锌对染汞孕鼠胚胎毒性的影响及其机理研究

目的:探讨妊娠期补锌对染汞孕鼠胚胎发育毒性的保护作用.方法:建立孕鼠动物模型,应用不同剂量的氯化甲基汞(0.01、0.05、2.00mg/kg·d)及5.00mg/kg·d硫酸锌于妊娠6～9天连续灌胃.蒸馏水灌胃为对照组,观察孕鼠及胚胎的汞毒性及硫酸锌的影响.应用ICP-MS法测定各组胎鼠脑组织汞含量;Western blot法检测各组胎鼠脑bcl-2蛋白表达情况;TUNEL法检测各组胎鼠脑细胞凋亡情况.结果:各组均未发现死胎、吸收胎及畸形胎;0.01、0.05mg/kg·d氯化甲基汞对孕鼠及胎鼠生长发育没有明显的抑制作用;2.00mg/kg·d氯化甲基汞可以明显抑制孕鼠体重增长及胎鼠身长、体重及尾长的增长(P＜0.05),但对孕鼠产仔数、胎窝总重及胎盘总重没有明显的影响,0.05mg/kg·d、2.00mg/kg·d 氯化甲基汞组胎鼠脑组织汞含量较对照组明显升高(P＜0.05),bcl一2蛋白表达明显下降(P＜0.05),脑细胞凋亡较对照组明显升高(P＜0.05);应用硫酸锌预处理后,氯化甲基汞对孕鼠及胚胎的毒性作用明显降低(P＜0.05),胎鼠脑组织汞含量较染汞组明显降低(P＜0.05),bcl-2蛋白表达明显升高(P＜0.05),胎鼠脑细胞凋亡明显降低(P＜0.05).结论:孕期补锌可以降低氯化甲基汞对孕鼠胚胎的毒性作用,其机制与锌通过升高bel-2蛋白的表达而抑制细胞凋亡有关.

Toxicological effects of in utero exposure of rats to methylmercury chloride and the Antagonism of Zinc

Objective: To investigate the protection of zinc to the embryotoxicity of rat caused by methylmercury chloride.Methods: Establish the gestational rats' model. The rats were perorally perfused with 0.01, 0.05, 2.00 mg/ (kg·d) methylmercury chloride and 5.00mg/kg·d zinc during the period from the 6th day to the 9th day after conception respectively. The rats in the control group were perorally perfused with Double-distilled water at the same time. Then the embryotoxicity was observed. The mercury content which was in the brain of the embryos in every group was tested with ICP-MS method. The expression of Bcl-2 protein was detected by Western blot. Apoptosis in brain were tested with TUNEL method. Results: There was no dead, absorbed or deformed fetus in every group. The growth of the gestational rat and the embryos were no changed at doses of 0.01,0.05mg/kg·d methylmercury chloride. At the dose of 2.00mg/kg·d, methylmercury chloride could inhibit not only the growth of the embryos in body weight, length and tail but the weight of the gestational rat (P＜0.05),There was no significant influence on the litter size of pregnant rat, total weight of fetal or placenta; The mercury content which was in the brain of the embryos in 0.05, 2.00 mg/ (kg·d) MeHg-exposed groups was significantly higher than that in the control group(P＜0.05), Bcl-2 protein expression was decreased obviously (P＜0.05),Apoptosis in brain was significantly higher comparing with control group (P＜0.05); Using of zinc decreased the embryotoxicity of methylmercury chloride (P ＜0.05), and the mercury content was significantly lower (P ＜0.05), Bcl-2 protein was increase expression, Apoptosis in brain was significantly lower comparing with 0.05, 2.00 mg/ (kg·d) Me Hg-exposed groups (P＜0.05). Conclusions: The using of zinc during pregnancy period of rat decrease the embryotoxicity of embryos caused by methylmercury chloride. The protection mechanism may be that Zinc can inhibit apoptosis by regulatting the expression of bel-2 protein to antagonize the toxicity of mercury.