摘要
目的探讨妊娠糖尿病(GDM)孕鼠血清分泌型晚期糖基化终产物受体(sRAGE)对胎鼠发育的保护作用。方法以腹腔注射法建立SD孕鼠妊娠期糖尿病模型。随机将成功模型进行分组,分为实验及对照两组,对照组隔日尾静脉注射白蛋白溶液(5 mg/kg),实验组同时间点注射相同剂量的0.2 ml PBS稀释的重组sRAGE蛋白。第19天行剖宫产术,剥离胎盘,取出胚胎,记录胎鼠数量、体重、胎盘湿重,肉眼及病理观察胎鼠各系统器官发育畸形及缺陷情况,免疫组化显示子鼠脑、心脏组织切片中p65蛋白质入核状态,分析晚期糖基化终产物-糖基化终产物受体(AGEsRAGE)轴对妊娠期糖尿病孕鼠的胎鼠发育的保护作用。结果 (1)GDM孕鼠在子鼠的产子数量和胎盘湿重两项指标上与正常对照组差异不显著,但是GDM子鼠出现较高的子鼠发育异常和畸形,子鼠的平均体重也较对照组高(P<0.05),sRAGE处理可以降低子代发生畸形的概率,但子代畸形的概率与对照和GDM组相比仍然具有显著差异(P<0.05)。(2)GDM组孕鼠RAGE、EGFR、p65的mRNA表达呈明显上升,而经由sRAGE处理后,各项指标的mRNA表达逐渐下降接近于正常对照组的水平。(3)GDM组子鼠的脑、心脏组织切片后针对p65的免疫荧光染色显示,GDM组细胞中的p65被激活进入细胞核促进相关基因转录,而sRAGE处理显著抑制p65的入核。结论 GDM孕鼠的子代脑和心血管发育异常与孕鼠血清中AGEs水平以及组织中RAGE蛋白质表达水平显著相关,而AGEs-RAGE轴的调控平衡对子鼠发育和出生异常有显著的保护作用。
Objective To explore the protective effect of serum secretion type advanced glycation end product receptor on the development of fetal rats in gestational diabetic rats. Methods The intrauterine hyperglycemia model of SD pregnant rats were established by intraperitoneal injection. The successful models were randomly divided into experimental and control groups,rats in control group were given with intravenous injection of albumin solution（5 mg/kg）,at the same time rats in experimental group were injected with same dosage of 0. 2 ml PBS diluted recombinant sRAGE protein. In nineteenth day after cesarean section,placenta had been taken out,the number and weight of fetal rats were recorded,weight of placenta,gross and pathological observation of malformation and defect of fetal organs were carried out,immunohistochemical study showed that sections of fetal brain and heart tissue showed the condition of p65 protein into nucleus,and the protection rale of AGEs-RAGE axis in development of fetal rats in diabetic rats during pregnancy had been observed. Results（1）The difference in GDM in number of pregnant rats and birth weight of placenta in offspring in these two indexes and normal control group was not significant,but GDM group with higher abnormalities and malformations in offspring,and the average weight of offspring was higher than that of control group（P〈0.05）,sRAGE treatment can reduce the probability of deformity in offsprings. But the probability of malformation in offsprings compared with that of control group and GDM group has significant difference（P〈0.05）.（2）The expression levels of RAGE,EGFR and mRNA in GDM group were significantly increased,and the expression of mRNA was gradually decreased by sRAGE treatment,and its level was close to the level of normal control group.（3）The sections of brain and heart tissues in GDM group by immunofluorescence staining showed that GDM cells activate the p65 into the nucleus to promote gene transcription,while sRAGE treatment significantly inh
出处
《临床和实验医学杂志》
2017年第7期625-628,共4页
Journal of Clinical and Experimental Medicine
基金
广东省中医药局课题立项(编号:20142116)
