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作 者:杨定位[1] 林珊[1] 杨定平[2] 韦丽[1] 商文雅[1]
机构地区:[1]天津医科大学总医院肾内科,300052 [2]武汉大学人民医院肾内科
出 处:《中华医学杂志》2012年第20期1424-1427,共4页National Medical Journal of China
基 金:本研究受天津医科大学基金
摘 要:目的探讨短期和长期高胆固醇血症对低渗造影剂所致大鼠肾损害的影响及其机制。方法雄性Wistar大鼠64只,计算机随机分别给予正常饮食(32只)和高胆固醇饮食(32只),在第2及8周末,从正常饮食和高胆固醇饮食中计算机随机各取8只大鼠尾静脉注射碘海醇(10ml/kg,设为Nc组和HC组),另8只大鼠尾静脉注射等量生理盐水(设为N组和H组)。注射造影剂后24h测定大鼠血脂、肾功能及肾血流,肾皮质及尿血栓素B2、前列腺素E2(PGE2),肾皮质一氧化氮(NO)及丙二醛浓度。结果高胆固醇饮食8周大鼠注射碘海醇后血肌酐显著高于正常组[(185±28)μmol/L比(53±3)μmol/L,P〈0.01],且伴肾小管上皮细胞坏死脱落。第2周末正常饮食和高胆固醇饮食大鼠注射碘海醇后并未出现肾功能的显著改变。第8周末H组及HC组大鼠肾皮质及24h尿血栓素B2和PGE:水平均显著高于同期正常饮食大鼠,尤以血栓素B2明显;第8周末H组及HC组大鼠肾皮质NO含量显著低于N组及NC组,而肾丙二醛水平显著高于N组及NC组。结论长期高胆固醇血症是低渗造影剂所致急性肾衰竭的危险因素,脂质过氧化所致的肾内前列腺素系统的紊乱以及NO的异常是高胆固醇血症加重造影剂肾损害的原因。Objective To explore the effects of short- and long-term dietary hypercholesterolemia on contrast media-induced nephrotoxicity in rats. Methods The male Wistar rats were fed either a normal rodent diet or a high cholesterol diet. At the end of 2 and 8 weeks, 8 rats from each group received a tail vein injection of either Iohexol injection (groups NC and HC) or vehicle (groups N and H). Blood lipid, renal function, renal hemodynamics, renal and urinary prostaglandin E2 (PGE2) and thromboxane B2 (TXB2), renal nitric oxide and malondialdehyde (MDA) were determined at Day 1 following the administration of contrast media. Results The dosing of contrast media induced obviously increased serum creatinine compared with normal rats ((185±28)μmol/L vs (53±3)μmol/L,P〈0.01) and severe renal tubular necrosis in rats with a high cholesterol diet for 8 weeks but did not in normal-diet rats or rats with a high cholesterol diet for 2 weeks. The renal and urinary levels of PGE2 and TXB2 increased significantly in rats of groups H and HC at the end of 8 weeks. The renal production of nitric oxide decreased while the concentration of MDA increased markedly in groups HC and H at the end of 8 weeks. Conclusion Long- term hypercholesterolemia appears to be a risk factor of contrast media-induced acute renal failure. And it may be associated with the disorder of intrarenal prostaglandins and the abnormality of renal nitric oxide system as induced by lipid peroxidation.
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