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[目的]探讨双酚A(BPA)对雄性小鼠心肌射血功能的影响及潜在分子机制。[方法]以C57/BL6雄性小鼠为实验动物,持续4周,每天腹腔注射染毒BPA,实验组染毒浓度分别为1、5、10 mg/kg,对照组采用同等体积生理盐水处理。应用小鼠超声仪观察左心室形态及功能的变化,采用Western blot技术检测小鼠心室组织相关的蛋白表达变化。[结果]与对照组相比,BPA 10 mg/kg组小鼠的左心室射血分数(LVEF)[(64.79±6.17)%vs(57.53±3.03)%,P<0.05]及左心室短轴缩短分数(LVFS)[(34.46±2.62)%vs(29.01±1.74)%,P<0.05]降低,而左心室舒张末期容积(LVEDV)值增高[(32.99±5.63)μL vs(37.48±2.72)μL,P<0.05]。BPA染毒组伽马组蛋白2A变异体(γH2AX)的蛋白表达水平显著增加。A型利钠肽(ANP)的蛋白表达水平呈现先增高后下降的趋势。中、高剂量BPA组小鼠心肌组织细胞外调节蛋白激酶(ERK)及丝氨酸/苏氨酸激酶1(Akt)的磷酸化蛋白表达水平显著增加。通过对比,各处理组的Brac-1蛋白表达水平差异无统计学意义。[结论]BPA可引起小鼠心室功能异常,随着BPA染毒剂量的增加,小鼠的LVEF及LVFS降低,与BPA引起的蛋白激酶pAkt及pERK表达上调呈负相关。
[Objective] To investigate the effect and potential molecular mechanism of bisphenol A (BPA) on myocardial ejection fraction in male mice. [Method] C57 / BL6 male mice were used as experimental animals for 4 weeks. The mice were injected intraperitoneally with BPA once a day for 5 and 10 mg / kg, respectively. The control group was treated with the same volume of normal saline. The morphological and functional changes of left ventricle were observed with a mouse sonicator. The changes of the protein expression in the ventricular tissues were detected by Western blot. [Results] Compared with the control group, the left ventricular ejection fraction (LVEF) [(64.79 ± 6.17)% vs (57.53 ± 3.03)%, P <0.05] (LVFS) [(34.46 ± 2.62)% vs (29.01 ± 1.74)%, P <0.05] and increased left ventricular end diastolic volume (LVEDV) [(32.99 ± 5.63) μL vs. (37.48 ± 2.72) μL, P <0.05]. The BPA-exposed gamma-histone 2A variant (γH2AX) protein expression levels were significantly increased. The protein expression level of A-type natriuretic peptide (ANP) increased first and then decreased. The levels of phosphorylated protein of myocardial extracellular regulated protein kinase (ERK) and serine / threonine kinase 1 (Akt) in medium and high dose BPA groups were significantly increased. By comparison, the Brac-1 protein expression levels in all treatment groups showed no significant difference. [Conclusion] BPA can induce ventricular dysfunction in mice. With the increase of BPA dose, the LVEF and LVFS of mice decreased, which was negatively correlated with the increase of protein kinase pAkt and pERK induced by BPA.