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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。
Objective To investigate whether chlorpromazine (CPZ) and verapamil have preventive effects on renal toxicity induced by cadmium in rats. Methods Thirty-two rats were randomly divided into 4 groups: control group, cadmium-only group, CPZ and Ver pretreatment group. Cadmium chloride-cadmium chloride group was only exposed to cadmium in cadmium chloride group; cadmium chloride-cadmium chloride group (ipCPZ5mg · kg-1 and Ver4mg · kg-1, sc7μmol · kg-1) Physiological saline was given within 2 mL · kg-1. 24h after the last injection, 24 h urinary samples were collected for measurement of urinary lactate dehydrogenase (LDH) activity, urinary protein, urinary cadmium, Na + K + ATPase, Ca 2+ ATPase and protein kinase C (PKC) activity. Results Compared with the control group, cadmium alone and cadmium significantly increased in cadmium group. Urinary cadmium levels in CPZ and Ver pretreatment groups were significantly lower than those in pure Cd groups, but there was no significant change in renal cadmium. Compared with the control group, urinary LDH activity, urinary protein and renal cortex Na + K + ATPase, Ca2 + ATPase and PKC activity in cadmium group were significantly increased. Urine LDH activity, Na + K + ATPase, Ca2 + ATPase and PKC activity in urinary protein and renal cortex of rats in CPZ and Ver preconditioning groups were significantly lower than that of the simple Cd group. Conclusion Cadmium can activate Na + K + ATPase, Ca2 + ATPase and PKC. Moreover, both CPZ and Ver reduced renal toxicity to varying degrees.