建立大鼠代谢综合征模型及其胎盘和成年个体中糖脂代谢性别差异研究  

Establishment of the rat model of metabolic syndrome and study of gender differences in glucose and lipid metabolism in placenta and adult individuals

作　　者：姚灿灿 刁天 吕志远 徐祥波 陈西华 贺斌 YAO Can-can;DIAO Tian;L Zhi-yuan;XU Xiang-bo;CHEN Xi-hua;HE Bin(National Research Institute for Family Planning,NHC Key Laboratory of Reproductive Health Engineering&Technology Research Center,Beijing 100081;Graduate School,Peking Union Medical College,Beijing 100730;Academy for Advanced Interdisciplinary Studies,Peking University,Beijing 100871)

机构地区：[1]国家卫生健康委科学技术研究所,国家卫生健康委员会生殖健康工程技术研究中心,北京100081 [2]北京协和医学院研究生院,北京100730 [3]北京大学前沿交叉学科研究院,北京100871

出　　处：《生殖医学杂志》2024年第6期763-774,共12页Journal of Reproductive Medicine

基　　金：中国医学科学院医学与健康科技创新工程项目(2018-I2M-1-004)。

摘　　要：目的构建代谢综合征实验动物模型并探究糖脂代谢异常在胎盘和成年个体的雌雄差异。方法采用高热量饮食+5%果糖饮水诱导大鼠妊娠期代谢综合征(GMS)模型。雌性大鼠GMS模型及妊娠:16只雌性Wistar大鼠随机分为对照组(正常饮食饮水+妊娠;NC组,n=8)和GMS模型组(高热量饮食+5%果糖饮水+妊娠;HDF5组,n=8)。雄性及雌性大鼠代谢综合征(MS)模型:雌、雄性大鼠各14只分别随机分为2组,即雌性大鼠MS组(F-HDF5组,n=7)、雄性大鼠MS组(M-HDF5组,n=7),雌、雄性大鼠对照组(F-NC组,n=7;M-NC组,n=7)。分别在适应1周后的基线时(W0)到饮食/饮水干预第5周(W5)内每周监测记录各组大鼠的体重、收缩压(SBP)和舒张压(DBP),于W0和W5检测其空腹血糖(FBG)值并进行口服葡萄糖糖耐量试验(OGTT),并采集空腹血清检测甘油三酯(TGs)和总胆固醇(T-CHO)浓度。在W5时收集各组大鼠的空腹血清和肝脏组织,于妊娠第20.5天(GD20.5)收集胎鼠及胎盘组织,检测胎盘组织TGs和T-CHO浓度、脂蛋白脂肪酶(LPL)活性和游离脂肪酸(FFA)含量以及胎盘组织HE和油红O染色。结果(1)在经饮食/饮水干预5周后,相较于NC组,HDF5组的体重(P<0.001)和BMI(P<0.05)、FBG(P<0.001)和OGTT血糖变化曲线下面积(AUC)(P<0.05)、TGs和T-CHO(P<0.001)、SBP(P<0.001)和DBP(P<0.05)的指标均显著升高,提示成功构建雌性大鼠GMS模型,且妊娠期血压升高(P<0.05);与NC组比较,GD20.5时HDF5组FBG、TGs和T-CHO均显著增加(P<0.001),雄性胎盘重量显著增加(P<0.01),雌雄性胎盘LPL活性均显著降低(P<0.01),TGs、T-CHO、FFA含量显著增加(P<0.05)且雄性胎盘中的含量及脂滴显著高于雌性胎盘(P<0.05)。(2)在成年的雌雄大鼠MS模型中,经5周干预后,相较于M-NC组,M-HDF5的BMI无显著增加(P>0.05),而其余各项与MS相关的指标在F-HDF5组和M-HDF5组均显著升高(P<0.05),F-HDF5组以血糖升高更为显著(P<0.05),而M-HDF5组以血脂升高更为显著(P<0.001);两组大鼠肝�Objective:To construct an experimental animal model of metabolic syndrome(MS)and to explore the sexual dimorphism of glucose and lipid metabolism abnormalities in both placenta and adult individuals.Methods:The rat model of gestational metabolic syndrome(GMS)was induced by a high-calorie diet plus 5%fructose water.Sixteen female Wistar rats were randomly divided into two groups as the control group(normal diet and water,NC group,n=8)and GMS group(high-calorie diet and 5%fructose drinking water,HDF5 group,n=8).And there are 14 female rats and 14 male rats were randomly and respectively divided into two groups as female MS group(F-HDF5 group,n=7),male MS group(M-HDF5 group,n=7),and both control groups with normal diet and water intake(F-NC group,n=7,M-NC group,n=7).The body weight(weight),systolic blood pressure(SBP)and diastolic blood pressure(DBP)of the rats in each group were monitored and recorded weekly from baseline(W0)after 1 week of adaptation to the 5 th week of diet/water intervention(W5).Fasting blood glucose(FBG)levels were detected on W0 and W5,and oral glucose tolerance test(OGTT)was performed.Fasting serum was collected for detection of triglyceride(TGs)and total cholesterol(T-CHO)concentrations.Fasting serum and liver tissues of male and female MS rat models were collected in W5,and fetal mice and placenta tissues were collected at 20.5 days of gestation(GD20.5),and concentrations of TGs and T-CHO,lipoprotein lipase(LPL)activity and free fatty acid(FFA)content of placenta tissues were detected.The placenta tissues were subjected to HE staining and Oil Red O staining.Results:After 5 weeks of diet/water intervention,the measured values of body weight(P<0.001)and body mass index(BMI,P<0.05),FBG(P<0.001)and the area under the receiver operating characteristic curve(AUC,P<0.05),TGs and T-CHO(P<0.001),SBP(P<0.001)and DBP(P<0.05)in the HDF5 group were significantly increased,suggesting that the female rat GMS model was successfully constructed,and the blood pressure was increased during pregnancy(P<0.05).A

关 键 词：妊娠期代谢综合征 糖脂代谢异常 性别差异 建模方法 

分 类 号：R715.3[医药卫生—妇产科学] R714.7[医药卫生—临床医学]