维拉帕米对心肌细胞的保护与毒性作用

The protection and cytotoxity of verapamil on heart cells

目的研究维拉帕米(verapamil,Ver)对心肌细胞的保护作用与毒性。方法体外培养心肌细胞,测定培养液中乳酸脱氢酶(LDH)、肌酸磷酸激酶(CK)的活性;观察不同浓度维拉帕米对心肌细胞的毒性作用及对缺氧再复氧模拟"缺血再灌注"细胞的保护作用。结果连续培养96 h的结果与正常对照组相比,Ver 10.0 mg/L以上各浓度组存活细胞代谢比色值A540减少、LDH活性增高具有明显的意义;比色值A540与细胞释放的LDH、CK活性呈高度相关(r=-0.986、-0.989,P<0.01);维拉帕米可使缺血再灌注损伤的心肌细胞A540显著升高、CK显著降低。结论维拉帕米在缺氧再复氧时有明显的细胞保护作用,但是高浓度特别是超过10 mg/L时的直接细胞毒性作用值得关注。

Objective To study the protection and cytotoxity of verapamile on heart cells. Methods Heart cells were cuhured. The activity of lactate dehydrogenase and creatine phosphokinase in culture medium was detected. The toxicity of verapamil to heart cells in different concerntra/ion and protective role of verapamil to heart cells during hypoxia-reoxygennation were observed by MTT assay and testing of CK and LDH activity. Results By continuously incubation for 96 h, the value of A540 decreased and LDH activity increased in cultured heart cells with the concentration of verapamil at 10.0 mg/L or higher compared with control cells. A540 response curves were highly correlated with CK activity （ r = -0. 986, P 〈0.01 ） and LDH activity （ r = -0. 989, P 〈0.01 ）. The value of A540 significantly increase and CK activity obviously reduce in heart cells simulative ischemia and reperfusion after treatment with verapamil. Conclusion Verapamil protects heart cells in simulative ischemia and reperfusion, but the cytotoxicity is worth paying close attention when verapamil concentration is over 10 mg/L.