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目的探讨Toll样受体4(Toll-like receptor 4,TLR4)在编码sFlt-1的复制缺陷型重组腺病毒(adenoviral vector containing mouse full-length soluble fms-like tyrosine kinase 1,Adv-sFlt-1)诱导子痫前期小鼠模型临床特征中作用。方法构建Adv-sFlt-1子痫前期临床特征小鼠模型,观察TLR-4基因敲除对Adv-sFlt-1引起小鼠子痫前期临床特征的影响,酶联免疫吸附试验(Enzyme-linked immunosorbent assay,ELISA)测定孕鼠血浆可溶性fms样酪氨酸激-1(soluble fms-like tyrosine kinase 1,sFlt-1)含量,无创尾套法检测小鼠血压、双辛丁酸(bicinchoninic acid,BCA)法检测尿蛋白,肌酐检测试剂盒检测肌酐比值、苏木素-伊红(hematoxylin-eosin staining,HE)染色及透射电镜(transmission electron microscope,TEM)观察肾小球滤膜病理改变。结果 Adv-sFlt-1处理组血压、尿蛋白/肌酐比值明显高于正常对照组、空病毒处理组及TLR-4基因敲除Adv-sFlt-1处理组(P<0.05);Adv-sFlt-1处理组小鼠肾小球滤膜增厚,毛细血管内血栓形成、内皮细胞及足细胞发生病理改变,正常对照组、空病毒处理组及TLR-4基因敲除加Adv-sFlt-1处理组肾小球病理改变不明显。结论成功构建Adv-sFlt-1导致子痫前期临床特征小鼠模型,TLR4基因敲除可逆转AdvsFlt-1导致子痫前期小鼠模型的临床特征。TLR4可能在子痫前期病理过程中起重要作用。
Objective To investigate the role of Toll-like receptor 4 (TLR4) in the expression of sflt-1 adenoviral vector containing mouse full-length soluble fms-like tyrosine kinase 1 (Adv-sFlt-1) Induction of clinical features in preeclamptic mouse models. Methods The mouse model of Adv-sFlt-1 preeclampsia was constructed to observe the effect of TLR-4 knockout on the clinical features of Adv-sFlt-1-induced preeclampsia in mice. Enzyme-linked immunosorbent assay (ELISA) was used to measure the plasma soluble fms-like tyrosine kinase 1 (sFlt-1) in pregnant rats. The blood pressure, bicinchoninic acid (BCA) ) Method was used to detect urinary protein. The ratio of creatinine was detected by creatinine detection kit. The pathological changes of glomerular filtration membrane were observed by hematoxylin-eosin staining (HE) staining and transmission electron microscope (TEM). Results Adv-sFlt-1 treatment group was significantly higher than the control group, empty virus treatment group and TLR-4 knockout Adv-sFlt-1 treatment group (P <0.05); Adv-sFlt- 1 treatment group mice glomerular filtration membrane thickening, capillary thrombosis, endothelial cells and podocytes pathological changes, normal control group, empty virus treatment group and TLR-4 knockout plus Adv-sFlt-1 treatment Group glomerular pathological changes were not obvious. Conclusion The successful construction of Adv-sFlt-1 leads to a clinically characteristic mouse model of preeclampsia. TLR4 knockout can reverse the clinical characteristics of Advital-induced mouse model of preeclampsia. TLR4 may play an important role in the pathogenesis of preeclampsia.