目的探讨围生期暴露双酚A(bisphenol A,BPA)对成年期雌性子代大鼠血脂及激素敏感性脂肪酶(hormone—sensitive lipase,HSL)mRNA、蛋白表达的影响。方法将21只清洁级sD妊娠大鼠分为3组,分别为对照(含1%无水乙醇的水)组和低(1μg/ml)、高(10μg/m1)剂量BPA暴露组,每组7只。从妊娠第6天至哺乳期(出生后20d),母鼠采用自由饮水方式染毒;断乳后,雌性仔鼠采用自由饮水(不含BPA)方式继续喂养80d。测定雌性仔鼠体重、空腹血脂[包括血清甘油三酯(triglycerides,TG)、总胆固醇(total cholesterol,TC)、高密度脂蛋白胆固醇(high density lipoprotein cholesterol,HDL—C)和低密度脂蛋白胆固醇(low density lipoprotein cholesterol,LDL—C)1,并检测内脏脂肪组织HSLmRNA及蛋白的表达水平。结果与对照组比较,各剂量BPA染毒组子代雌鼠体重显著增高,各剂量BPA暴露组雌性仔鼠血清中HDL—C水平降低,仅高剂量BPA暴露组血清中TG水平增高,差异均有统计学意义(P〈0.01);而各剂量BPA暴露组雌性仔鼠血清中TC和LDL—C水平均无明显改变。与对照组比较,各剂量BPA暴露组雌性仔鼠脂肪组织中的HSLmRNA和蛋白表达水平均降低,差异有统计学意义(P〈0.05);且随着BPA暴露剂量的升高,雌性仔鼠脂肪组织中的HSLmRNA和蛋白表达水平均呈下降趋势。结论发育早期暴露BPA可引起成年期子代雌鼠体重增加和血脂代谢紊乱,这可能与其下调内脏脂肪组织HSL表达有关。
Objective To study the effects of bisphenol A (BPA) exposure during perinatal period on the levels of serum lipids and hormone-sensitive lipase (HSL) mRNA and protein expression in female offspring rats. Methods A total of 21 pregnant Sprague-Dawley rats were randomly divided into three groups, seven rats in each group,the control group (1% of anhydrous alcohol with water),low dose (1 μg/ml) and high dose (10 μg/ml) groups of BPA exposed through drinking water,from gestation day 6 to the end of lactation respectively. The female offspring were raised for 80 days by drinking water (without BPA) at liberty after weaning.The body weight and serum lipids including triglycerides (TG), total cholesterol (TC), high and low density lipoprotein cholesterol (HDL-C and LDL-C) in female offspring were measured. The levels of HSL mRNA and protein expressions in visceral adipose tissue were also determined. Results There were significantly higher level of body weight and lower serum HDL-C level in BPA-exposed rats compared with controls, but serum TG level was significantly higher only in high dose of BPA group, the above differences were statistically significant (P〈0.01). There were no significant differences in the levels of serum TC and LDL-C between BPA-exposed rats and controls. The levels of HSL mRNA and protein expression were significantly lower in visceral adipose tissue of BPA-exposed female offspring than controls (P〈0.05), and showed a decreased trend with increasing BPA doses. Conclusion BPA exposure during early development may induce an increased body weight and dyslipidemia, which is associated with low expression of HSL in visceral adipose tissue.