异搏定和氯丙嗪对镉慢性肾毒性影响的实验研究

Effects of Verapamil and Chlorpromazine onCd-induced Nephrotoxicity

目的 对慢性镉染毒 (Cd)大鼠投予异搏定 (Ver)和氯丙嗪 (CPZ) ,探讨这两种物质对镉慢性肾损伤的影响。方法 实验用 4组大鼠 ,单纯镉染毒组和Ver、CPZ预处理组均皮下注射含Cd 1 4mg/kg的氯化镉 (CdCl2 )溶液 ,每周 3次 ,连续 6周。Ver和CPZ预处理组在每次皮下注射CdCl2 前 1h ,分别向腹腔注射Ver 4mg/kg 和CPZ 5mg/kg。对照组大鼠在相同时间注射生理盐水 5ml/kg。在实验开始后第 2 ,4 ,6周时收集尿样 ,测定尿N -乙酰 - β -D -氨基葡萄糖苷酶 (NAG)活力和尿蛋白含量。最后一次注射后2 4h处死大鼠 ,采集血液 ,取肾脏 ,测定血清尿素氮 (BUN) ,血、肾皮质和尿中的Cd、Ca及血、肾皮质中丙二醛 (MDA)含量。结果 镉染毒 4周时 ,与单纯镉染毒组比较 ,Ver和CPZ预处理组的尿NAG活力和尿蛋白含量均明显降低 ;镉染毒 6周时 ,Ver和CPZ预处理组的血Cd、血清BUN、尿Ca及肾皮质MDA含量均明显降低。CPZ预处理组肾皮质Cd和血MDA含量也明显降低。结论 Ver和CPZ具有防止镉所致慢性肾损伤的作用 ,其机制可能是减轻镉对肾脏的脂质过氧化损伤。

Objective To study the effects of verapamil (Ver) and chlorpromazine(CPZ)on nephrotoxicity induced by chronic exposure to cadmium.Methods Four groups of rats were experimented.Among them three groups were subcutaneously injected with CdCl\-2 solution (Cd \{1\^4 mg/kg\}), two of which were pretreated by ip Ver\{4 mg/kg\} and CPZ \{5 mg/kg\} respectively one hour before the injection of CdCl\-2,three times a week for 6 weeks.The control group was injected with 0\^9% NaCl solution(\{5 ml/kg\}).Urinary samples were collected at the end of the 2nd,4th and 6th week.NAG activities and protein contents in urine were determined.Experimented animals were sacrificed \{24 h\} after the final injection and their blood and kidney were collected.Cd and Ca contents in blood,renal cortex and urine and MDA contents in blood and renal cortex as well as blood urea nitrogen(BUN)were measured.Results NAG activities and protein contents in urine in both Ver and CPZ groups decreased significantly as compared with those of animals given cadmium alone at the end of the 4th week.After 6 weeks,the pretreatment of Ver and CPZ caused Cd contents in blood to reduce significantly,and BUN,Ca contents in urine and MDA contents in renal cortex as well.Moreover,CPZ obviously decreased Cd in renal cortex and MDA contents in blood.Conclusions Ver and CPZ protect rats against the toxic effects of Cd on kidney,which might be the result of weakening of lipid peroxidation induced by Cd.