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链脲佐菌素诱导的母体子宫内高血糖环境及其对大鼠高出生体重成年后代发育和代谢的影响

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

作者信息

Li Xin, Luo Shu-jing, Zhang Kai, Yang Hui-xia

机构信息

Department of Obstetries and Gynecology, Peking University First Hospital, Beijing 100034, China.

出版信息

Zhonghua Fu Chan Ke Za Zhi. 2012 Oct;47(10):769-76.

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 increased 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.

摘要

目的

建立并评估链脲佐菌素诱导的糖尿病大鼠高出生体重后代模型,以及这些后代母体高血糖的长期代谢影响。

方法

将链脲佐菌素(STZ,25mg/kg)一次性腹腔注射给Wistar大鼠(G组,n = 14)以诱导母体高血糖模型(血糖在10 - 20mmol/L之间),另有若干大鼠定义为严重高血糖模型组(SG组,n = 5)。对照组(C组,n = 7)给予相同体积的柠檬酸盐缓冲溶液。记录体重和血糖,并在妊娠期用血糖仪进行灌胃葡萄糖耐量试验(LGTT)。将后代相应分为2组,并记录出生体重。观察所有后代的体重、血糖、血压(仅雄性大鼠)等。

结果

(1)模型建立5天后,G组(16.8±5.4mmol/L)和SG组(20.5±5.6mmol/L)的血糖与C组(7.0±1.4mmol/L)相比显著升高(P < 0.01);与C组(5.8±1.1mmol/L)相比,G组(16.6±3.4mmol/L)和SG组(23.8±1.5mmol/L)的平均血糖也升高,差异有统计学意义(P < 0.01)。(2)根据在第4天和第10天进行的LGTT结果,G组每个时间点的血糖与C组相比显著升高(P < 0.01)。(3)G组的雄性和雌性出生体重显著高于C组和SG组(P < 0.05),SG/G/C组的血糖分别为(6.5±1.2)mmol/L、(4.1±0.8)mmol/L、(4.1±0.8)mmol/L,根据统计结果,SG组与G/C组之间的差异均显著(P < 0.05)。(4)哺乳期后,C组母鼠的体重、李氏指数、脂肪重量及脂肪重量占比与SG组相比呈下降趋势(P < 0.05),G组与SG组相比也是如此(P < 0.05)。(5)在G组雌性后代中,出生体重与C组相比显著增加(P < 0.05);自12周起,雌性后代的体重与C组相比呈增加趋势,但无统计学意义;自15周起,G组与C组之间的体重有显著差异(P < 0.05),且该趋势持续至26周;在G组雄性后代中,出生日和4周时的体重与C组相比有显著升高(P < 0.05);从那时起,雄性后代的体重与C组相比呈增加趋势,但直到26周才有统计学意义(P > 0.05)。(6)在G组中,自20周起,雌性后代LGTT 30分钟和60分钟时的血糖高于C组(P < 0.05);LGTT(30分钟)的血糖直到24周仍有显著升高(P < 0.05);在G组中,自16周起,雄性后代LGTT 30分钟时的血糖显著高于C组(P < 0.05);LGTT(30分钟)的血糖直到24周仍有显著升高(P < 0.05)。(7)G组雄性后代在12周时的血压与C组相比有显著升高(P < 0.05);从那时起,G组的血压持续上升趋势直到26周,但无统计学意义(P > 0.05)。

结论

妊娠第1天一次性腹腔注射STZ(25mg/kg)可复制糖尿病高出生体重大鼠模型,观察到体重有明显代谢变化、葡萄糖耐量和血压。这些结果可能是人类妊娠期糖尿病及其巨大儿临床研究的一个进步,这些巨大儿在以后的生活中可能患某些代谢疾病。

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