Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats
Dietary polyunsaturated fatty acid prevents malformations in offspring of diabetic rats
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DOI：
10.1016/s0002-9378(96)80005-6
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发表时间：
1996-10-01
影响因子：
9.8
通讯作者：
Sloskey, G
中科院分区：
文献类型：
--
作者：
Reece, EA;Wu, YK;Sloskey, G
目的：探讨膳食来源花生四烯酸是否可以作为药物预防高血糖的致畸作用。研究设计：80d龄SD大鼠交配，受孕后随机分为5组：2组为非糖尿病正常对照组，3组为链脲佐菌素实验性糖尿病组。在两组对照组中，一组喂以正常饮食(组1)，另一组(组2)喂食普通饮食和1.0毫升红花油，红花油是一种多不饱和仙人酸，可提高血清花生四烯酸水平。在三个糖尿病组(组3、4和5)中，通过停止每日胰岛素治疗，允许血糖水平保持在>；350 mg/dl。第3组：正常饮食不补充；第4组：正常饮食+生理盐水假喂；第5组：普通饮食+红花油1.0ml。结果：未接受胰岛素治疗和正常饮食的糖尿病大鼠的子代畸形率为20%，对照组为4.8%。对照组口服补充生理盐水或红花油不会改变生长或畸形率。在接受口服生理盐水补充的糖尿病大鼠中，这些比率同样没有受到影响。然而，对糖尿病大鼠补充红花油后，神经管畸形的发生率从20.0%下降到7.6%(p<；0.0001)。畸形率与血清花生四烯酸水平呈负相关：非糖尿病对照组为17.83(SD 5.84 mU g/m l)，畸形率为4.8%；糖尿病组为14.18(SD 2.58 m u g/m l)，畸形率为20.0%(p<；0.05)。补充红花油后，血清花生四烯酸水平从14.18+/-2.58 mU/ml增加到19.99+/-7.99 mU/g/ml(p<；0.05)；这与畸形率的下降有关。结论：这些数据表明糖尿病胚胎病变与必需脂肪酸缺乏有关，这证实了我们之前的体外研究结果，此外，饮食中使用一种特异性增加花生四烯酸水平的多不饱和脂肪酸显著降低了糖尿病胚胎病变的发生率。这些发现可作为开发药物预防糖尿病所致先天畸形的策略的基础。
OBJECTIVE: The purpose of the current study was to determine whether a dietary source of arachidonic acid could serve as a pharmacologic prophylaxis to obviate the teratogenic effects of hyperglycemia.STUDY DESIGN: Eighty-day-old Sprague-Dawley rats were mated, and after conception were randomly allocated to five groups: two groups were nondiabetic normal controls and three groups had diabetes experimentally induced with streptozocin. Of the two control groups, one was fed a normal diet (group 1) and the other group (group 2) received a normal diet and 1.0 ml of safflower oil, a polyunsaturated fairy acid known to increase serum arachidonic acid levels, In the three diabetic groups (groups 3, 4, and 5) glucose levels were allowed to remain >350 mg/dl by withholding daily insulin therapy. Group 3 received a normal diet without supplementation; group 4 received a normal diet plus normal saline solution sham feedings, whereas group 5 received a normal diet supplemented with 1.0 ml of safflower oil. The oral agents (normal saline solution and polyunsaturated fatty acid) were administered with a tuberculin syringe.RESULTS: Diabetic rats not receiving insulin therapy and receiving normal diets produced offspring with malformation rates of 20% compared with control rates of 4.8%. Supplemental normal saline solution or safflower oil given orally to controls did not alter the growth or malformation rates. These rates were similarly unaffected in the diabetic rats receiving oral supplementation of normal saline solution. However, with safflower oil supplementation to diabetic rats the incidence of neural tube defects was decreased from 20.0% to 7.6% (p < 0.0001). An inverse relationship was observed between the malformation rate and the serum arachidonic acid level: 17.83 (SD 5.84 mu g/ml) in the nondiabetic controls, with a malformation rate of 4.8%, versus 14.18 (SD 2.58 mu g/ml) in the diabetic rats, with a malformation rate of 20.0% (p < 0.05). With safflower oil supplementation serum levels of arachidonic increased from 14.18 +/- 2.58 mu g/ml to 19.99 +/- 7.99 mu g/ml (p < 0.05); this was associated with a concomitant decline in the malformation rate.CONCLUSION: These data demonstrate that diabetic embryopathy is associated with a deficiency state in essential fatty acid, corroborating our previous in vitro findings, Furthermore, the use of a dietary polyunsaturated fatty acid that specifically increases arachidonic levels significantly reduced the incidence of diabetic embryopathy. These findings may serve as a basis for developing strategies of pharmacologic prophylaxis against diabetes-induced congenital malformations.