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目的比较肌钙蛋白、肌红蛋白、肌酸激酶同工酶3种检测方法评价早期心脏毒性的敏感性差异,寻求早期心脏毒性评价方法最优组合。方法原代培养乳鼠心肌细胞,不同剂量浓度(0、10、50和250μmol/l)的受试物(异丙肾上腺素、青霉素G)分别染毒24、48和72 h。检测各浓度组心肌细胞活性及搏动情况,检测细胞培养上清液中肌钙蛋白、肌红蛋白、肌酸激酶同工酶浓度,比较各组间差异统计学意义。结果异丙肾上腺素染毒对心肌细胞造成损伤。与对照组相比,各剂量浓度组肌钙蛋白T(cTnT)含量均显著增加(P<0.05)。分别测定对照组、异丙肾上腺素50μmol/l组染毒24、48和72 h后cTnT含量变化,24 h时实验组与对照组差异无统计学意义(P<0.05),48 h时实验组比对照组含量降低(P<0.05),72 h时实验组比对照组含量增高(P<0.05)。而青霉素G染毒后各组间、各时间点cTnT含量无明显差异。与对照组相比,各剂量浓度组、各时间点肌酸激酶同工酶、肌红蛋白浓度差异均无统计学意义。结论根据实验结果,针对异丙肾上腺素(10、50和250μmol/l)诱导的心肌细胞损伤模型,肌钙蛋白T能起到较好地预测作用,而肌酸激酶同工酶、肌红蛋白未能反映心肌细胞损伤。因此,人们仍需要寻求更优的预测心肌细胞毒性的指标。
OBJECTIVE: To compare the sensitivity of three assays of troponin, myoglobin and creatine kinase isoenzymes to evaluate the early cardiotoxicity and to find the optimal combination of early cardiotoxicity evaluation methods. Methods Primary cultured neonatal rat cardiomyocytes were exposed to different concentrations (0, 10, 50 and 250 μmol / l) of isoprenaline and penicillin G for 24, 48 and 72 h, respectively. The activity and the pulsation of cardiomyocytes in each concentration group were detected. The concentrations of cardiac troponin, myoglobin and creatine kinase isoenzyme in the cell culture supernatants were determined. The differences between the two groups were statistically significant. Results Isoproterenol exposure caused injury to cardiomyocytes. Compared with the control group, the levels of troponin T (cTnT) in each dose group increased significantly (P <0.05). The levels of cTnT in control group and isoprenaline 50 μmol / l group were measured respectively 24 h, 48 h and 72 h after exposure. There was no significant difference between the experimental group and the control group at 24 h (P <0.05) (P <0.05). Compared with the control group, the content in the experimental group increased at 72 h (P <0.05). However, there was no significant difference in cTnT content between groups after penicillin G exposure. Compared with the control group, there was no significant difference in the concentrations of creatine kinase isoenzyme and myoglobin in each dose group at all time points. Conclusions According to the experimental results, troponin T can play a good predictive role for isoprenaline (10, 50 and 250 μmol / l) -induced cardiomyocyte injury model, while creatine kinase isoenzyme, myoglobin Failed to reflect cardiomyocyte injury. Therefore, people still need to seek better indicators of myocardial cytotoxicity.