早期研究已揭示高海拔地区孕妇、吸烟或患有妊娠糖尿病的孕妇子宫会供氧不足，使得胎儿得不到足够的氧气。虽然这些胎儿能在出生以前就适应了供氧不足的子宫环境，并且能存活下来，但低氧环境造成的伤害已经埋下疾病的诱因，婴儿到了成年期后罹患心血管疾病的风险会增高。

近日，发表在PLoS ONE杂志上的一项研究证实：当胎儿长期处于供氧不足的子宫环境下，胚胎心脏功能会发生变化，主动脉壁变厚，血液不易流动。引发心血管疾病的危险因素或许在婴儿出生之前就已经存在，研究人员认为孕妇子宫内缺氧环境可能对胎儿成长过程中心脏健康有损害。

该项研究的主要负责人英国剑桥大学生理学家Dino-Giussani认为孕妇子宫内氧气含量低的话，自由基的高活性反应分子会导致应激反应从而使胎儿心血管系统受到损害。

Dino-Giussani为了验证这一假说，设了4组妊娠大鼠，其中2组大鼠在低氧环境下饲养，2组正常对照组的大鼠在含氧量正常的环境下饲养。低氧环境下的老鼠放置于含氧量为13%的小室内，正常对照组老鼠放置于含氧量为21%的正常环境中。同时，一组低氧环境下饲养的老鼠以及一组正常对照组的老鼠每天给予含维生素C的水（维生素C具有抗氧化作用）。

结果发现那些未给予含维生素C的水组的低氧环境下饲养的孕鼠所生的幼鼠心脏主动脉壁明显增厚，超过正常组老鼠170%。而且，心脏氧化应激的信号分子如热休克蛋白等生物标记物含量也增多。大约4个月后，幼鼠成年时心脏博动的频率比正常环境下饲养的老鼠所生小鼠要快，但跳动很微弱。幼鼠的大动脉也容易出现阻塞现象，引发心血管疾病。但饮用含维生素C的水的低氧环境下饲养的孕鼠所生小鼠在未成年以及成年后，上述心血管疾病的症状却没有出现。

研究结果表明老鼠胎儿处于低氧环境下，孕鼠子宫受到氧化应激以致幼鼠在成年后心血管系统受到损害，但维生素C能有效地改善这一症状。

Dino-Giussani等人下一步研究重点将放在人类胚胎的需氧量水平上，尤其是考察那些生活在高海拔地区的妊娠妇女所生婴儿的心脏状况。

Developmental Programming of Cardiovascular Dysfunction by Prenatal Hypoxia and Oxidative Stress

Dino A. Giussani*, Emily J. Camm, Youguo Niu, Hans G. Richtera, Carlos E. Blancob, Rachel Gottschalk, E. Zachary Blake, Katy A. Horder, Avnesh S. Thakor, Jeremy A. et al.

Fetal hypoxia is a common complication of pregnancy. It has been shown to programme cardiac and endothelial dysfunction in the offspring in adult life. However, the mechanisms via which this occurs remain elusive, precluding the identification of potential therapy. Using an integrative approach at the isolated organ, cellular and molecular levels, we tested the hypothesis that oxidative stress in the fetal heart and vasculature underlies the molecular basis via which prenatal hypoxia programmes cardiovascular dysfunction in later life. In a longitudinal study, the effects of maternal treatment of hypoxic (13% O2) pregnancy with an antioxidant on the cardiovascular system of the offspring at the end of gestation and at adulthood were studied. On day 6 of pregnancy, rats (n = 20 per group) were exposed to normoxia or hypoxia ± vitamin C. At gestational day 20, tissues were collected from 1 male fetus per litter per group (n = 10). The remaining 10 litters per group were allowed to deliver. At 4 months, tissues from 1 male adult offspring per litter per group were either perfusion fixed, frozen, or dissected for isolated organ preparations. In the fetus, hypoxic pregnancy promoted aortic thickening with enhanced nitrotyrosine staining and an increase in cardiac HSP70 expression. By adulthood, offspring of hypoxic pregnancy had markedly impaired NO-dependent relaxation in femoral resistance arteries, and increased myocardial contractility with sympathetic dominance. Maternal vitamin C prevented these effects in fetal and adult offspring of hypoxic pregnancy. The data offer insight to mechanism and thereby possible targets for intervention against developmental origins of cardiac and peripheral vascular dysfunction in offspring of risky pregnancy.