α-硫辛酸可减少糖尿病小鼠后代的先天性畸形。

Alpha-lipoic acid reduces congenital malformations in the offspring of diabetic mice.

作者信息

Sugimura Y, Murase T, Kobayashi K, Oyama K, Hayasaka S, Kanou Y, Oiso Y, Murata Y

机构信息

Department of Genetics, Research Institute of Environmental Medicine, Nagoya University, Furo-cho, Chikusa-ku, Nagoya, Japan.

出版信息

Diabetes Metab Res Rev. 2009 Mar;25(3):287-94. doi: 10.1002/dmrr.947.

DOI:10.1002/dmrr.947

PMID:19242917

Abstract

BACKGROUND

The mechanism of diabetes-induced congenital malformation remains to be elucidated. It has been reported that alpha-lipoic acid (LA) prevents neural tube defects (NTDs) in offsprings of rats with streptozotocin-induced diabetes. Here, we evaluate the protective effect of LA against diabetic embryopathy, including NTDs, cardiovascular malformations (CVMs), and skeletal malformations, in mice.

METHODS

Female mice were rendered hyperglycemic using streptozotocin and then mated with normal male mouse. Pregnant diabetic or non-diabetic mice were treated daily with either LA (100 mg/kg body weight) or saline between gestational days 0 and 18. On day 18, fetuses were examined for congenital malformations.

RESULTS

Plasma glucose levels on day 18 were not affected by LA treatment. No congenital malformations were observed either in the saline-treated or LA-treated non-diabetic group. In the saline-treated diabetic group, 39% of fetuses had external malformations and 30% had NTDs. In the LA-treated diabetic group, the corresponding proportions were 11 and 8%, respectively. LA treatment also decreased the incidence of CVMs from 30-3% and of skeletal malformations from 29-6%.

CONCLUSIONS

We conclude that LA can reduce NTDs, CVMs and skeletal malformations in the offspring of diabetic mice at term delivery.

摘要

背景

糖尿病诱发先天性畸形的机制仍有待阐明。据报道，α-硫辛酸（LA）可预防链脲佐菌素诱导的糖尿病大鼠后代的神经管缺陷（NTDs）。在此，我们评估LA对小鼠糖尿病胚胎病（包括NTDs、心血管畸形（CVMs）和骨骼畸形）的保护作用。

方法

使用链脲佐菌素使雌性小鼠血糖升高，然后与正常雄性小鼠交配。在妊娠第0天至18天期间，对怀孕的糖尿病或非糖尿病小鼠每天给予LA（100mg/kg体重）或生理盐水。在第18天，检查胎儿是否有先天性畸形。

结果

第18天的血浆葡萄糖水平不受LA治疗的影响。在生理盐水治疗组或LA治疗的非糖尿病组中均未观察到先天性畸形。在生理盐水治疗的糖尿病组中，39%的胎儿有外部畸形，30%有NTDs。在LA治疗的糖尿病组中，相应比例分别为11%和8%。LA治疗还使CVMs的发生率从30%降至3%，骨骼畸形的发生率从29%降至6%。