药物致横纹肌溶解的动物实验研究

Animal Studies of Drug-induced Rhabdomyolysis

目的探索他汀类药物、贝特类药物联合给药在大鼠、小鼠中导致横纹肌溶解的情况,为后续进行哈夫病等病因不明的横纹肌溶解综合征研究提供参考。方法采用辛伐他汀、吉非罗齐联合给药及单独给药对Wistar大鼠(5周龄)、ICR小鼠(5周龄)连续灌胃给药14 d,测定血清肌酸激酶(CK)、肌红蛋白(MYO)、谷草转氨酶(AST)、谷丙转氨酶(ALT)的含量,对其肌肉损伤指标变化趋势进行分析。在实验结束后取后肢肌肉组织进行苏木精-伊红(HE)染色病理切片检查。结果辛伐他汀、吉非罗齐连续联合给药10 d后Wistar大鼠CK、ALT、AST升高,与给药前及对照组对比差异显著(P<0.05),肌肉组织病理检查显示肌纤维坏死。ICR小鼠给药前后,与对照组相比,各生化指标无显著性差异。结论Wistar大鼠在药物作用下可发生横纹肌溶解,提示在后续进行哈夫病等不明原因横纹肌溶解动物实验研究时,可考虑使用Wistar大鼠。

Objective To explore the drug-induced rhabdomyolysis by coadministration of statin and fibrate in mice and rats to provide a reference for rhabdomyolysis caused by other reasons such as Haff disease.Method We administered simvastatin(SMV)and gemfibrozil(GF)to Wistar rats and ICR mice once daily for 14 days.The serum levels of Creatine Kinase(CK),Myoglobin(MYO)and Alanine aminotransferase(ALT),Aspartate aminotransferase(AST)were tested before and after administration.Tissue samples from skeletal muscle were stained with hematoxylin and eosin(HE)and were observed under a microscope for routine pathological examination.Result The serum levels of CK,ALT and AST after SMV and GF administration to rats 10 days were prominently increased,and the muscle fiber necrosis suggested skeletal muscle-specific toxicity.Same drugs administered mice didn’t show the increase in serum levels of biomedical parameters.Conclusion In this study,rhabdomyolysis was induced in rats by coadministration of the clinically using statin and fibrate.Wistar rats may beuseful to identify risk factors in the animal study of rhabdomyolysis such as Haff disease.