恬尔心对大鼠FK506肾毒性的防治作用  

Prevention of diltiazem in tacrolimus-induced nephrotoxicity:experiment with rats

作　　者：陈业辉[1] 梁颜笑[2] 陈林强[3] 梁健健[4] 张静[2] 邱江[5] 黎伟龙[1] 胡建波[1] 谢克基[1] 钟惟德[1] 陈立中[5] 郑克立[5] 

机构地区：[1]广州市第一人民医院泌尿外科,510180 [2]广州市第一人民医院病理科,510180 [3]广州市第一人民医院检验科,510180 [4]广州市第一人民医院药剂科,510180 [5]中山大学附属第一医院泌尿外科

出　　处：《中华医学杂志》2007年第32期2235-2237,共3页National Medical Journal of China

基　　金：广东省自然科学基金(06301011);广东省医学科学技术研究基金(B2006123);广州市医药卫生科技基金(2005-YB-003)

摘　　要：目的探讨肾移植术后首剂治疗剂量他克莫司(FK506)对大鼠肾脏的毒性作用以及地尔硫革(恬尔心,Dil)对 FK506肾毒性的防治作用。方法按公式将肾移植术后 FK506、环孢素 A(CsA)和 Dil 的首剂治疗剂量换算成大鼠的治疗剂量。SD 大鼠24只随机分成对照组、CsA 组(25mg·kg^(-1)·d^(-1))、FK506组(0.8 mg·kg^(-1)·d^(-1))和 FK506+Dil 组(0.8 mg·kg^(-1)·d^(-1)及8 mg·kg^(-1)·d^(-1)),用药4周后建立起各组大鼠肾毒性模型。检测各组大鼠的体重、尿标本、肾功能,以及观察肾组织的病理改变。结果 CsA 组与 FK506组均出现明显的血肌酐上升、肌酐清除率下降、肾小管细胞浊肿及空泡变性。FK506+Dil 组上述各项指标的变化明显减轻或接近正常。结论肾移植术后首剂治疗剂量 FK506与 CsA 一样,对大鼠肾脏均具有毒性作用。恬尔心可以防治 FK506的肾毒性。Objective To study the nephrotoxicity induced by first oral administration of tacrolimus （FKS06） and the prevention of dihiazem （Dil）. Methods 24 Sprague-Dawley male rats were randomly divided into 4 equal groups ： control （ n = 6） , cyclosporine A （CsA） group （ receiving CsA 25 mg· kg^-1 d ^-1 so as to develop CsA-induced nephropathy model） , FK506 group （ receiving FK506 0.8 mg · kg^-1 ·d^-1, the common renal transplantation therapeutic dose, so as to develop FK506-induced nephropathy model） , FK506 ＋ Dil group （ receiving CsA 0.8 mg · kg^-1· d^-1 and Dil 8 mg· kg^-1· d^-1 ）, and control group. Four weeks later body weight was measured, blood samples were collected to examine the creatinine, urea nitrogen, and uric acid, and urine samples were collected to examine the 24 h urine protein, uric acid, and creatinine. Then the rats were killed with their kidneys taken out to undergo histopathological examination. Results The urine creatinine levels of the CsA and FKS06 groups were significantly lower than that of the control group （ both P 〈 0.05 ） , however, there was no significant difference in urine creatinine between the FK506 ＋ Dil group and control group. The blood creatinine levels of both CsA and FK506 groups were significantly higher than those of the FK506 ＋ Dil group and control group （ all P 〈 0. 05 ） , however, there was no significant difference in blood creatinine between the FK506 ＋ Dil group and control group. The urea nitrogen level of the CsA group was significantly higher than those of the other 3 groups （ all P 〈 0.05 ）. The creatinine clearance rates of the CsA and FKS06 groups were both significantly lower than that of the control group （ both P 〈0.05） , and the creatinine clearance rate of the FK506 ＋ Dil group was between those of the FK506 group and control group, however, with significant differences with both of them. Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial

关 键 词：肾脏移植 肾毒性 他克莫司 地尔硫[艹卓] 

分 类 号：R96[医药卫生—药理学]