钙离子通道阻滞剂在预防他克莫司肾毒性中的作用

目的 观察他克莫司(FK506)肾毒性模型中钙离子代谢的变化情况,探讨钙离子通道阻滞剂地尔硫草(Dil)对FK506肾毒性的预防作用.方法 按公式将肾移植术后FK506、环孢素(CsA)和Dil的首剂治疗剂量换算成大鼠的治疗剂量.雄性SD大鼠24只随机分成对照组、CsA组(25 mg·kg-1·d-1)、FK506组(0.8 mg·kg-1·d-1)和FK506加Dil组(0.8 mg·kg-1·d-1及8 mg·kg-1·d-1),每组6只,用药4周后建立各组大鼠肾毒性模型.观察各组大鼠SCr、血电解质、肾组织的病理改变(HE染色)、电子显微镜F肾脏细胞内超微结构的改变.结果 CsA组和FK506组大鼠SCr值分别为(36.00±2.61)和(34.17±4.54)μmol/L,均高于FK506加Dil组和对照组[(28.50±2.07)和(29.17±3.43)μmol/L,P＜0.05].CsA组和FK506组大鼠血钙浓度分别为(2.00±0.04)和(2.05_4-0.04)mmol/L,均低于FK506加Dil组和对照组(P＜0.05).CsA组和FK506组均可观察到肾小管细胞轻微肿胀及空泡变性、线粒体肿胀及空泡化等病理改变.与FK506组和CsA组相比,FK506加Dil组上述各项指标的变化明显减轻或接近正常.结论 钙离子代谢紊乱可能介导了FK506引起的肾毒性,Dil可用于预防FK506的肾毒性.

Preventive effect of calcium channel blocker in tacrolimus induced nephrotoxicity in rats

Objective To study the calcium metabolism in tacrolimus(FK506)induced rats nephrotoxicity and the preventive effect of calcium channel blocker.Methods Twenty-four Spragueinduced or FK506-induced nephropathy model.Blood creatinine,blood electrolytes,renal tissue histopathology(HE stain)and the change of ultrastructural organization in renal cells by transmission electron microscope were observed.Results The blood creatinine levels of both CsA and FK506 groups [(36.00±2.61)and(34.17±4.54)μmol/L] were significantly higher than those of the FK506+Dilgroup and control group(all P＜0.05).The blood calcium levels of both CsA and FK506 groups (2.00±0.04 and 2.05±0.04 mmol/L) were significantly lower than those of the FK506+Dil group and control group(all P＜0.05).The blood creatinine and calcium levels of FK506+Dil group were not significantly different with those of control group(P＞O.05).Histopathology examination showed cloudy swelling and vacuolization of the renal tubular epithelial cells and intra-cellular mitochondria swelling and vacuolization in the CsA and FK506 groups.However,the pathological changes of the FK506+Dil group were remarkably milder in comparison with the CsA and FK506 groups.Concluum channel blocker,Dil,could prevent the FK506-induced nephrotoxicity.