氯丙嗪和异搏定对镉致大鼠肾毒性的影响

Effect of chlorpromazine and verapamil on the cadmium-induced PKC change in renal cortex of rats

目的研究氯丙嗪(CPZ)和异搏定(Ver)对镉中毒大鼠肾损伤及肾皮质蛋白激酶C改变的影响。方法大鼠按体重随机分成4组,第1组为对照组皮下注射0.9%氯化钠,第2组为单纯染镉组皮下注射7μmol/kg的氯化镉溶液,第3、4组分别是腹腔注射氯丙嗪(5mg/kg)和异搏定(4mg/kg);1h后皮下注射7μmol/kg的氯化镉,注射容量均为2mg/kg。染毒6周后,测定尿乳酸脱氢酶(LDH)、尿蛋白、尿镉、肾镉和肾皮质中的蛋白激酶C(PKC)的活性。结果单纯染镉组与对照组比较,尿LDH、尿蛋白和尿镉含量明显升高,肾镉及肾皮质细胞膜和细胞浆中PKC活性均明显升高,差异有统计学意义(P<0.01);CPZ干预组与单纯染镉组比较,细胞膜和细胞浆中PKC活性均有不同程度的下降,差异有统计学意义,尿LDH、尿蛋白和尿镉含量明显下降(P<0.05);Ver干预组细胞膜PKC活性低于单纯染镉组,且差异有统计学意义(P<0.05),尿LDH、尿蛋白和尿镉含量有下降趋势。结论氯丙嗪和异搏定均对镉中毒大鼠肾损伤及蛋白激酶C的改变有拮抗作用。

Objective To determine whether cblorpromazine(CPZ) and verapamil(Ver) can prevent the toxic effects of cadmium on the kidney.Methods The Wistar rats were divided into four groups by weight at random.The cadmium given alone group rats were subcutaneously(sc) injected with 7?μmol/(kg·bw) CdCl_2.The CPZ and Ver pretreatment group rats were intraperitoneally (ip) injected with 5mg/(kg·bw) CPZ,4mg/(kg·bw) Ver,respectively,one hour later sc administraded with 7?μmol/(kg·bw) CdCl_2.The control group rats were sc injected with saline at corresponding time.The volume of injection was 2ml/(kg·bw).The 24 hours urine samples were collected 24 hours after the last injection.The renal cortex was also excised.Urinary lactate dehydrogenase (LDH) activity,urinary protein and cadmium content were determined.The activities of protein kinase C and cadmium content of renal cortex were also measured.Results After administrated 6-week,urinary LDH,urinary protein and the activity of protein kinase C in cell membrane and cytochylema of renal cortex in the group given cd alone were higher than those of the control group.Compared with the rats which were only given cadmium,urinary LDH,urinary protein and contents of cadmium and the activity of protein kinass C decreased significantly in the CPZ and Ver group.Conclusion CPZ and Ver to some extent can reduce the activity of protein kinase C and the adverse effect of cadmium-induced by anti-intracellular calcium overload.