孕期苯并(a)芘暴露对仔鼠肝细胞凋亡相关蛋白表达水平的影响

Effects of Prenatal Exposure to Benzo(a) pyrene on the Expression of Apoptosis-related Proteins in Liver Cells of Offspring

目的探讨孕期不同剂量苯并(a)芘暴露对仔鼠肝脏凋亡相关蛋白Bcl-xl和Bax表达水平的影响。方法将雌雄大鼠合笼后雌性SD大鼠见阴栓确定为受孕,以检出日为孕期第0 d。将孕鼠随机分为4组,每组8只,分为对照组(玉米油)和苯并(a)芘处理组(0.75 mg/kg、1.5 mg/kg和3 mg/kg)。从妊娠第3 d开始经灌胃苯并(a)芘直到妊娠第17 d结束,分别在孕0、4、7、14、19 d称孕鼠体重。待其自然分娩后24 h内测量仔鼠的体重、身长及尾长,然后取仔鼠肝脏,采用Western blot方法检测仔鼠肝脏中Bcl-xl和Bax蛋白的表达水平。结果随着孕期苯并(a)芘暴露水平的增加,新生仔鼠体重、身长、尾长等生长发育指标均有一定程度的下降,但未达到显著性差异(P>0.05)。Western blot结果显示,与对照组相比,中、高剂量染毒组仔鼠肝脏的Bcl-xl蛋白表达均明显下降,Bax蛋白表达均明显升高,差异均有统计学意义(P<0.05或P<0.01)。结论本研究建立了一种低水平的苯并(a)芘暴露模型,随着孕期苯并(a)芘染毒剂量的增加,新生仔鼠肝脏的凋亡相关蛋白Bcl-xl/Bax比值下降,提示细胞凋亡可能是参与孕期苯并(a)芘暴露导致新生仔鼠肝脏毒性作用的机制之一。

Objectives To investigate the expression of apoptosis-related proteins Bcl-xl and Bax in the liver of offspring after Benzo（a） pyrene （BaP） exposure of pregnant rats. Methods Pregnant SD rats were randomly divided into four groups： one vehicle control （ corn oil） and three BaP-treated groups （0.75 mg/kg, 1.5 mg/kg and 3 mg/kg） （n = 8）. BaP solutions were given by intragastric administration from the 3ra day to the 17th day of pregnancy. The body weight of pregnant rats was measured. After birth, the body length, tail length and weight of the offspring were observed, and the livers were removed by the end of the experiment. Western blot method was used to detect Bcl-xl and Bax protein levels in the liver of the offspring. Results With the increasing levels of BaP exposure during pregnancy, the growth indicators of newborn pups （such as body weight, length, tail length） were decreased, but no significant difference between the groups was observed （P 〉 O. 05）. The results from Western blot showed that, compared with the control group, the expression of Bcl-xl protein in the liver of offspring was sig- nificantly decreased in the middle and high dose groups, while the expression of Bax protein was significantly in- creased （P 〈0.05 or P 〈0. O1 ）. The ratio of Bcl-xl/Bax was also decreased with the increasing of BaP exposure. Conclusions A low-dose BaP exposure model in pregnant rats was developed. With the increase of BaP exposureduring pregnancy, the ratio of apoptosis-related protein Bcl-xl/Bax in newborn liver was decreased; it suggested that apoptosis might be one of the mechanisms in the toxic effects of BaP on the liver of offspring.