孕期硝酸镧暴露对子代大鼠免疫的影响

Immune response of lanthanum nitrate exposure on rat offspring

目的通过检测孕期染毒大鼠的干扰素、白细胞介素,脾T淋巴细胞、脾B淋巴细胞增殖能力,自然杀伤(NK)细胞功能等指标,探讨大鼠孕期染毒硝酸镧对子代大鼠免疫的影响。方法选取SPF级成年SD大鼠按雌雄2∶1的比例交配,每日观察阴栓确定受孕情况,获得40只孕鼠,随机分为对照组、低剂量组、中剂量组、高剂量组,每组10只,于妊娠的第7天至第16天灌胃硝酸镧溶液,剂量分别为0、2、20、60 mg/kg BW。子代大鼠出生后第4天(PND4)进行窝标准化,使得每窝子代大鼠数目均为4只,雌雄各半。断乳后子代大鼠分笼喂养,每窝选取雌雄各一只作为A队列,另每窝选取雌雄各一只作为B队列。其中A队列80只子代大鼠出生后第52天(PND52)进行免疫毒性评价,观察指标为主要脏器脏体比,外周血淋巴细胞分型以及血清γ-干扰素(γ-IFN)、白细胞介素-2(IL-2)、IL-4、IL-1α、IL-10、肿瘤坏死因子(TNF)含量的检测;B队列80只子代大鼠于出生后第55天(PND55)取脾进行T细胞依赖抗体反应试验以及检测脾T淋巴细胞和脾B淋巴细胞增殖能力。试验期间每周称取子代大鼠体质量。结果子代大鼠体质量低、中、高剂量组与对照组比较差异无统计学意义(P>0.05)。肝、肾、肺、脑、脾、胸腺相对重量与对照组比较差异无统计学意义(P>0.05)。高剂量组雄性子代大鼠脾T淋巴细胞增殖能力高于对照组,差异有统计学意义(P<0.05),且存在剂量-反应关系;试验组雌性子代大鼠全血NK细胞数量均较对照组升高,差异有统计学意义(P<0.05),且存在明显的剂量-反应关系。从试验结果得出基准剂量下限为0.21 mg/kg BW。结论本试验条件下母鼠孕期染毒硝酸镧对子代大鼠的NK细胞、脾T淋巴细胞产生轻微刺激作用,但未发现硝酸镧对子代大鼠产生免疫毒性作用。

Objective To investigate the effect of lanthanum nitrate on immune development of offspring rats,which exposed to pregnant rats,by measuring the level of interferon,interleukin,and the proliferation of spleen T lymphocyte,spleen B lymphocyte and natural killer（ NK） cells. Methods Pregnant SD rats were randomly divided into control group,low dose group,middle dose group and high dose group,with 10 rats in each group. The rats were treated with lanthanum nitrate at of 0,2,20,and 60 mg/kg BW respectively,from gestation day 7 to gestation day 16. On postnatal day 4（ PND4）,the number of rats was reduced to 4（ 2 male and 2 female per litter）,about 160 rats in the four groups. One male and one female from each litter were chosen as A queue,and the other one male and one female were B queue. On postnatal day 52（ PND52）,rats of the A queue were observed including body weight,peripheral blood lymphocyte typing and serum γ-interferon（ γ-IFN）,interleukin-2（ IL-2）,IL-4,IL-1α,IL-10,and tumor necrosis factor（ TNF） content. The rats of B queue were detected T-dependent antigen response and lymphocytes proliferation on postnatal day 55（ PND55）. Offspring rats were weighed every week during the experiment. Results There was no significant difference between the experimentalgroups and the control group（ P 0. 05）,including the relative weight of liver,kidney,lung,brain,spleen and thymus.Spleen T lymphocyte proliferation in male rats of the high dose group was higher than the control group（ P 0. 05）,with a doseresponse relationship. The number of blood NK cells in female rats of the experimental groups were more than the control group（ P 0. 05） with,a dose-response relationship. The results show that benchmark dose lower bound was 0. 21 mg/kg BW.Conclusion Exposure to lanthanum nitrate during pregnant period had a slight stimulation on NK cell and spleen T lymphocytes,however,there was no significant toxicity on the immune system development of rats offspring.