Preeclampsia-like glomerular lesions induced by a single injection of lipopolysaccharide (LPS) in pregnant rats

Abstract

Background. We induced pathological changes in the glomerular capillary walls by causing damage to endothelial cells produced by lipopolysaccharide (LPS) injection in pregnant rats and compared the induced lesions with those of human preeclamptic nephropathy, known as glomerular endothelial damage. Methods. Forty-three uninephrectomized and salt-loaded Wistar rats were divided into three groups. Twenty-six pregnant rats (Group I) and 9 nonpregnant rats (Group II) were injected intravenously with LPS (E. coli 055:B5, 130 µg/kg) on day 15 of gestation, and 8 pregnant rats (Group III) were injected with vehicle. The kidneys of the rats were pathologically and physiologically examined on day 20. Glomerular hemodynamic changes were evaluated under a real-time confocal laser-scanning microscope (CLSM) with a high-speed CCD video camera. Results. Twenty-one (81%) rats in Group I showed glomerular microangiopathic lesions detected as endothelial swelling, a double contour of the basement membrane, and intracapillary fibrin deposits by light and electron microscopy. Immunofluorescent analysis showed that fibrinogen deposition colocalized with the endothelial cell markers. The lesions were observed in only one rat (11%) in Group II. The glomerular blood flow decreased significantly in Group I compared with Group III (P Ͻ 0.05, 218.7 Ϯ 122.0 vs 883.2 Ϯ 122.0 µm/s).Conclusion. The glomerular lesions induced by injecting LPS in pregnant rats showed endothelial cell abnormalities and secondary intracapillary coagulation. We consider that these glomerular lesions were "specified" during gestation, and they had many histopathological and physiological findings in common with human preeclamptic nephropathy.