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甘油三酯肾毒性及其加重大鼠阿霉素肾病的初步研究
http://www.100md.com 《中华现代内科学杂志》 2005年第6期
甘油三酯阿霉素,甘油三酯阿霉素;肾病;肾脏病理转化生长因子;β纤维连接蛋白,1资料与方法,2结果,3讨论,参考文献
     【摘要】目的探讨甘油三酯(TG)是否具有肾毒性以及外源性TG对阿霉素肾病大鼠的影响。方法雄性SD大鼠40只,分为5组,即C组:正常对照组,F组:果糖饲喂组,A组:ADR肾病组,FA组:ADR肾病+果糖饲喂组,FAB组:ADR肾病 + 果糖饲喂组 + 非诺贝特治疗组(n=10)。实验周期为16周。在实验前、实验后第2、8和16周分别抽空腹血查肾功能、白蛋白、血脂。抽血次日留24h尿测尿蛋白定量。实验结束时采血留尿后宰杀动物,留取肾组织行光镜下观察HE、油红O染色病理学改变,测定肾脏内纤维连接蛋白(FN)和转化生长因子β(TGF-β)的含量。结果饲喂果糖可造成大鼠食饵性高TG血症,但肾脏基本无病变,肾脏内少见脂质沉积;而饲喂果糖可显著升高阿霉素肾病大鼠的血TG水平,尿蛋白排泄量显著增多,肾脏病理改变加重,肾小球和肾小管内脂质沉积增加,肾皮质FN和TGF-β的含量均较食饵性高甘油三酯血症大鼠显著增加或增强;而以吉非罗齐降低大鼠血浆甘油三酯水平后大鼠尿蛋白排泄量减少以及肾脏病理减轻,肾脏内脂质沉积明显减少,肾皮质内FN和TGF-β的含量下降。结论高TG血症对SD大鼠肾脏具毒性作用,并可加重阿霉素肾病大鼠病情和肾脏病理,提示临床重视和治疗高TG血症的必要性和紧迫性。

    关键词:甘油三酯阿霉素;肾病;肾脏病理转化生长因子;β纤维连接蛋白

    Initial study on triglyceride-nephrotoxicity and exacerbation of adriamycin-induced nephropathy by hypertriglyceridemia in rats

    Fu Peng,Yuan Weijie,Yu Guoqing,et al.

    Department of Nephrology,Changhai Hospital Affiliated to Second Military Medical University,Shanghai 200433.

    【Abstract】ObjectiveTo evaluate the possibility of triglyceride nephrotoxicity in rats and the role of exogenous triglyceride on adriamycin-induced nephropathy.Methods40 male SD rats were divided into 5 groups,that was normal controls(Group C,n=6),fructose fed group(Group F,n=8),adriamycin-induced nephropathy group(Group A,n=8),fructose fed nephropathy group (Group FA,n=10),fructose fed nephropathy rats treated with drugs (Group FAB).Group F rats drunk tap water containing fructose of 10 percent.Group A rats were injected with 6 mg/kg of adriamycin solution once.Group FA rats drunk water containing fructose of 10 percent.Group FAB rats were treated with 3 microgram fenofibrate per day.The experiment lasted for 16 weeks.The measurement of serum triglyceride and cholesterol and assessment of renal function and serum albumin and urine protein excretion amount were done during fixed intervals.The histological changes in renal tissues of rats were observed under microscope.The contents of fibronectin(FN)and transforming growth factor-β(TGF-β)in renal cortexes of rats were measured.ResultsThe animal study showed that the amount of urinary albumin excretion(UAE)in fructose-induced hypertriglyceridemia rats(Group F)was very small.The renal histological changes were mild with less lipid deposit within glomeruli or tubulo-interstitium.The adriamycin-induced nephrotic rats with endogenous hypertriglyceridemia were fed with food containing 10% fructose(Group FA).The serum triglyceride level and amount of UAE in group FA rats were higher than those in group F,and the renal histological changes were exacerbated ......

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