卡格列净联用阿米洛利和苯扎米尔对阿霉素诱导的肾病综合征模型大鼠的影响  

Effects of Canagliflozin Combined with Amiloride and Benzamil in Rats with Doxorubicin-induced Nephrotic Syndrome

作　　者：环薇 李潇 洪文娟 罗晓菲 HUAN Wei;LI Xiao;HONG Wenjuan(Clinical Medical College of Dali University,Yunnan 671003,China;不详)

机构地区：[1]大理大学临床医学院,671003 [2]大理大学第一附属医院肾脏内科,671013

出　　处：《医学研究杂志》2024年第9期91-97,共7页Journal of Medical Research

基　　金：云南省教育厅科学研究基金资助项目(2023Y0973);云南省大理市科技计划项目(2022KBG059);大理大学第一附属医院杰出中青年人才项目(DFYJC-202108)。

摘　　要：目的探讨卡格列净分别联用阿米洛利和苯扎米尔对阿霉素诱导的肾病综合征(nephrotic syndrome,NS)模型大鼠的影响。方法选取49只雄性SD大鼠49只,将其随机分为7组,即正常对照组(NG组)、模型组(MG组)、卡格列净组(KG组)、苯扎米尔组(BH组)、阿米洛利组(AL组)、卡格列净+苯扎米尔组(KB组)、卡格列净+阿米洛利组(KA组),每组各7只。经尾静脉注射建立NS模型。治疗前1天检测各组大鼠的24h尿蛋白定量(24h-UTP),验证模型制备成功。各组每日定时按大鼠体质量予以灌胃,NG组和MG组给予等量0.9%氯化钠溶液,疗程为6周。治疗6周后,分别检测各组大鼠尿液中24h-UTP、尿钠、尿钾、尿氯以及血清白蛋白(albumin,ALB)、甘油三酯(triglyceride,TG)、总胆固醇(total cholesterol,TC)、低密度脂蛋白(low density lipoprotein,LDL)、尿素氮(Urea)、肌酐(Crea)、胱抑素C(CysC)、血钠、血钾、血氯的表达;采用酶联免疫吸附试验(enzyme-linked immunosorbent assay,ELISA)法检测血清转化生长因子-β1(transforming growth factor-β1,TGF-β1)和可溶性血栓调节蛋白(soluble thrombomodulin,sTM)的表达;采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RT-qPCR)法检测TGF-β1基因的表达。取肾组织进行苏木精-伊红(hematoxylin-eosin,HE)染色及Masson染色观察病理学变化。结果造模成功后,MG组的24h-UTP、TG、TC、LDL水平均升高,ALB水平降低(P<0.05)。药物干预6周后,与MG组比较,各用药组的24h-UTP、TC、TG、LDL水平均降低(P<0.05),ALB水平升高(P<0.05);仅KG组的TGF-β1水平下降(P<0.05);KA组的CysC、尿钠、TGF-β1、sTM水平均升高(P<0.05)。HE染色和Masson染色结果显示,MG组大鼠肾组织出现典型的局灶节段性肾小球硬化病理特征,各用药组均出现不同程度的改善。结论单用卡格列净、苯扎米尔、阿米洛利以及卡格列净分别联用苯扎米尔和阿米洛利均可改善阿霉素Objective To investigate the effects of canagliflozin combined with amiloride and benzamir on doxorubicin-induced nephrotic syndrome(NS)model rats.Methods A total of 49male SD rats were randomly divided into 7groups:normal control group(NG group),model group(MG group),canagliflozin group(KG group),benzamil group(BH group),amiloride group(AL group),canagliflozin+benzamil group(KB group)and canagliflozin+amiloride group(KA group),with 7 rats in each group.The NS model was established by injection of doxorubicin in the tail vein.The 24h-UTP of each group was detected one day before treatment to verify the successful preparation of the model.Each group was given intragastric administration according to the body weight of rats regularly every day,NG group and MG group were given equal amount of normal saline,the course of treatment was 6 weeks.After 6 weeks of treatment,the 24h-UTP,UNa,UK,UCl levels in urine and the albumin(ALB),triglyceride(TG),total cholesterol(TC),low density lipoprotein(LDL),Urea,Crea,CysC,SNa,SK,SCl levels in serum were measured,respectively.The expression of serum transforming growth factor-β1(TGF-β1)and soluble thrombomodulin(sTM)were detected by enzyme-linked immunosorbent assay(ELISA).The expression of TGF-β1gene was detected by real-time fluorescence quantitative polymerase chain reaction(RT-qPCR).The renal pathology of rats in each group were tested by the hematoxylin-eosin(HE)staining and Masson staining.Results After successful modeling,the levels of 24h-UTP,TG,TC,LDL in the MG group were increased,while the levels of ALB was decreased(P<0.05).After 6 weeks of drug intervention,compared with MG group,the levels of 24h-UTP,TC,TG,LDL were decreased,and the level of ALB was increased in all drug groups(P<0.05),and the level of TGF-β1 was decreased in the KG group(P<0.05),and the levels of CysC,UNa,TGF-β1,sTM was increased in the KA group(P<0.05).The results of HE staining and Masson staining showed that typical characteristics of focal segmental glomerulosclerosis appeared in the renal

关 键 词：肾病综合征 局灶节段性肾小球硬化 卡格列净 阿米洛利 苯扎米尔 

分 类 号：R692.6[医药卫生—泌尿科学]