ABSTRACT
Objective:To explore the role of prostacyclin (PGI 2) in the development of kidney and vascular system in mice. Methods:The prostacyclin synthase ( PGIS) knockout model was established in C57BL/6J mice. The effects of PGIS knockout on the survival rate of mice were observed by genotyping analysis. The effects of PGIS knockout on the development of kidney and vascular system in mice were observed by hematoxylin and eosin staining and periodic acid-Schiff staining. The morphological changes of kidneys in PGIS knockout mice were observed. Blood urea nitrogen was tested to evaluate the function of kidney in mice. Real-time quantitative PCR was used to analyze the effect of PGIS knockout on the mRNA expression of prostaglandin synthetase PGES and TXAS. The expression of PGIS in vascular system was observed by immunofluorescence staining. The blood pressure and heart rate of mice were measured by the tail-cuff method. Results:Most of the systemic complete PGIS knockout ( PGIS-/-) fetal mice sacrificed. The kidneys of PGIS-/- fetal mice developed abnormally, which showed sparse interstitial, abnormal tissue differentiation, lengthened renal vesicle, and significant decrease in the number of "S" -shape bodies ( P<0.01). The kidneys of PGIS-/- mice showed tissue atrophy, surface irregularities and cyst formation. Blood urea nitrogen level in the PGIS-/- mice was significantly higher than that in the wild type ( PGIS+/+) mice [(36.89±5.39) mmol/L vs (5.07±0.69) mmol/L, n=3, P<0.01]. There was no significant difference in the mRNA expression of PGES and TXAS between PGIS+/+ mice and PGIS-/-mice. PGIS was widely expressed in renal vascular endothelial cells and smooth muscle cells of PGIS+/+ mice. Vascular system developed abnormally, which showed loss of smooth muscle layer, width of subendothelial loose layer, thinning of the pipe wall, and discontinuity of the inner elastic plate in PGIS+/- mice. There was no significant difference in the blood pressure and heart rate between PGIS systemic half-knockout ( PGIS+/-) mice and PGIS-/- mice. Conclusion:PGIS plays an important role in the development of kidney and vascular system in mice.