Department of Anatomy and Developmental Biology, Monash University, Clayton, Australia.
Pediatr Res. 2012 Oct;72(4):344-51. doi: 10.1038/pr.2012.94. Epub 2012 Jul 13.
Intrauterine growth restriction (IUGR) has been linked to heart disease in adulthood. Hence the IUGR heart is likely to be vulnerable to diabetic heart disease. The aim of this study was to examine the effect of induction of type 1 diabetes on myocardial collagen deposition and cardiac function in adult rats with a history of IUGR, after controlling blood glucose levels.
IUGR was induced by protein restriction in the pregnant female rat. When the offspring were 24 wk of age, diabetes was induced in male IUGR and non-IUGR rats by means of streptozotocin; insulin injections were used to maintain blood glucose levels at a mild (7-10 mmol/l; n = 8 per group) or moderate level (10-15 mmol/l; n = 8 per group). Echocardiography and cardiac morphology analyses were carried out when the rats were 32 wk of age.
IUGR offspring exhibited cardiac hypertrophy at 32 wk, including a thicker posterior wall and increased interstitial fibrosis in the left ventricle. Hyperglycemia led to an increase in heart size and myocardial fibrosis. The response to hyperglycemia was not different between IUGR and non-IUGR rats; however, cardiac fibrosis was greatest when diabetes was present along with a history of IUGR. In general, maintaining blood glucose levels at a mildly hyperglycemic level attenuated the adverse effects of hyperglycemia but did not reverse the fibrosis.
Exacerbated fibrosis in hyperglycemic hearts of IUGR offspring may lead to long-term cardiac dysfunction.
宫内生长受限（IUGR）与成年人心血管疾病有关。因此，IUGR 心脏可能容易患糖尿病性心脏病。本研究的目的是在控制血糖水平的情况下，研究 1 型糖尿病对宫内生长受限大鼠成年后心肌胶原沉积和心功能的影响。
通过限制妊娠母鼠的蛋白质摄入诱导 IUGR。当后代 24 周龄时，通过链脲佐菌素诱导 IUGR 和非 IUGR 雄性大鼠发生糖尿病；使用胰岛素注射将血糖水平维持在轻度（7-10mmol/L；每组 8 只）或中度水平（10-15mmol/L；每组 8 只）。当大鼠 32 周龄时，进行超声心动图和心脏形态分析。
IUGR 后代在 32 周时表现出心肌肥厚，包括左心室后壁增厚和间质纤维化增加。高血糖导致心脏增大和心肌纤维化增加。IUGR 和非 IUGR 大鼠对高血糖的反应没有差异；然而，当糖尿病与 IUGR 病史同时存在时，心脏纤维化最为严重。一般来说，将血糖水平维持在轻度高血糖水平可减轻高血糖的不良影响，但不能逆转纤维化。
高血糖状态下 IUGR 后代的纤维化加重可能导致长期的心脏功能障碍。
