妊娠期糖尿病母鼠之新生小鼠海马组织形态变化及基因差异表达的观察  

Observation of morphological changes and differential gene expression in hippocampus of neonatal mice given birth by gestational diabetes mellitus mother mice

作　　者：黄婉仪[1] 张又祥[1] 王丽娜[1] 罗梅娟[1] 刘瑜华 胡家奇 HUANG Wan-yi;ZHANG You-xiang;WANG Li-na;LUO Mei-juan;LIU Yu-hua;HU Jia-qi(Department of Pediatrics,Guangzhou First People's Hospital,Guangzhou 510180,Guangdong,China)

机构地区：[1]广州市第一人民医院儿科,广东广州510180

出　　处：《广东医学》2023年第3期271-277,共7页Guangdong Medical Journal

基　　金：广州市卫生健康科技西医类一般引导项目(20201A011003)。

摘　　要：目的观察妊娠期糖尿病孕鼠致新生小鼠海马组织形态结构异常及其海马组织基因差异的表达。方法雌鼠随机分为GDM组(9只)和对照组(9只),然后将GDM组分为A组和C组,对照组分为B组和D组。GDM组建立妊娠期糖尿病孕鼠模型,并取其子鼠海马组织,一部分组织进行病理切片并采用HE染色法观察GDM组新生鼠海马组织形态结构的变化;另外一部分海马组织采用基因芯片技术筛选出妊娠期糖尿病母鼠之子代小鼠海马组织差异表达基因。结果(1)一次性腹腔注射干预次日起,与对照组相比,GDM组空腹血糖较高,两组差异有统计学意义(P<0.05);在干预的第3天后,发现GDM组孕鼠随机血糖较对照组高,差异有统计学意义(P<0.05);进一步的分析可知,自E4.5(妊娠早期)起,GDM组孕鼠随机血糖迅速上升至成模水平(≥11.1 mmol/L),并持续上升。(2)两组海马组织进行病理切片及HE染色,经观察发现,对照组小鼠海马细胞形态饱满完整;GDM组小鼠海马组织CA3区细胞排列紊乱,形态欠规则。(3)采用基因芯片方法检测糖尿病母鼠所生小鼠海马组织中差异表达,结果显示,组织中下调miRNA 11个,无上调miRNA。筛选出miRNA-3473b,运用q-PCR技术验证了其表达下调(P<0.05)。结论miRNA-3473b可能参与了妊娠期高血糖对子代小鼠的神经系统发育的负向影响作用,导致其出现学习、认知能力的下降。初步揭示妊娠期高血糖对子代神经系统发育影响的分子学机制。Objective To observe the abnormal morphology and structure and differential gene expression of hippocampal tissue in neonatal mice given birth by pregnant mice with gestational diabetes mellitus(GDM).Methods A GDM pregnant mouse model was established,and hippocampal tissue was collected from its offspring.Pathological sections of part of the tissue were used to observe the morphological and structural changes of hippocampal tissue in neonatal mice of GDM group.In another part of the hippocampal tissue,differentially expressed genes were screened from the offspring of GDM female mice by gene chip technique,and their differential expression was verified by q-PCR.Results From the 2nd day(E1.5)after intraperitoneal injection of medicines,fasting blood glucose in GDM groups(Group A and C)was significantly higher than those in control groups(Group B and D)(P<0.05).Compared with the control groups,the random blood glucoses of pregnant mice in GDM groups(Group A and C)were significantly higher on the third day(D2.5)after intraperitoneal injection of medicines(P<0.05).Since D4.5(early pregnancy),the random blood glucose of pregnant mice in GDM groups rapidly increased to the model level(≥11.1 mmol/L)and continued to rise.Pathological sections and HE staining of the hippocampal tissues of the two groups of newborn mice were conducted.Microscopic observation results showed that the hippocampal cells of mice in the normal control groups were full and complete in shape,arranged in an orderly manner and with clear structure.Compared with the control group,the cells in CA3 region of GDM groups were disordered with irregular morphology.Differential expression of miRNAs in the hippocampus of mice born by GDM mother mice was screened by gene chip,and 0 miRNA was up-regulated and 11 miRNAs were down-regulated.MiR-3473b was screened and its downregulated expression was verified by q-PCR(P<0.05).Conclusion MiR-3473b may be involved in the negative effects of hyperglycemia during pregnancy on the nervous system development of offspr

关 键 词：妊娠期糖尿病 子代小鼠 海马组织 miRNA-3473b 

分 类 号：R272.1[医药卫生—中医儿科学] R714.7[医药卫生—中医学]