Hao Xue-Qin, Kong Tao, Zhang Shou-Yan, Zhao Zhen-Sheng
Department of Pharmacology, College of Animal Science and Technology, Henan University of Science and Technology, Luoyang 471003, China.
Exp Toxicol Pathol. 2013 May;65(4):433-9. doi: 10.1016/j.etp.2012.01.001. Epub 2012 Feb 18.
Prenatal exposure to LPS(lipopolysaccharide) results in renal damage in offspring rats, but the mechanism is unknown. The present study was to explore the role of angiotensin II and inflammation in the development of renal damage induced by prenatal exposure to LPS. The pregnant rats were randomly divided into two groups, i.e., control group, LPS group. The rats in the two groups were administered intraperitoneally with vehicle or 0.79 mg/kg LPS on 8th, 10th and 12th day during gestation. The mRNA expression of angiotensinogen, renin, AT(1)-R, AT(2)-R, TNF-α and IL-6 in embryos were assessed. Renal Ang II-positive cells, monocytes/macrophages, lymphocytes, collagen I and TUNEL-positive cells were identified by immunohistochemical staining in newborn and 7-week-old offspring rats. The number of glomeruli and creatinine clearance rate were determined in offspring at 7 weeks of age. The results showed that prenatal LPS decreased AT(2)-R mRNA expression but increased TNF-α and IL-6 mRNA expression in embryos. Prenatal LPS decreased renal angiotensin II-positive cells in newborn offspring rats, while these increased in 7-week-old offspring rats. Prenatal LPS decreased glomerular number and creatinine clearance rate but increased renal infiltrating monocytes/macrophages and lymphocytes at 7 weeks of age. Prenatal LPS also increased TUNEL-positive cells and collagen I expressions in newborn rats and 7-week-old offspring rats.
Alteration of embryonic AT(2)-R and inflammatory cytokines gene expression induced by prenatal exposure to lipopolysaccharide affects renal development.
产前暴露于脂多糖（LPS）会导致子代大鼠肾损伤，但其机制尚不清楚。本研究旨在探讨血管紧张素II和炎症在产前暴露于LPS所致肾损伤发展过程中的作用。将怀孕大鼠随机分为两组，即对照组和LPS组。在妊娠第8、10和12天，两组大鼠分别腹腔注射溶剂或0.79mg/kg LPS。评估胚胎中血管紧张素原、肾素、AT（1）-R、AT（2）-R、TNF-α和IL-6的mRNA表达。通过免疫组织化学染色鉴定新生和7周龄子代大鼠肾组织中血管紧张素II阳性细胞、单核细胞/巨噬细胞、淋巴细胞、I型胶原和TUNEL阳性细胞。测定7周龄子代大鼠的肾小球数量和肌酐清除率。结果显示，产前LPS降低胚胎中AT（2）-R mRNA表达，但增加TNF-α和IL-6 mRNA表达。产前LPS降低新生子代大鼠肾组织中血管紧张素II阳性细胞数量，而在7周龄子代大鼠中这些细胞数量增加。产前LPS降低7周龄子代大鼠的肾小球数量和肌酐清除率，但增加肾组织中浸润的单核细胞/巨噬细胞和淋巴细胞数量。产前LPS还增加新生大鼠和7周龄子代大鼠肾组织中TUNEL阳性细胞数量和I型胶原表达。
产前暴露于脂多糖诱导的胚胎AT（2）-R和炎性细胞因子基因表达改变影响肾脏发育。
