妊娠期糖尿病致子代先天性肾脏及尿路畸形大鼠模型的建立  

Establishment of a rat model of congenital abnormalities of the kidney and urinary tract in offspring due to gestational diabetes mellitus

作　　者：欧阳辰昕 王城[1,2] 朱芮樟[1,2] 廖君左 敬鹏[1] 何文飞[1] 赵丹[1,2] OUYANG Chenxin;WANG Cheng;ZHU Ruizhang;LIAO Junzuo;JING Peng;HE Wenfei;ZHAO Dan(Department of Pediatric Surgery,Affiliated Hospital of North Sichuan Medical College,Nanchong 637000,China;Institute of Hepatobiliary and Pancreaticoenteric Research,North Sichuan Medical College,Nanchong 637000)

机构地区：[1]川北医学院附属医院小儿外科,四川南充637000 [2]川北医学院肝胆胰肠研究所,四川南充637000

出　　处：《中国比较医学杂志》2022年第10期32-39,共8页Chinese Journal of Comparative Medicine

基　　金：四川省卫生健康委员会科研课题(20PJ147);南充市科技项目市校科技战略合作专项(19SXHZ0113)。

摘　　要：目的探索建立妊娠期糖尿病(GDM)致子代先天性肾脏及尿路畸形(CAKUT)SD大鼠模型的可行性。方法自然合笼受孕的SD大鼠孕鼠30只,于孕1.5 d一次性腹腔注射链脲佐菌素(STZ),据STZ浓度将孕鼠随机分为5组:STZ 30 mg/kg组、STZ 35 mg/kg组、STZ 40 mg/kg组、溶剂对照组(注射同剂量溶剂柠檬酸钠缓冲液)、空白对照组(不注射任何液体),每组6只,孕期监测孕鼠体重、血糖、流产情况。分娩第1天,记录子鼠存活率,解剖子鼠并观察泌尿系统畸形情况;子鼠横截面HE染色,多切面观察肾、输尿管异常情况,测量子鼠肾皮质厚度。结果STZ 30、35、40 mg/kg 3组子鼠均观察到输尿管扩张积水(双侧均达单侧3倍以上)及肾发育不良,输尿管总积水率均超70%,HE染色镜下表现为输尿管扩张积水、输尿管壁发育不良、肾实质变薄、肾皮质厚度降低(较空白对照组减少20%以上)。3组孕鼠血糖均达建模标准,其中STZ 30 mg/kg组血糖均值低于40 mg/kg组(P<0.05);STZ 35 mg/kg组血糖孕早期低于STZ 40 mg/kg组(P<0.05),在孕中晚期无差异(P>0.05)。仅STZ 40 mg/kg组孕鼠流产(流产率33.33%),3组子鼠存活率均低于空白对照组(P<0.05)。结论GDM大鼠子代CAKUT模型的建立具备可行性,SD大鼠孕1.5 d一次性腹腔注射STZ 30 mg/kg方案,能安全稳定地使子鼠发生输尿管积水(单侧或双侧)和肾发育不良。Objective To explore the feasibility of establishing a rat model of congenital abnormalities of the kidney and urinary tract(CAKUT)in offspring due to gestational diabetes mellitus(GDM).Methods Thirty naturally conceived SD rats were randomly divided into five groups by the concentration of streptozotocin(STZ)administered through a single intraperitoneal injection on day 1.5 of gestation:30 mg/kg STZ,35 mg/kg STZ,40 mg/kg STZ,solvent control(injected with the same dose of sodium citrate buffer),and blank control(not injected with any liquid)group(n=6 in each group).Weight,blood glucose and abortion of pregnant rats were monitored during pregnancy.On the first day of delivery,the survival rates of offspring were calculated.Offspring were dissected and assessed for abnormalities of the urinary tract.HE staining of cross-sections of the offspring was performed,and renal and ureteral abnormalities were observed and recorded in multiple sections.Renal cortical thickness was measured in offspring.Results Ureteral dilatation and effusion(bilateral up to more than three times of unilateral)and renal dysplasia were observed in 30,35 and 40 mg/kg STZ groups,and the total rates of ureteral effusion were>70%.HE staining revealed dilatation and effusion of the ureter,dysplasia of the ureteral wall,thinning of the renal parenchyma,and a reduction in the renal cortical thickness(more than 20% reduction compared with the blank control group).The blood glucose of all three groups reached the modeling standard,among which the mean blood glucose of the 30 mg/kg STZ group was lower than that of the 40 mg/kg STZ group(P<0.05).Blood glucose in the 35 mg/kg STZ group was lower than that in the 40 mg/kg STZ group during early pregnancy(P<0.05),and there was no difference during middle and late pregnancy(P>0.05).Only pregnant rats in the 40 mg/kg STZ group aborted(33.33% abortion rate),and survival rates in all three groups were lower than that in the blank control group(P<0.05).Conclusions Establishment of a CAKUT model in offspring of

关 键 词：妊娠期糖尿病 先天性肾脏及尿路畸形 链脲佐菌素 子代 大鼠 

分 类 号：R-33[医药卫生]