Streptozotocin-induced maternal intrauterine hyperglycemia environment and its influence on development and metabolic in adult offspring with high birth weight in rats

( views:371, downloads:0 )
Author:
LI Xin(Department of Obstetries and Gynecology, Peking University First Hospital,Beijing 100034, China)
LUO Shu-jing(Department of Obstetries and Gynecology, Peking University First Hospital,Beijing 100034, China)
ZHANG Kai(Department of Obstetries and Gynecology, Peking University First Hospital,Beijing 100034, China)
YANG Hui-xia(Department of Obstetries and Gynecology, Peking University First Hospital,Beijing 100034, China)
Journal Title:
Chinese Journal of Obstetrics and Gynecology
Issue:
Volume 47, Issue 10, 2012
DOI:
10.3760/cma.j.issn.0529-567x.2012.10.011
Key Word:
Diabetes mellitus, experimental; Diabetes, gestational ; Hyperglycemia; Fetal macrosomiat ; Growth ; Rats

Abstract: Objective To establish and assess the high-birth-weight offspring model of the diabetic rat induced by stueptozotocin,and the long-term metabolic impact of maternal hyperglycemia of those offsprings.Methods Streptozotocin (STZ,25 mg/kg) was given to Wistar rats (G group,n =14) once intraperitoneally to induce maternal hyperglycemia model (blood glucose between 10-20 mmol/L),and there still had a number of rats defined as severe hyperglycemia model group (SG group,n =5).The Control group (C group,n =7) were given the same volume citrate buffer solution.The body weight and blood glucose were recorded,and the lavaging glucose tolerance test (LGTT) was performed by a glucose meter in the gestation.The offsprings were corresponding allocated into 2 groups,and the birth weight were recorded.All the offsprings were observated body weight,blood glucose blood pressure (male rats only),and so on.Results (1) The blood glucose of G group (16.8 ±5.4 mmol/L) and SG group (20.5 ±5.6 mmol/L) were increased significantly as compared with C group (7.0 ± 1.4 mmol/L) 5 days after the model was established (P < 0.01) ; and the average blood glucose of G group (16.6 ± 3.4 mmol/L) and SG group (23.8 ± 1.5 mmol/L) increased too as comparede with C group (5.8 ± 1.1 mmol/L),the difference was significance according to statistics (P < 0.01).(2) According to the LGTT result,which operationed on generation day 4 and day 10,the blood glucose of every time point of G group were increased significantly as compared with C group (P < 0.01).(3) The male and female birth weight of G group was remarkably higher than the C group and the SG group (P < 0.05),and the blood glucose of SG /G/C group was (6.5 ±1.2) mmol/L,(4.1 ± 0.8) mmol/L,(4.1 ± 0.8) mmol/L respectively,according to the statistics results,the difference between SG group and G/C group respectively both remarkable (P < 0.05).(4) The body weight,Lee's index,fat weight,and the fat weight of mass ratio in C group mother rats after lactation presented dressed compared with the SG group (P < 0.05),and so as to the G group compared with the SG group (P < 0.05).(5) In the female offsprings of G group,the birth weight was remarkably increased compared with the C group (P < 0.05) ; the body weight of the female offsprings presented an increased trend compared with the C group since the 12 weeks,but had no statistical significance; there were significant differences of body weight between G group and C group since 15 weeks (P < 0.05),and the trend kept up until 26 weeks; in the male offsprings of G group,the body weight on birth day and 4 weeks had a marked rise compared with the C group (P < 0.05) ; and from then on,the body weight of the male offsprings presented an increased trend compared with the C group,but had no statistical significance until 26 weeks (P>0.05).(6) In G group,the blood glucose on 30 min and 60 min of LGTT in female offsprings were increased than the C group since 20 weeks (P < 0.05) ; the blood glucose of LGTT (30 min) still had a marked rise until 24 weeks (P < 0.05) ; in G group,the blood glucose on 30 min of LGTT in male offsprings was remarkably incrcascd than the C group since 16 weeks (P <0.05) ; the blood glucose of LGTT (30 min) still had a marked rise until 24 weeks (P < 0.05).(7) The blood pressure of male offsprings in G group had a marked rise on 12 weeks compared with the C group (P < 0.05) ; from then on the blood pressure of G group kept up a rise trend until 26 weeks,but had no statistical significance (P >0.05).Conclusion The diabetic high-birth-weight rat model could be duplicated with STZ (25 mg/kg) once intrapertoneally on the first day of gestation,which were observed some evidently metabolic changes in weight,glucose tolerance and blood pressure.These results could represent an forward step in the clinical study of human gestational diabetes mellitus and their macrosomia babies,which may suffer some metabolic disease in their later life.

  • [1]杨慧霞,孙伟杰,徐先明,等.WS 331-2011 妊娠期糖尿病诊断//中华人民共和国卫生行业标准.北京:中华人民共和国卫生部,2011.
  • [2]时春艳,杨慧霞,谢翠英,等.妊娠期糖代谢异常对巨大儿发生率及其他相关问题的影响.中华围产医学杂志,2005,8:9-12.
  • [3]毕晶珠,蒋文跃.筛选妊娠糖尿病巨大儿大鼠模型的新方法.中国比较医学杂志,2006,16:25-28.
  • [4]Wang Y,Campbell T,Perry B,et al.Hypoglycemic and insulinsensitizing effects of berberine in high-fat diet-and streptozotocin-induced diabetic rats.Metabolism,2011,60:298-305.
  • [5]柳国胜,罗瑶,赵立华,等.链脲霉素实验性大鼠妊娠糖尿病对子鼠心肌细胞超微结构的影响.暨南大学学报(医学版),2007,28:374-378.
  • [6]Ramkumar KM,Vijayakumar RS,Ponmanickam P,et al.Antihyperlipidaemic effect of Gymnema montanum:a study on lipid profile and fatty acid composition in experimental diabetes.Basic Clin Pharmacol Toxicol,2008,103:538-545.
  • [7]Parathath S,Grauer L,Huang LS,et al.Diabetes adversely affects macrophages during atherosclerotic plaque regression in mice.Diabetes,2011,60:1759-1769.
  • [8]Navaratna D,Guo SZ,Hayakawa K,et al.Decreased cerebrovascular brain derived neurotrophic factor mediated neuroprotection in the diabetic brain.Diabetes,2011,60:1789-1796.
  • [9]Segar EM,Norris AW,Yao JR,et al.Programming of growth,insulin resistance and vascular dysfunction in offspring of late gestation diabetic rats.Clin Sci (Lond),2009,117:129-138.
  • [10]秦佳佳,李瑞满.葛根素对妊娠期糖尿病大鼠胰岛素抵抗作用的研究.中药新药与临床药理,2008,19:89-91.
  • [11]Nasu R,Seki K,Nara M,et al.Effect of a high-fat diet on diabetic mother rats and their offspring through three generations.Endocr J,2007,54:563-569.
  • [12]Innes KE,Byers TE,Marshall JA,et al.Association of a woman's own birth weight with subsequent risk for gestational diabetes.JAMA,2002,287:2534-2541.
  • [13]Silverman BL,Metzger BE,Cho NH,et al.Impaired glucose tolerance in adolescent offspring of diabetic mothers.Relationship to fetal hyperinsulinism.Diabetes Care,1995,18:611-617.
  • [14]Hillier TA,Pedula KL,Schmidt MM,et al.Childhood obesity and metabolic imprinting:the ongoing effects of maternal hyperglycemia.Diabetes Care,2007,30:2287-2292.
  • [15]Van Assche FA,Holemans K,Aerts L.Long-term consequences for offspring of diabetes during pregnancy.Br Med Bull,2001,60:173-182.
  • [16]Soulimane-Mokhtari NA,Guermouche B,Saker M,et al.Serum lipoprotein composition,lecithin cholesterol acyltransferase and tissue lipase activities in pregnant diabetic rats and their offspring receiving enriched n-3 PUFA diet.Gen Physiol Biophys,2008,27:3-11.
  • [17]Khan NA.Role of lipids and fatty acids in macrosomic offspring of diabetic pregnancy.Cell Biochem Biophys,2007,48:79-88.
  • [18]Gillman MW,Oakey H,Baghurst PA.Effect of treatment of gestational diabetes on obesity in the next generation.Diabetes Care,2010,33:964-968.
WanfangData CO.,Ltd All Rights Reserved
About WanfangData | Contact US
Healthcare Department, Fuxing Road NO.15, Haidian District Beijing, 100038 P.R.China
Tel:+86-010-58882616 Fax:+86-010-58882615 Email:yiyao@wanfangdata.com.cn