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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 investigate the toxic effect of the first dose of tacrolimus (FK506) on rat kidney after renal transplantation and the preventive and therapeutic effects of diltiazem (Dil) on FK506 nephrotoxicity. Methods According to the formula, the first dose of FK506, cyclosporin A (CsA) and Dil after renal transplantation was converted into the therapeutic dose of rats. Twenty-four SD rats were randomly divided into control group, CsA group (25 mg · kg -1 · d -1) and FK506 group (0.8 mg · kg -1 · d -1) And FK506 + Dil group (0.8 mg · kg -1 · d -1 and 8 mg · kg -1 · d -1). After 4 weeks of treatment, Rat kidney toxicity model. The body weight, urine samples and renal function of rats in each group were detected, and the pathological changes of renal tissues were observed. Results Both CsA group and FK506 group showed obvious increase of serum creatinine, decreased creatinine clearance, tubular cell cyst and vacuolar degeneration. FK506 + Dil group changes in the above indicators significantly reduced or nearly normal. Conclusion The first dose of FK506 after kidney transplantation is as toxic as CsA and has a toxic effect on rat kidneys. Tian heart can prevent and treat FK506 nephrotoxicity.