Study On The Heart Toxicity And The Mechanisms By BPA Exposure In Mice

Objective：To observe the toxic effects of BPA to the heart of mice, to explore the possibletoxicity mechanism of BPAfor the cardiac injury in mice by infecting the healthy KM micewith Bisphenol-A.Methods:1．The experimental group and contamination50healthy KM mice with half malesand half females, randomly divided into5groups according to the difference of weight,10mice per group, respectively giving0mg/kg,2.4mg/kg,24mg/kg and240mg/kg and480mg/kg of BPA by gastric perfusion, volume of0.01ml/g, once per day for28consecutivedays, weighing the mice twice a week during intragastric administration, to observegeneral changes of mice.2． Sampling and organ coefficient analyzing Kill the mice with cervical vertebradislocation method,cut open the chest, completely separate the heart, weigh and calculatethe organ coefficient.3． Detection method Take part of tissue fixed slices hematoxylin-eosin （HE）staining, observe and film under the microscope. After the tissue homogenate the enzymecontent Ca²⁺-ATPase is determinated by adopting spectrofluorometry. IL-6、IL-10、TNF-а、MMP-2protein expression are measured by immunohistochemistry method. QRT-PCR isused to detect the relative gene expression of cytokine.Results:1. Compared with control group, the degree of activity was decreases in exposuregroup mice and the animal wool does not light. Animal body weight increase the low dosegroup is higher than the high dose group, Difference was statistically significant（P <0.05）.2. The Exposed group compared with control group with difference of heartviscera coefficient there was no statistically significant difference （P>0.05）.3. Different degree pathologic changes in heart tissue can be seen in exposure group mice by histologic examination; and the degree of pathological change becomesmore and more significant as dose increases. It is mainly noted as myocardial fibrosisarrange loosely, broadening gap, interstitial edema, a large number of inflammatorycells infiltration, or even myocardial necrosis.4. The Ca²⁺-ATPenzyme activity is reduced in the exposure group compared withcontrol group, the difference has statistical significance （P <0.05）. There is nostatistical significance in the difference between male and female groups （P>0.05）5. The cytokine interleukin-6（IL-6）, tumor necrosis factor alpha （TNF alpha）,interleukin10（IL-10） expression is reduced In each exposure group, the difference hasstatistical significance （P <0.05）. And it showed a dose-response relationship to somedegree. matrix metalloproteinase-2（MMP-2） protein expression has no changed,The difference between each exposure mice and the control group has no statisticallysignificant difference （P>0.05）.6.The gene expression of IL-6, TNF alpha increased in each exposure group,IL-10gene expression decreased （P <0.05） in each exposure group. While geneexpression of MMP–2has no significant changed (（P>0.05）Conclusion:1. BPA can affect the animal growth and development, low dose of BPA canpromote animals’ weight growth, high dose of BPA can slower it.2. BPA can decrease Ca²⁺-ATP enzyme activity of myocardial tissue.3. BPA can increase the levels of IL-6a,TNF-αand decrease the levels of IL-10.4. The mechanism of heart toxicity may have something to do with the decreaseof Ca²⁺-ATP enzyme activity in myocardial tissue and cause of myocardialinflammation.