双酚A对小鼠心脏射血功能及5种蛋白表达的影响
Effects of bisphenol A on heart ejection and five related proteins' expressions in mice
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摘要:
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。
Abstract:Objective To verify whether bisphenol A (BPA) exposure would affect heart ejection in mice, and explore the underlying mechanisms.
Methods C57/BL6 male mice were given daily subcutaneous injection of BPA at 1, 5, and 10 mg/kg (exposure groups) or normal saline (control group) for four consecutive weeks. Ultrasound device was performed to observe the changes of left ventricular morphology and function. By Western blot test, related protein expression levels in mice ventricular tissue were determined.
Results Compared with the control group, the 10 mg/kg BPA exposure group showed significantly decreased left ventricular ejection fraction (LVEF)(64.79±6.17)% vs (57.53±3.03)%, P < 0.05 and left ventricular fractional shortening (LVFS)(34.46±2.62)% vs (29.01±1.74)%, P < 0.05; however, the level of left ventricular end-diastolic volume (LVEDV) was in creased(32.99±5.63) μL vs (37.48±2.72) μL, P < 0.05. The BPA exposure significantly increased the protein expression levels of H2A histone family member X (γH2AX). Atrial natriuretic peptide (ANP) tended to increase firstly and then decrease. In addition, the elevated phosphorylation levels of extracellular regulated protein kinase (ERK) and serine/threonine-protein kinase 1 (Akt) were also detected in the 5 and 10 mg/kg BPA exposure groups. However, we failed to observe any meaningful change of Brac-1 protein expression level after BPA exposure.
Conclusion Exposure to BPA can induce cardiac abnormality. With the increasing dose of BPA, LVEF and LVFS are decreased, which are negatively associated with the up-regulated expression of pAkt and pERK.
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