Koshiba K, Kumano K, Watanabe T, Takashima Y, Cynshi O
Department of Anesthesiology, Kitasato University School of Medicine, Kanagawa, Japan.
Nihon Jinzo Gakkai Shi. 1997 Jul;39(5):455-63.
The effect of a high fat diet (HFD) on renal function, renal mitochondrial function and intrarenal oxygen-free radial scavenging activity were examined in the ischemia-reperfusion model of the rat kidney. Whether of not a novel lipophilic antioxidant (BO653) could minimize this effect in vivo was also investigated. Thirty minutes renal ischemia was introduced by vascular clamp in rats with or without HFD (cholesterol 1.25%). Some of the HFD rats received BO653 by gastric gavage. Creatinine clearance (Ccr) was measured 24 hours following the injury. Mitochondrial oxygen consumption and thiobarbituric acid reactive substance (TBARS), superoxide dismutase (SOD), glutathione peroxidase (GPX) and alpha-tocopherol were measured in the kidney before, 30 min ischemia and 30 min after reperfusion. HFD significantly reduced Ccr after ischemia-reperfusion (45% decreased compared to normal diet), which was ameliorated by BO653. Thirty-minute ischemia deteriorated the mitochondrial function in the normal diet (ND) group, high fat diet (HFD) group and high fat diet + BO653 (HFD + BO) group. Thirty-minute reperfusion ameliorated the mitochondrial function in all those groups. The kidney content of TBARS was not increased after the ischemia-reperfusion in all these groups. In the HFD group, the kidney content of GPX was higher than in the ND group during ischemia-reperfusion, but in the HFD group, the kidney content of SOD was significantly decreased after the thirty-minute ischemia. Thirty-minute ischemia decreased the kidney content of alpha-tocopherol in the HFD group, which was recovered by the thirty-minute reperfusion. In conclusion, a high fat diet deteriorates ischemia-reperfusion injury of the rat kidney and BO653 ameliorated this effect judged by creatinine clearance and renal mitochondrial function. Reperfusion injury could not be confirmed in the present model based on the results of lipid peroxidation and oxygen-free radical scavenging enzyme activity.
在大鼠肾脏缺血再灌注模型中,研究了高脂饮食(HFD)对肾功能、肾线粒体功能和肾内氧自由基清除活性的影响。还研究了一种新型亲脂性抗氧化剂(BO653)是否能在体内将这种影响降至最低。通过血管夹对喂食或未喂食HFD(胆固醇1.25%)的大鼠造成30分钟的肾脏缺血。部分HFD大鼠通过灌胃给予BO653。损伤后24小时测量肌酐清除率(Ccr)。在缺血前、缺血30分钟和再灌注30分钟后,测量肾脏中的线粒体氧消耗、硫代巴比妥酸反应物质(TBARS)、超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GPX)和α-生育酚。HFD显著降低了缺血再灌注后的Ccr(与正常饮食相比降低了45%),而BO653改善了这种情况。30分钟的缺血使正常饮食(ND)组、高脂饮食(HFD)组和高脂饮食+BO653(HFD+BO)组的线粒体功能恶化。30分钟的再灌注改善了所有这些组的线粒体功能。所有这些组在缺血再灌注后,肾脏中TBARS的含量均未增加。在HFD组中,缺血再灌注期间肾脏中GPX的含量高于ND组,但在HFD组中,30分钟缺血后肾脏中SOD的含量显著降低。30分钟的缺血降低了HFD组肾脏中α-生育酚的含量,30分钟的再灌注使其恢复。总之,高脂饮食会使大鼠肾脏的缺血再灌注损伤恶化,而根据肌酐清除率和肾线粒体功能判断,BO653改善了这种影响。基于脂质过氧化和氧自由基清除酶活性的结果,在本模型中未证实存在再灌注损伤。