The protective effect of zinc, selenium, and chromium on myocardial fibrosis in the offspring of rats with gestational diabetes mellitus
The protective effect of zinc, selenium, and chromium on myocardial fibrosis in the offspring of rats with gestational diabetes mellitus
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DOI：
10.1039/d2fo01105k
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发表时间：
2023-01-20
期刊：
影响因子：
6.1
通讯作者：
Yang, Xuefeng
中科院分区：
文献类型：
--
作者：
Deng, Haichao;Yao, Xueqiong;Yang, Xuefeng
妊娠期糖尿病(GDM)母亲的后代被认为有因宫内高血糖暴露而患心血管疾病的风险。我们先前的研究表明，锌、硒和铬显著减轻了GDM大鼠及其后代的葡萄糖耐量(P<；0.05)。然而，这些元素对妊娠期糖尿病子代心肌细胞损伤的影响及其可能的机制尚不清楚。在这里，我们研究了补充锌(每公斤体重10毫克)、硒(每公斤体重20微克)和铬(每公斤体重20毫克)对高脂蔗糖(HFS)饮食诱导的GDM大鼠子代心肌纤维化的有益影响。结果表明，不同日龄(3日龄、3周龄和成年期)GDM可引起子代大鼠的糖耐量异常、氧化应激、心脏炎症和心肌纤维化，补锌、补硒、补铬均能改善GDM的作用(P<；0.05)。添加营养素的GDM仔鼠心肌损伤标志物肌酸激酶同工酶(CK-MB)、乳酸脱氢酶(LDH)和天冬氨酸氨基转移酶(AST)活性较不添加营养素的仔鼠降低40~60%(P<；0.05)。此外，母鼠GDM诱导的纤维化相关蛋白的表达以及转化生长因子-β1(TGF-β1)/小母鼠抗十面瘫同系物3(SMAD3)信号通路在锌、硒和铬的补充下被下调(P<；0.05)。综上所述，锌、硒和铬可能通过抑制转化生长因子-β1/Smad3途径，在母体GDM诱导的子代从出生到成年期的心肌纤维化中起到保护作用。
The offspring of gestational diabetes mellitus (GDM) mothers are considered to be at the risk of cardiovascular diseases due to intrauterine hyperglycemia exposure. Our previous study showed that zinc, selenium, and chromium dramatically alleviated glucose intolerance in GDM rats and their offspring (P < 0.05). However, the effects of these elements on the damage of the cardiac myocytes of GDM offspring and the underlying mechanisms have not been demonstrated. Here, we investigated the beneficial effects of zinc (10 mg per kg bw), selenium (20 mu g per kg bw), and chromium (20 mu g per kg bw) supplementation on myocardial fibrosis in the offspring of GDM rats induced by a high-fat and sucrose (HFS) diet. The results showed that maternal GDM induced glucose intolerance, oxidative stress, cardiac inflammation and myocardial fibrosis in offspring rats during different ages (3 days, 3 weeks, and adulthood), which were ameliorated by zinc, selenium and chromium supplementation (P < 0.05). The activity of cardiac damage markers such as creatine kinase-myocardial band isoenzyme (CK-MB), lactate dehydrogenase (LDH) and aspartate aminotransferase (AST) decreased by 40-60% in element-supplemented offspring compared to that in non-supplemented offspring of GDM dams (P < 0.05). Moreover, maternal GDM-induced expression of fibrosis-related proteins and the transforming growth factor-beta 1 (TGF-beta 1)/small mothers against decapentaplegic homolog 3 (Smad3) signaling pathway in the heart tissue of offspring was down-regulated by zinc, selenium, and chromium supplementation (P < 0.05). In conclusion, zinc, selenium, and chromium may play a protective role in maternal GDM-induced myocardial fibrosis in offspring from birth to adulthood by inactivating the TGF-beta 1/Smad3 pathway.