金属硫蛋白对阿霉素致心肌细胞氧化损伤的保护作用

Protective effects of metallothionein on oxidative damage of cardiomyocytes induced by adriamycin

目的观察金属硫蛋白(metallothionein,MT)对阿霉素(adriamycin,ADR)致心肌细胞氧化损伤的保护作用。方法将培养的心肌细胞随机分5组进行实验:①对照组;②阿霉素(1mg/L)组;③阿霉素(1mg/L)+MT1(5×10-9mol/L)组;④阿霉素(1mg/L)+MT2(10-8mol/L)组;⑤阿霉素(1mg/L)+MT3(5×10-8mol/L)组。MTT法计算心肌细胞存活率;试剂盒检测细胞培养液乳酸脱氢酶(LDH)漏出量、细胞丙二醛(MDA)和一氧化氮(NO)含量及超氧化物歧化酶(SOD)活力。结果与对照组相比,阿霉素组心肌细胞存活率下降(P<0.01),细胞LDH漏出量增加(P<0.01),细胞MDA及NO含量升高(P<0.01),细胞SOD活力降低(P<0.01)。分别应用5×10-9,10-8,5×10-8mol/LMT与阿霉素共同处理心肌细胞,细胞存活率分别较单用阿霉素增加31.8%,47.8%和51.4%(均P<0.01);细胞LDH漏出量分别较单用阿霉素降低20.5%,23.3%和34.6%(均P<0.01);细胞MDA含量分别较单用阿霉素降低16.3%(P<0.05),21.1%(P<0.01),36.5%(P<0.01);NO含量分别较单用阿霉素降低17.7%(P<0.05),19.8%(P<0.05)和30.1%(P<0.01);心肌细胞SOD活性分别较单用阿霉素增加31.2%,36.5%和39.1%(均P<0.01)。结论阿霉素导致心肌细胞氧化损伤,外源性MT具有降低这种心肌细胞氧化损伤的作用。

Objective To explore the protective effects of metallothionein（MT） on oxidative damage of cardiomyoeytes induced by adriamycin （ADR）. Methods Cultured myocardial cells were randomly divided into five groups：control group, ADR group, ADR ＋ MT1 （ 5× 10^-9 mol/L） group, ADR ＋ MT2 （ 10 - s mol/L） group and ADR ＋ MT3 （ 5 × 10^-8 mol/L） group. The survival rate of myocardial cells was calculated by MTF assay. The outleakage of lactate dehydrogenase （ LDH）, the contents of malondialdehyde （ MDA ） and nitrogen monoxidum （ NO）, and the activity of SOD were measured by respective kits. Results Compared with control group, LDH outleakage, MDA and NO contents in cultured myocardial cells increased in ADR group（P 〈0.01 ） ,and survival rate and SOD activity of myocardial cells decreased （P 〈 0.01 ）. Compared with ADR group, the survival rates of euhured myocardial cells were increased by 31.8% （P 〈 0.01 ） ,47.8% （ P 〈 0.01 ） and 51.4% （ P 〈 0. 01 ） in ADR ＋ MT1 （ （ 5 × 10^-9 mol/L） group, ADR ＋ MT2 （ 10^-8 mol/L） group and ADR ＋ MT3 （5 × 10^-8 mol/L） group, respectively; LDH outleakage was decreased by 20.5% （ P 〈 0.01 ） , 23.3% （ P 〈 0.01 ） and 34.6% （ P 〈 0.01 ） ; M DA contents of cultured myocardial cells were reduced by 16.3 % （ P 〈 0.05 ）, 21.1% （ P 〈 0.01 ） and 36.5 % （P 〈 0.01 ） ; NO contents of cultured myocardial cells were reduced by 17.7% （ P 〈 0.05 ）, 19.8% （ P 〈 0.05 ） and 30.1% （ P 〈 0.01） ;the activity of SOD was increased by 31.2% （P 〈0.01） ,36.5% （P 〈0.01） and 39.1% （P 〈0.01）. Conclusion ADR could induce oxidative damage of cultured myocardial cells. Exogenous MT could decrease the oxidative damage of myocardial cells induced by ADR.