孕期硝酸镧暴露对子代大鼠免疫的影响

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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 effects of lanthanum nitrate during pregnancy on the offspring of pregnant rats exposed to lanthanum nitrate during pregnancy by detecting interferon, interleukin, splenic T lymphocytes, splenic B lymphocyte proliferation and natural killer (NK) Impact of rat immunity. Methods SPF adult SD rats were mated in the ratio of male and female 2: 1. The pregnant mice were observed daily for confirming their pregnancy status. Forty pregnant rats were randomly divided into control group, low dose group, middle dose group, high dose group, In each group, 10 rabbits were lavaged with lanthanum nitrate solution on the 7th day to the 16th day of gestation at doses of 0, 2, 20 and 60 mg / kg BW, respectively. Offspring rats were normalized on the fourth day after birth (PND4) so ​​that the number of offspring in each litter was 4, with half male and one female. After weaning, offspring rats were fed in cage, each male and female was selected as A cohort and the other male and female cohort as B cohort. The immunotoxicity was evaluated on PND52 in 80 offspring of A-cohort. The observation indexes were the ratio of viscera of major organs, the type of peripheral blood lymphocytes and the serum levels of IFN-γ, The levels of IL-2, IL-4, IL-1α, IL-10 and tumor necrosis factor (TNF) were detected in 80 rats of group B at day 55 after birth (PND55) Spleen T cell-dependent antibody response test and detection of splenic T lymphocytes and splenic B lymphocyte proliferation. Weeks weighing the offspring rat body mass during the test. Results There was no significant difference in the body weight of the offspring rats between the middle and high dose groups and the control group (P> 0.05). The relative weights of liver, kidney, lung, brain, spleen and thymus were not significantly different from the control group (P> 0.05). The proliferation of splenic T lymphocytes in male offspring in high dose group was higher than that in control group (P <0.05), and there was dose-response relationship. The number of NK cells in female offspring in experimental group Compared with the control group, the difference was statistically significant (P <0.05), and there is a clear dose-response relationship. From the test results, the lower limit of the baseline dose was 0.21 mg / kg BW. Conclusion In the present study, lanthanum nitrate was slightly irritated to NK cells and splenic T lymphocytes of offspring in the pregnant rats, but lanthanum nitrate was not found to produce immunotoxicity in offspring rats.
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