Maternal supplementation of diabetic mice with thymoquinone protects their offspring from abnormal obesity and diabetes by modulating their lipid profile and free radical production and restoring lymphocyte proliferation via PI3K/AKT signaling.

Maternal supplementation of diabetic mice with thymoquinone protects their offspring from abnormal obesity and diabetes by modulating their lipid profile and free radical production and restoring lymphocyte proliferation via PI3K/AKT signaling.
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DOI:
10.1186/1476-511x-12-37
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发表时间:
2013-03-18
影响因子:
4.5
通讯作者:
Rabah DM
Rabah DM
中科院分区:
医学3区
文献类型:
--
作者:
Badr G;Mahmoud MH;Farhat K;Waly H;Al-Abdin OZ;Rabah DM

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流行病学研究表明,在怀孕期间患有糖尿病的母亲的后代患健康并发症的可能性是在怀孕期间没有患糖尿病的母亲的后代的七倍。本研究旨在探讨是否补充链脲佐菌素(STZ)诱导的糖尿病妊娠小鼠与胸腺醌(TQ)在妊娠期和哺乳期改善其后代获得的糖尿病并发症的风险。使用三组妊娠雌性小鼠:非糖尿病对照母鼠(CD)、糖尿病母鼠(DD)和妊娠期和哺乳期补充TQ的糖尿病母鼠(DD + TQ)(每组n = 10只雌性小鼠)。我们的数据表明,出生DD的新生儿数量显着减少,这些新生儿显示出显着增加,他们的平均体重(巨大的幼崽)相比,出生CD和DD + TQ。在妊娠和哺乳期间诱导糖尿病导致巨大幼崽出现几种产后并发症,如血糖、自由基、血浆促炎细胞因子(IL-1β、IL-6和TNF-α)和脂质水平显著升高,以及与CD后代相比有异常肥胖的趋势。相比之下,DD所生的巨体后代表现出血浆细胞因子水平(IL-2、IL-4和IL-7)显著降低,循环淋巴细胞数量明显减少,超抗原(SEB)刺激的淋巴细胞增殖减少,AKT磷酸化异常。在妊娠期和哺乳期补充DD和TQ对新生儿的数量和平均体重有明显的影响。此外,TQ显着恢复血糖,胰岛素,自由基,血浆细胞因子和脂质水平,以及淋巴细胞增殖的后代。我们的数据表明,营养补充DD与天然抗氧化剂TQ在怀孕和哺乳期保护他们的后代从发展糖尿病并发症,并保留了有效的淋巴细胞免疫反应以后的生活。
Epidemiological studies have shown that the offspring of mothers who experience diabetes mellitus during pregnancy are seven times more likely to develop health complications than the offspring of mothers who do not suffer from diabetes during pregnancy. The present study was designed to investigate whether supplementation of streptozotocin (STZ)-induced diabetic pregnant mice with thymoquinone (TQ) during pregnancy and lactation improves the risk of developing diabetic complications acquired by their offspring. Three groups of pregnant female mice were used: non-diabetic control dams (CD), diabetic dams (DD), and diabetic dams supplemented with TQ (DD + TQ) during pregnancy and lactation (n = 10 female mice in each group). Our data demonstrated a marked decrease in the number of neonates born to DD, and these neonates showed a marked increase in their mean body weight (macrosomic pups) compared to those born to CD and DD + TQ. The induction of diabetes during pregnancy and lactation resulted in macrosomic pups with several postpartum complications, such as a marked increase in their levels of blood glucose, free radicals, plasma pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α), and lipids, and a tendency toward abnormal obesity compared to the offspring of CD. By contrast, macrosomic offspring born to DD exhibited a marked reduction in plasma cytokine levels (IL-2, -4 and -7), an obvious reduction in the number of circulating lymphocytes, decreased proliferation of superantigen (SEB)-stimulated lymphocytes and aberrant AKT phosphorylation. Interestingly, the supplementation of DD with TQ during pregnancy and lactation had an obvious and significant effect on the number and mean body weight of neonates. Furthermore, TQ significantly restored the levels of blood glucose, insulin, free radicals, plasma cytokines, and lipids as well as lymphocyte proliferation in the offspring. Our data suggest that the nutritional supplementation of DD with the natural antioxidant TQ during pregnancy and lactation protects their offspring from developing diabetic complications and preserves an efficient lymphocyte immune response later in life.