甲基斑蝥胺片对Beagle犬尿液微量蛋白和尿酶的影响  

Effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs

作　　者：罗先钦[1] 杨雪[1] 胡荣[2] 黄文涛[1] 兰波[1] 涂如霞[1] 刘剑毅[1] 

机构地区：[1]重庆市中药研究院中药药理毒理研究所,重庆400065 [2]重庆市中药研究院中药药剂研究所,重庆400065

出　　处：《中国中药杂志》2014年第22期4426-4429,共4页China Journal of Chinese Materia Medica

基　　金：重庆市科委重点项目(cstc2012pt-kyys10001;cstc2012pt-kyys10004;cstc2013jcsf0118;cstc2014yykfc10002);重庆市卫生局项目(2011-2-119)

摘　　要：目的:探讨甲基斑蝥胺片对Beagle犬肾毒性以及对其尿液微量蛋白和尿酶的影响。方法:24只Beagle犬,雌雄各半,随机分4组,每组6只,即阴性对照组(空白片)、甲基斑蝥胺片6.11,12.21,24.42 mg·kg-1剂量组,连续口服给药30 d,每天1次。药物组及对照组Beagle犬在给药后1,2,3,4周,进行新鲜尿液采集,将尿液进行尿常规检测;给药第15,30天检测血清尿素氮(BUN)、肌酐(Crea)、总蛋白(TP)和白蛋白(ALB)以及钠、钾、氯电解质;给药第15,30天检测尿液微量白蛋白(m Alb)、肾脏损伤分子-1(KIM-1)、中性粒细胞明胶酶相关脂质运载蛋白(NGAL)、N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、丛生蛋白(clusterin)、β2-微球蛋白(β2-MG)、α1-微球蛋白(α1-MG)、丙氨酸氨肽酶(AAP)和免疫球蛋白Ig G。结果:与对照组相比,各剂量组尿液中尿蛋白和白细胞增加;连续15 d口服甲基斑蝥胺,各剂量组m Alb均升高,其中高剂量组KIM-1,NGAL,clusterin,NAG和AAP含量均明显升高,中、低剂量组未见统计学差异,同时血SCr和BUN未见明显异常;连续30 d给药后,各剂量组m Alb,KIM-1,clusterin,NAG,AAP均升高,呈量效关系,其中高剂量组NGAL及β2-MG含量明显升高。以上指标的含量均随着剂量的增加及时间的延长而明显升高,与血清中BUN,SCr呈相关性,提示尿液m Alb,KIM-1,clusterin,NAG和AAP指标,能够灵敏反映微量尿蛋白和尿酶的变化。结论:甲基斑蝥胺片具有一定的肾脏毒性,尿液m Alb,KIM-1,clusterin,NAG和AAP指标可做为评价甲基斑蝥胺早期肾毒性的生物标志物。Objective： To investigate the nephrotoxic effects of methyl cantharidimide tablets on urinary protein and enzymes in Beagle dogs. Method： Beagle dogs were randomly divided into negative control group（ blank tablet）,methyl cantharidimide tablets group（ 6. 11,12. 21,24. 42 mg·kg-1）,continuously 30 days of oral administration,once a day. The drug and control group were collected and determined fresh urine in 1,2,3 and 4 weeks of the administration; Serum urea nitrogen（ BUN）,creatinine（ Crea）,total protein（ TP） and albumin（ ALB） as well as sodium,potassium,chloride electrolyte were determined on 15 and 30 days of the administration; Urine albumin（ m Alb）,kidney injury molecule-1（ KIM-1）,neutrophil gelatinase-associated lipocalin（ NGAL）,N-acetyl-β-D-glucosaminidase（ NAG）,clusterin,β2-microglobulin（ β2-MG）,α1-microglobulin（ α1-MG）,alanine aminopeptidase（ AAP） and immunoglobulins Ig G were tested on 15 and 30 days of the administration. Result： Compared with the control group,urine protein and white blood cells was significantly increased in each dose group. On 15 days of the administration,m Alb were higher in each dose group,KIM-1,NGAL,clusterin,NAG and AAP were significantly higher in high-dose group,while the middle and low dose group had no significant difference,as well as blood SCr and BUN no obvious abnormalities. On 30 days,m Alb,KIM-1,clusterin,NAG,AAP were increased in each dose group,appearing dose-effect relationship,β2-MG and NGAL levels were significantly increased in high-dose group. Contents above indicators were increased with significant dose and time relationship,and serum BUN,Scr were correlated,suggesting that urine m Alb,KIM-1,clusterin,NAG and AAP indicators that can sensitively respond the changes of proteins and enzymes in urine. Conclusion： Methyl cantharidimide tablets has a renal toxicity,urine m Alb,KIM-1,clusterin,NAG and AAP can be used as the early nephrotoxic biomarkers of methyl cantharidimide tablets.

关 键 词：甲基斑蝥胺 肾毒性 尿酶 尿蛋白 

分 类 号：R96[医药卫生—药理学]