氯丙嗪和维拉帕米对大鼠镉肾毒性的影响

摘要

目的研究氯丙嗪(CPZ)和维拉帕米(Ver)对由镉引起的大鼠肾毒性是否有预防作用.方法32只大鼠随机分成4组,分别为对照组、单纯染镉组、CPZ和Ver预处理组.单纯染镉组大鼠sc 7 μmol·kg-1氯化镉;CPZ和Ver预处理组分别ip CPZ 5 mg·kg-1和Ver 4 mg·kg-1,1 h后sc 7 μmol·kg-1氯化镉;对照组在相应时间内给予生理盐水,注射容量均为2 mL·kg-1.最后一次注射24h后,收集24h尿样,测定尿乳酸脱氢酶(LDH)活性、尿蛋白、尿镉、肾镉和肾皮质中的Na+-K+-ATP酶,Ca2+-ATP酶和蛋白激酶C(PKC)的活性.结果单纯染镉组与对照组比较,尿镉和肾镉含量明显升高.CPZ和Ver预处理组尿镉明显低于单纯染镉组,但肾镉无明显变化.与对照组比较,单纯染镉组尿LDH活性、尿蛋白和肾皮质中的Na+-K+-ATP酶,Ca2+-ATP酶和PKC活性明显升高.CPZ和Ver预处理组大鼠尿LDH活性、尿蛋白和肾皮质中的Na+-K+-ATP酶,Ca2+-ATP酶和PKC活性明显低于单纯染镉组.结论镉能激活Na+-K+-ATP酶,Ca2+-ATP酶和PKC的活性,而且,CPZ和Ver均可不同程度地减轻肾毒性.%AIM To study whether chlorpromazine(CPZ) and verapamil (Ver) have protective effects on the nephrotoxicity of cadmium (Cd). METHODS Thirtytwo Wistar rats were divided randomly into four groups.Each agent was injected 5 times per week for 6 weeks.The rats in Cd-treated group were sc injected with CdCl2 7μmol·kg-1. The rats of CPZ- and Ver- pretreated group were ip injected with CPZ 5 mg· kg- 1, Ver 4 mg· kg- 1,respectively, 1 h later sc injected with CdCl2 7 μ mol·kg- 1. The control group was sc injected with saline 2 mL·kg-1 at corresponding time. Twenty-four hours after the last injection, the 24-h urine samples were collected. The renal cortex was also excised. Lactate dehydrogenase (LDH) activity, protein and Cd concentration in urine were determined. The activities of protein kinase C (PKC), Na + -K + -ATPase, Ca2 + -ATPase and Cd concentration of renal cortex were also measured. RESULTS Cd concentrations of renal cortex and urine in rats from Cd-treated group were significantly higher than those of control group. Cd concentrations in urine of rats from CPZ- and Ver-pretreated groups were significantly lower than those of Cd-treated group, but there was no significant change in renal cortex. As compared with control group, LDH activity, protein content in urine and the activities of PKC, Na+ -K+ -ATPase and Ca2+ -ATPase in rnthe rats of Cd-treated group increased significantly. LDH activity, protein content in urine and activities of PKC,Na+ -K+ -ATPase and Ca2+ -ATPase in rats of CPZ- and Ver-pretreated groups were significantly lower than those of Cd-treated group. CONCLUSION Cd could activate the activities of PKC, Na+-K+-ATPase and Ca2+-ATPase. Moreover, pretreatment of CPZ and Ver could reduce nephrotoxicity of Cd.