链脲霉素致大鼠妊娠糖尿病影响子鼠发育的实验模型研究  

Animal model of streptozotocin induced gestational diabetes mellitus and its effect on fetal development

作　　者：柳国胜[1] 赵立华[1] 刘海英[1] 康举龄[2] 关洁宾[3] 罗先琼[4] 聂川[4] 

机构地区：[1]暨南大学附属第一医院儿科,广州510632 [2]暨南大学附属第一医院病理科,广州510632 [3]暨南大学附属第一医院动物实验中心,广州510632 [4]广东省妇幼保健院新生儿科

出　　处：《中国新生儿科杂志》2008年第1期26-30,F0003,共6页Chinese Journal of Neonatology

基　　金：广东省科技计划项目(2004B30701009号)

摘　　要：目的建立SD大鼠腹腔注射链脲霉素(STZ)致妊娠糖尿病的实验动物模型,为研究妊娠糖尿病对胎儿发育影响提供实验基础。方法将54只SD孕鼠随机分为STZ注射组(30只)和柠檬酸缓冲液注射对照组(24只),两组又按取材时孕龄不同随机分为第13、16天和19天3个亚组。对STZ注射组孕鼠,给予新配2%STZ溶液,按STZ40mg/kg,一次性腹腔注射,3d后空腹尾静脉采血监测血糖、尿糖和体重。对照组用同样方法注射等量的柠檬酸钠缓冲液。孕鼠于孕龄13、16、19d随机分批剖宫,观察完全流产、吸收胎、死胎及存活胎数等情况,检查子鼠的外部形态,测量子鼠体重。子鼠心脏切片经常规HE染色后,进行病理分析。结果STZ注射组孕鼠用药后出现"三多一少"现象,3d后血糖水平明显高于对照组(14.65±1.12)mmol/L比(3.06±0.39)mmol/L,t=48.29,P<0.01,尿糖均阳性,体重明显低于对照组(260.7±14.0)g比(273.7±16.7)g,t=3.11,P<0.01;13、16d和19d流产率均高于对照组,χ2分别为4.37、7.51和11.05,P<0.05;子鼠液化吸收胎、死胎、畸心胎例数较相应对照组高,χ2=77.21,P<0.01。STZ注射组子鼠心脏发育异常数较对照组多,F=196,P<0.01。结论该动物实验模型与人类妊娠糖尿病(GDM)拟合较好,且操作简便,重复性高,是研究妊娠糖尿病致胎儿发育异常较理想的实验模型。Objective To establish the animal model of gestational diabetes mellitus （ GDM ） induced by administering streptozotocin （STZ） intra-abdominally to provide an experimental basis for study of the effect of GDM on fetal development. Methods Fifty-four Sprague-Dawley pregnant rats were selected and randomly assigned into two groups, GDM group （n = 30） and control group （n =27 ）. The rats were injected with 2% STZ （40 mg/kg） or equal dosage of phosphate buffered saline （PBS） intraabdominally according to their assigned groups. Their blood glucose, urine glucose and body weights were measured 3 days later. The rats in each group were divided into three subgroups according to their gestational ages which were 13, 16 and 19 days. The rats in both groups underwent hysterectomy randomly to observe for complete abortion, absorbed fetus, demised fetus, live fetus, and morphorlogic examinations of the fetuses and weight of fetus at gestation age of 13, 16 and 19 days; their heart tissues were harvested for pathological study by HE staining. Results The pregnant rats of the GDM group showed significant signs of polyuria, polydipsia, hyperphagia and weight loss. It was observed that rats in GDM group had higher blood glucose level （ 14. 65 ± 1.12） mmol/L and （3.06 ± 0. 39） mmol/L respectively, t = 48.29, P 〈0. 01 ） ; their urine glucose was all positive and their weight was significantly less there that of the control group （260. 7 ± 14. 0） g and （273.7 ± 16. 7 ） g respectively, t = 3. 11, P 〈 0. 01 ）. The abortion rate in 13, 16 d and 19 d GDM group was higher than that of control group （χ^2 =4. 37, 7.51 and 11.05, P 〈 0. 05 ）. The incidences of fetal liquefaction and absorption, demised fetus, large fetus and fetal intrauterine growth retardation of GDM group were significantly higher than those of control group （χ^2 =77.21, P 〈0.01 ）. The incidence of heart defect of fetuses born to diabetic mothers was significantly higher than that of control group （F = 1

关 键 词：链脲菌素 糖尿病 妊娠 模型 动物 

分 类 号：R-332[医药卫生]