Elmes Matthew J, Gardner David S, Langley-Evans Simon C
Division of Nutritional Sciences, University of Nottingham, Sutton Bonington Campus, Loughborough, Leicestershire, UK.
Br J Nutr. 2007 Jul;98(1):93-100. doi: 10.1017/S000711450769182X. Epub 2007 Apr 20.
Rats exposed to protein restriction as fetuses develop hypertension as adults. Hypertension increases the risk of myocardial ischaemia and infarction. We investigated whether rats exposed to low-protein diets in utero are more susceptible to myocardial ischaemia-reperfusion (IR) injury. Pregnant Wistar rats were fed control or low-protein (MLP) diets throughout pregnancy. At 4 and 8 weeks postnatal age systolic blood pressure was determined in the offspring using tail-cuff plethysmography. At 6 months of age, rats were treated with saline or N-acetylcysteine (NAC) for 48 h. Rapidly excised hearts were retro-perfused (Langendorff) to assess isolated cardiac function before (baseline), during 30 min ischaemia (no coronary perfusion) and for 60 min after reinstating coronary perfusion (reperfusion). Hearts were then harvested and treated appropriately for analysis of infarct size. Exposure to the MLP diet in utero significantly increased systolic blood pressure at 4 and 8 weeks of age (6-13 mmHg increase; P < 0.001) and significantly impaired recovery of left ventricular developed pressure after ischaemia at 6 months of age in male offspring only (P < 0.003). Pre-treatment with NAC prevented this impairment of recovery in MLP male offspring and improved recovery in all females. Myocardial infarct size was not different between dietary groups after IR, but NAC pre-treatment significantly reduced the degree of infarction (P < 0.001). In conclusion, an MLP diet throughout gestation significantly impairs recovery of the 6-month-old adult rat heart to IR-induced injury in a sex-specific manner. Undernutrition during development may increase susceptibility to CHD by impairing recovery from coronary events.
胎儿期蛋白质摄入受限的大鼠成年后会患高血压。高血压会增加心肌缺血和梗死的风险。我们研究了子宫内暴露于低蛋白饮食的大鼠是否更容易受到心肌缺血再灌注(IR)损伤。妊娠期间,将怀孕的Wistar大鼠喂食对照饮食或低蛋白(MLP)饮食。在出生后4周和8周龄时,使用尾袖体积描记法测定后代的收缩压。在6个月大时,大鼠用生理盐水或N-乙酰半胱氨酸(NAC)处理48小时。快速切除心脏后进行逆行灌注(Langendorff),以评估在缺血前(基线)、缺血30分钟(无冠状动脉灌注)期间和恢复冠状动脉灌注后60分钟(再灌注)的离体心脏功能。然后收获心脏并进行适当处理以分析梗死面积。子宫内暴露于MLP饮食会显著增加4周和8周龄时的收缩压(升高6-13 mmHg;P<0.001),并且仅在雄性后代6个月大时缺血后显著损害左心室舒张末压的恢复(P<0.003)。NAC预处理可防止MLP雄性后代的这种恢复受损,并改善所有雌性的恢复。IR后饮食组之间的心肌梗死面积没有差异,但NAC预处理显著降低了梗死程度(P<0.001)。总之,整个妊娠期的MLP饮食会以性别特异性方式显著损害6个月大成年大鼠心脏对IR诱导损伤的恢复。发育期间的营养不良可能会通过损害冠状动脉事件后的恢复而增加患冠心病的易感性。