1型糖尿病对小鼠早孕时期子宫肌层结构和细胞增殖的影响

Effects of type 1 diabetes on the muscularis structure and cell proliferation of uterine in mice during early pregnancy

目的 探讨1型糖尿病对小鼠早孕子宫肌层结构和细胞增殖的影响.方法 实验中共有7周龄Balb/C雌性小鼠73只,雄性小鼠20只.利用随机数字表法从雌性小鼠中随机取45只于尾静脉注射四氧嘧啶生理盐水溶液诱导1型糖尿病,其余28只作为对照组.共成功诱导1型糖尿病小鼠模型30只,根据随机数字表法选择28只作为糖尿病组.糖尿病组根据病程分为D1组（90～100 d）、D2组（101～ 110 d）.于孕168 h,取小鼠子宫肌层通过光镜、电镜下观察组织学病理变化;用免疫组织化学方法检测子宫肌层细胞增殖细胞核抗原（PCNA）的表达.建模前、后检测血糖、胰岛素;观察体重、饮水、饮食等.结果 成功构建了能自然交配并妊娠的糖尿病小鼠.与对照组相比,D1、D2组子宫内、外肌层细胞的增殖指数都明显降低（t=8.15,11.60,P均＜0.001）.同时,D1组全肌层厚度及内/外肌层间距均较对照组增大（t=2.12,4.40,P均＜0.05）,而D2组全肌层厚度及内/外肌层间距均较对照组明显减小（t=19.93,15.15,P均＜0.001）.D1组（t=2.25,3.46,P均＜0.05）、D2组（t=3.46,10.28,P均＜0.001）内、外肌层厚度较对照组减小.D1与D2组的内肌层和外肌层细胞的排列明显打乱.结论 糖尿病对小鼠早孕时期子宫肌层产生不良影响.

Objective To explore the effects of type 1 diabetes on uterine muscularis structure and cell proliferation in mice during early pregnancy.Methods There were 73 female and 20 male Balb/C mice at 7-week age in the test.Forty five female mice were selected according to random number table and injected with alloxan via tail vein to induce type 1 diabetes,and the remaining 28 mice were used as control group.Thirty type 1 diabetic mice were obtained,and 28 mice were selected according to random number table as diabetic group.Then all diabetic mice were divided into two group according to diabetic duration：D1 group （90-100 d） and D2 group （101-110 d） After pregnancy for 168 h,the changes of uterine muscle were examined by light microscope and electron microscope.Immunohistochemistry was used to detect the expression of proliferating cell nuclear antigen（PCNA） in myometrial cells.Blood glucose and insulin,water consumption,diet consumption,and weight were measured before and after the modeling.Results Natural mating and pregnant diabetic mice were successfully induced.Compared with control group,the cell proliferation of inner and outer muscular layer were significant decreased in D1 and D2 group（t =8.15-11.60,all P 〈 0.001）,the total thickness of the muscular layer,the spacing of inner and outer muscular layer were increased（t =2.12,4.40,all P 〈 0.05） in D1 group,while the total thickness of the musclar layer and the spacing of inner and outer muscular layer was significantly decreased in D2 group（t =19.93,15.15,all P 〈 0.001）.Compared with control group,the thickness of inner muscular layer and outer muscular layer were also decreased in D1 group （t =2.25,3.46,all P 〈 0.05） and D2 group （t =3.46,10.28,all P 〈 0.001）.And the ultrastructure of inner and outer muscular layer was also changed in D1 group and D2 group.Conclusion Diabetes could cause adverse effects to uterine muscular layer in early pregnant mice.