Lim Kyungjoon, Zimanyi Monika A, Black M Jane
Department of Anatomy and Cell Biology, Monash University, Clayton, Victoria, Australia.
Pediatr Res. 2006 Jul;60(1):83-7. doi: 10.1203/01.pdr.0000220361.08181.c3. Epub 2006 May 11.
This study examines the effect of maternal protein restriction in rats on levels of cardiac fibrosis, myocardial capillarization, and media:lumen ratio of intramyocardial arteries in adult offspring. Female Wistar Kyoto rats were fed either a normal protein diet (NPD; 20% casein) or a low-protein diet (LPD; 8.7% casein) during pregnancy and lactation. Female offspring (seven per group) were weaned at 4 wk of age and grown to adulthood. At 24 wk of age, the offspring were perfusion fixed. Cardiac fibrosis and media:lumen ratio of intramyocardial arterioles was assessed using image analysis and cardiac capillarization was stereologically investigated. Body weights at 2 and 24 wk of age were significantly reduced (31% and 8%, respectively) in the LPD offspring; however, heart size was not different at 24 wk. Importantly by adulthood, there was a significant 15% increase in left ventricular interstitial fibrosis in LPD offspring. There were no differences in levels of perivascular fibrosis, myocardial capillarization, or in the media:lumen ratio of intramyocardial arteries between groups. Because cardiac fibrosis is associated with impaired cardiac contractility and arrhythmia, our results suggest that induction of interstitial fibrosis may contribute to the increased cardiac disease in adult subjects who were exposed to an adverse intrauterine environment.
本研究考察了孕期蛋白质限制对成年子代大鼠心脏纤维化水平、心肌毛细血管化以及心肌内动脉中膜与管腔比值的影响。雌性Wistar Kyoto大鼠在怀孕和哺乳期分别喂食正常蛋白质饮食（NPD；20%酪蛋白）或低蛋白质饮食（LPD；8.7%酪蛋白）。雌性子代（每组7只）在4周龄时断奶并成长至成年。在24周龄时，对这些子代进行灌注固定。使用图像分析评估心肌内小动脉的心脏纤维化和中膜与管腔比值，并通过体视学方法研究心脏毛细血管化情况。LPD组子代在2周龄和24周龄时的体重显著降低（分别降低31%和8%）；然而，在24周龄时心脏大小并无差异。重要的是，到成年时，LPD组子代的左心室间质纤维化显著增加了15%。两组之间在血管周围纤维化水平、心肌毛细血管化或心肌内动脉的中膜与管腔比值方面没有差异。由于心脏纤维化与心脏收缩功能受损和心律失常有关，我们的结果表明，间质纤维化的诱导可能导致成年期暴露于不良子宫内环境的个体患心脏病的风险增加。
