Department of Internal Medicine, School of Medicine, University of Tokyo Toshiba General Hospital, Tokyo, Japan.
Nephrology (Carlton). 2011 Mar;16(3):304-9. doi: 10.1111/j.1440-1797.2010.01387.x.
Glomerular infiltration of macrophages is a characteristic alteration of renal pathology in hyperlipidaemic renal injury. Leukotriene B4 (LTB4) is a bioactive eicosanoid and macrophage and has two key enzymes for LTB4 synthesis, 5-lipoxygenase and leukotriene A4 (LTA4) hydrolase. The purpose of this study was to evaluate the role of LTB4 in accelerated hyperlipidaemic renal injury.
To induce accelerated hyperlipidaemic renal injury, 8 week old male spontaneously hypercholesterolaemic (SHC) rats were fed with a high cholesterol diet for 6 weeks. LTA4 hydrolase activities in the kidney and urine LTB4 levels were examined. The effects of LTB4 antagonist (ONO-4057) were also evaluated.
Urinary protein and LTB4 excretion was increased by a high cholesterol diet for 6 weeks. The scores of glomerular foam cell accumulation and sclerosis, numbers of infiltrated macrophages in glomeruli and interstitial area, LTA4 hydrolase activity in renal cortex were higher in the high cholesterol diet group than the normal diet group. LTB4 antagonist treatment reduced urinary protein and LTA4 activity and attenuated renal pathological changes.
These results suggest that LTB4 directly contributes to accelerated hyperlipidaemic renal injury and the therapeutic potential of LTB4 antagonist for renal damage induced by hyperlipidaemia.
巨噬细胞肾小球浸润是高脂血症性肾损伤病理的特征性改变。白三烯 B4（LTB4）是一种生物活性类二十烷，它在巨噬细胞中有两种关键的 LTB4 合成酶，即 5-脂氧合酶和白三烯 A4（LTA4）水解酶。本研究旨在评估 LTB4 在加速性高脂血症性肾损伤中的作用。
为了诱导加速性高脂血症性肾损伤，8 周龄雄性自发性高胆固醇血症（SHC）大鼠给予高胆固醇饮食 6 周。检测肾脏和尿液中 LTB4 水平以及 LTA4 水解酶的活性。同时评估 LTB4 拮抗剂（ONO-4057）的作用。
6 周高胆固醇饮食导致尿蛋白和 LTB4 排泄增加。高胆固醇饮食组肾小球泡沫细胞积聚和硬化评分、肾小球和间质区浸润的巨噬细胞数量、肾皮质 LTA4 水解酶活性均高于正常饮食组。LTB4 拮抗剂治疗可减少尿蛋白和 LTA4 活性，并减轻肾脏病理变化。
这些结果表明，LTB4 直接参与加速性高脂血症性肾损伤，LTB4 拮抗剂对高脂血症引起的肾脏损伤具有治疗潜力。
