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
作者:
作者单位:

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

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R-33


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

1. Department of Pediatric Surgery, Affiliated Hospital of North Sichuan Medical College, Nanchong 637000, China. 2. Institute of Hepatobiliary and Pancreaticoenteric Research, North Sichuan Medical College, Nanchong 637000

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    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。

    Abstract:

    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 GDM rats is feasible, and one intraperitoneal injection of 30 mg / kg STZ on day 1. 5 of gestation in SD rats safely and stably causes ureteral effusion (unilateral or bilateral) and renal dysplasia in offspring.

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欧阳辰昕,王 城,朱芮樟,廖君左,敬 鹏,何文飞,赵 丹.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[J].中国比较医学杂志,2022,32(10):32~39.

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  • 收稿日期:2022-04-27
  • 在线发布日期: 2023-05-08