氯丙嗪和维拉帕米对大鼠镉肾毒性的影响(英文)

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sc7μmol·kg-1氯化镉;CPZ和Ver预处理组分别ipCPZ5mg·kg-1和Ver4mg·kg-1,1h后sc7μmol·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2mL·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。

Effects of chlorpromazine and verapamil on nephrotoxicity of cadmium in rats

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 the 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.