硫酸普拉睾酮钠联合链脲佐菌素诱导大鼠PCOS伴2型糖尿病模型的实验研究

Animal Model of PCOS with Type 2 Diabetes Induced by Sodium Prasterone Sulfate and Streptozotocin

目的:研究采用硫酸普拉睾酮钠及高脂高糖饲料+链脲佐菌素(STZ)诱导PCOS伴2型糖尿病(2-DM)大鼠模型的实验方法。方法:将23日龄雌性SD大鼠分为PCOS组,PCOS伴2-DM组及对照组,PCOS组以硫酸普拉睾酮钠90μg(/g.d)皮下注射20 d,同时给予高脂高糖饲料喂养;PCOS伴2-DM组则在硫酸普拉睾酮钠停药后第2天给予STZ45 mg/kg腹腔注射1次,PCOS组及对照组注射等量柠檬酸盐缓冲液。注射后72 h处死大鼠,观察卵巢外观、光镜(HE染色)改变,测定血清睾酮(T)、雌二醇(E2)及血糖、胰岛素水平,计算HOMA-IR指数。结果:PCOS伴2-DM组与PCOS组大鼠卵巢均呈多囊样改变,血清T、E2浓度均显著高于对照组(P<0.01),PCOS伴2-DM组血糖浓度明显高于PCOS组及对照组(P<0.01),且HOMA-IR指数与对照组相比明显增高,差异有统计学意义(P<0.05)。结论:硫酸普拉睾酮钠联合高脂高糖饲料+低剂量STZ诱导SD幼年雌性大鼠的PCOS伴2-DM的动物模型,表现出与PCOS伴2-DM患者相似的内分泌特点,可用于PCOS远期并发症的研究,是较理想的动物模型。

Objective： To develop a rat model of polycystic ovarian syndrome（PCOS） with type 2 diabetes（2-DM） induced by sodium prasterone sulfate and streptozotocin（STZ）.Methods： Female rats aged 23-day were injected daily S.C.with sodium prasterone sulfate 90 μg/（g·d） for 20 days,then intraperitoneally injected streptozotocin once in a dose of 45 mg/kg.All rats were feed with high fat and sugar feed.The ovarian weight and pathological morphology was observed.The sera levels of testosterone（T）,estradiol（E2）,luteinizing hormone（LH）,follicle-stimulating hormone（FSH）,blood glucose（BG） and insulin（INS） were measured.Results： The ovaries of both PCOS group and the PCOS with 2-DM group showed multiple follicular cysts.Ovarian weight,sera T,E2 and INS of two groups were significantly higher than those of control group（P0.01）.BG concentration of the PCOS with 2-DM group was significantly higher than those of PCOS group and control group（P0.01）,while HOMA index of the PCOS with 2-DM group was higher that that of control group（P0.05）.Conclusions： The rat model of PCOS with 2-DM showed the morphologic and hormonal changes which were similar to patients with PCOS with 2-DM.This animal model induced by the sodium prasterone sulfate and streptozotocin is a good model of PCOS with 2-DM for studying the long-term complications of PCOS.