缬沙坦对阿霉素所致心肌细胞损伤保护作用的初步研究

Effects of valsartan on myocardial cell damage induced by doxorubicin

目的研究缬沙坦(valsartan,VAT)对阿霉素(doxorubicin,DOX)所致心肌细胞损伤的保护作用。方法采用不同浓度(0.5μmol/L、1μmol/L、2μmol/L、4μmol/L)DOX处理H9C2心肌细胞建立DOX心肌细胞损伤模型。CCK-8法检测细胞存活率,流式细胞仪检测细胞凋亡率和细胞周期变化。结果与对照组比较,不同浓度(0.5μmol/L、1μmol/L、2μmol/L、4μmol/L)DOX作用H9C2心肌细胞12 h和24 h,细胞存活率均随药物浓度增加而降低(P<0.01)。其中1μmol/L DOX作用24 h即可明显引起H9C2心肌细胞损伤,细胞存活率为(75.5±5.6)%,细胞凋亡率为(11.94±2.07)%,与对照组比较差异有统计学意义(P<0.05);10μmol/L的VAT预处理H9C2心肌细胞24 h后可明显抑制1μmol/L DOX引起的心肌毒性作用,与单用DOX组比较,细胞存活率升高[(74.2±3.0)%vs(89.3±4.0)%,P<0.01]、细胞凋亡率下降[(13.15±6.07)%vs(11.01±3.17)%,P<0.01]、G0/G1期细胞所占比例明显减少[(69.21±2.03)%vs(50.28±1.21)%,P<0.05]。结论 VAT能抑制DOX所致的心肌细胞损伤,保护作用可能与其调控细胞凋亡有关。

Objective To investigate the effects of Valsartan（VAT） on myocardial cell damage induced by doxorubicin（DOX）. Methods A model of DOX-induced myocardial cell damage was established by exposing H9C2 myocardial cells to different concen-trations of DOX（0.5，1，2，4 μmol/L）. Cell survival rate was detected by CCK8 colorimetry. Cell apoptosis rate and cell cycle change were detected by flow cytometry. Results The cytotoxic effects of DOX on H9C2 cells were dose- and time-dependent for concentra-tions from 0.5 to 4 μmol/L during exposure times from 12 h to 24 h. Exposure to 1 μmol/L DOX for 24 h led to significant cytotoxic effects. The treated cells showed （75.5±5.6）% of the survival rate of control cells，and the rate of cell apoptosis was （11.94±2.07）% compared to（4.86±0.56）% in control cells（P＜0.05）. Pretreatment with 10 VAT μmol/L led to significantly higher survival rate ［（89.3±4.0）% vs （74.2±3.0）%，P＜0.01］，significantly lower apoptosis rate ［（11.01±3.17）% vs （13.15±6.07）%，P＜0.01］，and significantly lower ratio of cells in G0 /G1 phase ［（50.3±1.2）% vs （69.21±2.03）%，P＜0.05］. Conclusions VAT can mitigate DOX-induced damage to myocardial cells，and the protective effect may be related to the suppression of apoptosis.