血清钴离子浓度升高对小鼠肝、肾、心脏功能与形态的影响

Effects of rising concentration of serum cobalt ions on the liver, kidney and heart in mice

目的探讨血清钴离子浓度升高对小鼠肝、肾、心脏功能与形态的影响。方法将断乳1周的40只雄性ICR小鼠（美国癌症研究所Institute of Cancer Researcch分送各国饲养实验，各国称为ICR小鼠）随机分成4组，即低剂量组、中剂量组、高剂量组和空白对照组，每组10只。实验组小鼠每天腹腔内分别注射剂量为0．82mg／kg、1．64mg／kg和3．28mg／kg氯化钴溶液（CoCl2）；空白对照组腹腔注射灭菌双蒸水。分别于注射后第4天、1、2、3周从每组小鼠眼球采血测定血清中钴离子含量，第1、2、3周测定血液生化指标[谷草转氨酶（AST）、谷丙转氨酶（ALT）、血尿素氮（BUN）、肌酐（Cr）、肌酸激酶（CK）]并作各组间的比较。第3周采用摘眼球放血方式将小鼠全部处死取心、肝、肾做病理切片及电镜观察。结果注射氯化钴溶液后第4天、1、2、3周分别测量血清中钴离子含量，结果显示随着注射剂量的增加，小鼠血清中钴离子含量相应增加，实验组之间比较差异有统计学意义。术后第1、2、3周分别测量血液生化指标，结果显示低、中剂量组AST、ALT、BUN、Cr、CK活性正常，高剂量组AST、ATJT、CK与空白对照组比较，随时间的延长氯化钴对肝、心的毒性影响有加重趋势。病理切片及电镜观察显示：各实验组的心、肝出现坏死、凋亡等病理性改变，但肾脏无毒性变化。结论高剂量的血清钴离子浓度具有肝毒性与心脏毒性，但肾毒性不显著；低、中剂量对肝、心、肾功能与形态无明显影响。

Objective To investigate the effects of serum cobalt ion concentration on the liver, kidney and heart in mice. Methods Forty 4-week-old male ICR mice were randomly divided into four groups （n=10 in each group） as follows： Group 1 （HD）, high-close cobalt chloride group （3.28 mg·kg^-1·d^-1）; Group 2 （MD）, medium-dose cobalt chloride group （1.64 mg·kg^-1·d^-1）; Group 3 （LD）, low-close group cobalt chloride group （0.82 mg·kg^-1·d^-1）; and Group 4 （NC）, normal control group （vehicle）. Cobalt chloride and normal saline were given by intraperitoneal injection once per clay for 3 weeks. The body weights of the mice were recorded every 3 days to ensure the correct doses of cobalt chloride. Blood samples for testing were taken at day 4, week 1, week 2 and week 3. Serum cobalt ion concentrations were measured in all samples whereas other serum biochemical variables, including aspartate aminotransferase （AST）, alanine transaminase（ALT）, blood urea nitrogen （BUN）, creatinine （Cr）, and creatine kinase （CK） were evaluated at week 1, 2 and 3. After killing the mice at week 3, the heart, liver and kidney were collected for pathological evaluation. Results Serum cobalt ion concentration was different between the groups. High-dose cobalt chloride significantly increased AST, ALT and CK concentrations, the concentrations increasing in parallel with treatment duration. Pathological evaluation showed that high-dose cobalt chloride had toxic effects on the heart and liver; however no significant effect was apparent in the kidney. Conclusion High-dose cobalt ion concentration in serum has toxic effects on the heart and liver, but no significant effect on the kidney in mice.