younger male BN and LE rats by Northern blot showed that there are lower tropoelastin transcript levels in the BN rat at 6 weeks in both thoracic and abdominal segments than in the age-matched LE rat. In contrast there was no consistent interstrain difference in alpha 1 type I collagen transcripts and alpha 1 type III collagen transcripts were higher in the BN aorta only at 6 weeks in the abdominal segment. We conclude that the BN rat presents an aortic elastin deficit which appears to be in part explained by a decreased elastin synthesis in young, growing rats and may be genetically determined. However, a direct relation of this elastin deficit with susceptibility to rupture of the IEL cannot be concluded from this study.
我们之前已对两种血压正常的大鼠品系进行了特征描述，它们在内弹性层（IEL）自发性破裂的易感性上存在显著差异，其中布朗挪威大鼠（BN）非常易感，而长 Evans 大鼠（LE）具有抗性。在此，我们对 12 周、18 周和 22 周龄的成年雄性 BN 和 LE 大鼠主动脉的弹性蛋白和胶原蛋白含量进行了生化定量分析，结果显示，BN 品系的弹性蛋白含量低于 LE 品系，而胶原蛋白含量高于 LE 品系，导致前者的弹性蛋白/胶原蛋白比值明显更低。这些改变在没有 IEL 破裂的胸主动脉以及 BN 大鼠中经常出现破裂的腹主动脉段均存在，这表明在存在其他局部因素的情况下，它们可能是一个易感因素。通过 Northern 印迹法对年轻雄性 BN 和 LE 大鼠主动脉中相关 mRNA 的定量分析表明，在 6 周龄时，BN 大鼠胸主动脉和腹主动脉段的原弹性蛋白转录水平均低于年龄匹配的 LE 大鼠。相比之下，α1 型 I 胶原蛋白转录本在品系间没有一致的差异，而α1 型 III 胶原蛋白转录本仅在 6 周龄时在 BN 大鼠腹主动脉段中更高。我们得出结论，BN 大鼠存在主动脉弹性蛋白缺陷，这似乎部分是由于幼年生长大鼠中弹性蛋白合成减少所致，并且可能是由基因决定的。然而，从本研究中无法得出这种弹性蛋白缺陷与 IEL 破裂易感性之间的直接关系。
