维拉帕米对糖尿病大鼠造影剂肾损害的保护作用及其机制

Experiment on Verapamil Hydrochloride Attenuating Calcium Overload in Cells of Contrast Media Induced Nephropathy of Diabetic Rats

【目的】探讨维拉帕米对糖尿病大鼠造影剂肾损害的保护作用及其作用机理。【方法】将50只Wistar大鼠随机分为正常鼠组(N),正常鼠造影剂组(NH),糖尿病鼠组(DM),糖尿病鼠造影剂组(CM)和糖尿病鼠应用维拉帕米后造影组(T)。检测造影后各组血肌酐(Scr),内生肌酐清除率(Ccr),尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG),并检测肾组织内皮素-1(ET-1)含量。同时留取肾脏作PAS染色并作病理形态学分析。【结果】与CM组相比,T组Scr下降(P<0.05),Ccr明显上升(P<0.01),尿NAG下降(P<0.05),肾皮质ET-1含量T组较CM组下降(P<0.05)。病理形态学发现T组肾组织损害特别是肾小管变性坏死较CM组减轻。【结论】维拉帕米能减轻糖尿病造影剂肾损害,其作用与其减轻糖尿病造影剂肾损害中ET-1参与的肾缺血再灌注损伤后引起的细胞内钙超载有关。

[Objective]To investigate the renal protection of verapamil hydrochloride on contrast media induced nephropathy in diabetic rats. [Metbods]Wistar rats（male, 160～180 g body weight） were divided into five groups： normal rats（N）, normal rats injected with contrast media（NH）,diabetic rats（DM）, diabetic rats injected with contrast medium （CM）, diabetic rats fed with verapamil hydrochloride for three days then injected with contrast medium （T）. Blood creatinine（Scr）, endogenous clearance creatinine rate （Ccr） and urinary N-acetyl-β-D-glucosaminidase （NAG） were measured. At the same time, endothelin-l（ET-1） in renal cortex was measured . The renal tissue was observed by light microscopy. [Results]Compared with CM group, Scr and NAG in T group decreased obviously ,Ccr in T group was improved, ET-1 in T group declined significantly. There was more damage in renal tubular epithelial cells in CM group than in T group in pathomorphology. [Conclusion]Verapamil hydrochloride can attenuate calcium overload during isehemia/reperfusion injury correlated with the increase of ET-1 in contrast media induced nephropathy in diabetic rats.