Franco Maria do Carmo, Ponzio Beatriz Felice, Gomes Guiomar Nascimento, Gil Frida Zaladek, Tostes Rita, Carvalho Maria Helena Catelli, Fortes Zuleica Bruno
Federal University of São Paulo - Nephrology Division - Medicine Department, R. Botucatu, 740 - São Paulo, SP 04023-900, Brazil.
Life Sci. 2009 Aug 12;85(7-8):327-33. doi: 10.1016/j.lfs.2009.06.013. Epub 2009 Jul 2.
The premise that intrauterine malnutrition plays an important role in the development of cardiovascular and renal diseases implies that these disorders can be programmed during fetal life. Here, we analyzed the hypothesis that supplementation with mixed antioxidant vitamins and essential mineral in early life could prevent later elevation of blood pressure and vascular and renal dysfunction associated with intrauterine malnutrition.
For this, female Wistar rats were randomly divided into three groups on day 1 of pregnancy: control fed standard chow ad libitum; restricted group fed 50% of the ad libitum intake and a restricted plus micronutrient cocktail group treated daily with a combination of micronutrient (selenium, folate, vitamin C and vitamin E) by oral gavage.
In adult offspring, renal function and glomerular number were impaired by intrauterine malnutrition, and the prenatal micronutrient treatment did not prevent it. However, increased blood pressure and reduced endothelium-dependent vasodilation were prevented by the micronutrient prenatal treatment. Intrauterine malnutrition also led to reduced NO production associated with increased superoxide generation, and these parameters were fully normalized by this prenatal treatment.
Our current findings indicate that programming alterations during fetal life can be prevented by interventions during the prenatal period, and that disturbance in availability of both antioxidant vitamins and mineral may play a crucial role in determining the occurrence of long-term cardiovascular injury.
宫内营养不良在心血管疾病和肾脏疾病的发生发展中起重要作用这一前提意味着这些疾病可能在胎儿期就被编程。在此，我们分析了早期补充混合抗氧化维生素和必需矿物质可预防与宫内营养不良相关的后期血压升高以及血管和肾功能障碍这一假设。
为此，在妊娠第1天，将雌性Wistar大鼠随机分为三组：自由摄食标准饲料的对照组；摄食量限制在自由摄食水平50%的限制组；以及通过口服灌胃每日接受微量营养素（硒、叶酸、维生素C和维生素E）组合治疗的限制加微量营养素鸡尾酒组。
在成年后代中，宫内营养不良损害了肾功能和肾小球数量，产前微量营养素治疗未能预防这种情况。然而，微量营养素产前治疗预防了血压升高和内皮依赖性血管舒张功能降低。宫内营养不良还导致与超氧化物生成增加相关的一氧化氮生成减少，而这种产前治疗使这些参数完全恢复正常。
我们目前的研究结果表明，胎儿期的编程改变可通过产前干预来预防，抗氧化维生素和矿物质供应的紊乱可能在决定长期心血管损伤的发生中起关键作用。
