非诺贝特对阿霉素诱导的肾病模型大鼠的肾脏保护作用及机制  

Renal protective effect of fenofibrate on rats with adriamycin-induced nephrotic syndrome and the underlying mechanism

作　　者：张冕[1] 于海涛 王磊[1] 宋国巍[1] 桑大华[1] 孙亮[1] 魏海峰[1] ZHANG Mian;YU Haitao;WANG Lei(Jilin Province People’s Hospital,Jilin,Changchun 130021,China)

机构地区：[1]吉林省人民医院,长春市130021

出　　处：《河北医药》2024年第14期2108-2112,共5页Hebei Medical Journal

基　　金：吉林省卫生健康科技能力提升项目(编号:2017Q006)。

摘　　要：目的 研究非诺贝特对阿霉素诱导的肾病模型大鼠血脂、肾脏功能和形态的改变以及氧化应激、炎症、凝血因子的影响,探讨非诺贝特的肾脏保护作用并分析其机制。方法 将30只雄性SD大鼠随机分为正常对照组、模型组和治疗组,分别于实验第1天、第7天尾静脉注射阿霉素4 mg/kg、2 mg/kg,制备肾病综合征大鼠模型,正常对照组尾静脉注射等量0.9%氯化钠溶液。造模第8周后,治疗组大鼠给予非诺贝特(60 mg/kg)水溶液灌胃,其余2组给予等量0.9%氯化钠溶液灌胃。观察3组大鼠的一般状态、饮食、尿量及体重等变化。收集大鼠24 h尿液,利用考马斯亮蓝法检测24 h尿蛋白定量。实验结束后留取肾组织及血液标本,HE染色观察肾组织病理改变,生化分析仪检测3组大鼠血清肌酐(CRE)、血尿素氮(BUN)、胆固醇(TC)、三酰甘油(TG)水平,试剂盒检测3组大鼠肾组织匀浆中丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)、超氧化物歧化酶(SOD)、过氧化氢酶(CAT)水平,酶联免疫吸附法检测血清C反应蛋白(CRP)和血浆纤维蛋白原(FG)水平。结果 与正常对照组比较,模型组大鼠一般状态差、体重逐渐减轻、24 h尿蛋白水平、血清CRE、BUN、TC、TG水平显著升高,肾小球及肾小管形态异常,表明肾病综合征大鼠模型制备成功;非诺贝特可显著改善肾病综合征模型大鼠的肾脏病理改变,治疗组大鼠体重较同期模型组普遍偏高,第8周时,2组间差异有统计学意义(P<0.01),24 h尿蛋白水平较同期模型组明显降低,第8周末更为显著(P<0.01),血清CRE、BUN、TC、TG水平显著降低,2组间差异均有统计学意义(P<0.05)。与模型组比较,治疗组大鼠肾组织中MDA含量显著降低,GSH-Px、SOD活性显著升高,血清CRP和血浆FG水平显著降低,差异均有统计学意义(P<0.05或<0.01)。结论 非诺贝特可能通过降低肾病综合征大鼠血脂及氧化应激、炎性因子和凝血因子的表�Objective To observe the effects of fenofibrate on blood lipid,renal function and morphology,oxidative stress,inflammation and coagulation factors in rats with adriamycin-induced nephropathy,and to explore the renal protective effect of fenofibrate and its mechanism.Methods Thirty male Sprague Dawley(SD) rats were randomly divided into normal control group,model group and treatment group.Adriamycin 4 mg/kg and 2 mg/kg were injected into the tail vein on the first day and the seventh day of the experiment,respectively,thus creating the nephrotic syndrome rat model.Rats in the normal control group were injected with the same amount of normal saline through the tail vein.After 8 weeks of modeling,rats in the treatment group were intragastrically administered with fenofibrate(60 mg/kg) aqueous solution,and those in the remaining groups were intragastrically administered with an equal volume of normal saline.The general state,diet,urine volume and body weight of rats in each group were observed.The 24-hour urine of rats was collected and the 24-hour urine protein was detected by Coomassie brilliant blue method.At the end of the experiment,renal tissue and blood samples were taken.Pathological changes of renal tissue were observed by hematoxylin and eosin(H&E) staining.Serum creatinine(CRE),blood urea nitrogen(BUN),cholesterol(TC) and triglyceride(TG) were measured by a biochemical analyzer.Malondialdehyde(MDA),glutathione peroxidase(GSH PX),superoxide dismutase(SOD) and catalase(CAT) levels in renal tissue homogenate were detected by commercial kits.Serum C-reactive protein(CRP) and plasma fibrinogen(FG) were detected by enzyme-linked immunosorbent assay(ELISA).Results Compared with those of the normal control group,rats in the model group had a poor general state,gradual weight loss,significantly increased 24-hour urine protein,CRE,BUN,TC and TG,and abnormal morphologies of glomerules and renal tubules,suggesting the successful modeling of nephrotic syndrome.Fenofibrate could significantly alleviate the renal patholo

关 键 词：肾病综合征 大鼠 非诺贝特 氧化应激 炎症 抗凝治疗 

分 类 号：R692[医药卫生—泌尿科学]