sured.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,lipid deposit could be seen in glomeruli and interstitium.The amount of fibronectin and transforming growth factor β(TGF-β)in renal cortex both increased.After serum triglyceride were decreased by fenofibrate,there were less lipid deposition in kidneys of rats(Group FAB),the UAE decreased and renal histological changes improved.The amount of FN and TGF-β in renal cortexes were down-regulated.ConclusionThese results indicated that hypertriglyceridemia expresses nephrotoxicity to rats and may exacerbate adriamycin-induced nephropathy.Triglyceride may do more harm to kidneys of animals and human than we had understood.
Key wordstriglycerideadriamycin-induced nephropathyrenal histological changetransforming growth factor-βfibronectin
人们对肾脏病与高胆固醇血症的关系目前已有较深程度的认识,已明确高胆固醇血症可通过脂质在肾小球内的沉积,启动对肾脏的损害,表现出“肾毒性”[1],而对高甘油三酯(TG)血症与肾脏病关系如何所知甚少。晚近研究结果表明,TG可能与胆固醇一样,作为一个独立的危险因素,在肾脏病的发生、发展以及预后中起着重要的作用。为证明此点,笔者以临床和肾脏病理改变酷似人类局灶节段性肾小球硬化的阿霉素(ADR)肾病[2]作为实验动物进行了长达16周的实验观察,以明确外源性高TG血症是否造成肾脏损害以及其能否加重原有的肾小球病变,从而初步了解TG有无肾毒性。
1资料与方法
1.1动物和试剂雄性SD大鼠40只,体重160~200g,上海第二军医大学实验动物中心提供。果糖由上海增健试剂公司进口分装,非诺贝特(商品名利必非)由上海爱克发制药有限公司惠赠,血脂检测试剂盒为上海长征制剂公司产品,尿纤维连接蛋白(FN)检测试剂盒为上海太阳生物技术公司产品,RT-PCR检测试剂盒为Promega公司产品。
1.2动物分组大鼠在适应性喂养2周后,按照完全随机设计原则分为5组:(1)正常对照组(C组,n=6):大鼠接受单次尾静脉注射6ml/kg体重的生理盐水,饮自来水;(2)果糖饲喂组(F组,n=6):大鼠接受单次尾静脉注射6ml/kg体重的生理盐水,饮含10%果糖的自来水;(3) ADR肾病组(A组,n=8):大鼠接受单次尾静脉注射6mg/kg的阿霉素溶液,饮自来水;(4)ADR肾病+果糖饲喂组(FA组,n=10):大鼠接受单次尾静脉注射6mg/kg的阿霉素溶液,饮含10%果
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