硝酸铈对BALB/c小鼠免疫功能及免疫细胞病理学的影响

Effects of cerium nitrate on immune function and immunocyte pathology in BALB/c mice

目的本研究拟评价硝酸铈对小鼠免疫功能以及免疫细胞病理学的影响。方法将50只BALB/c小鼠随机分为对照组(超纯水)、0.2、2、20和200 mg/kg·bw硝酸铈剂量组,经30 d灌胃染毒后,测定小鼠NK细胞活性、脾淋巴细胞增殖能力和免疫细胞病理学。结果与对照组相比,200 mg/kg·bw硝酸铈能明显降低小鼠的体重和脾脏系数(P<0.01)。对于适应性免疫而言,在20 m/kg·bw组观察到了T细胞增殖能力的降低(P<0.05),以及肠系膜淋巴结中B淋巴细胞比例的明显降低(P<0.05);200 mg/kg·bw硝酸铈持续染毒30 d,能够明显抑制小鼠T细胞和B细胞的增殖能力(P<0.01),降低外周血、脾(P<0.05)和肠系膜淋巴结中B细胞的比例(P<0.01),降低外周血中总T细胞的比例(P<0.05);此外,200 mg/kg·bw小鼠胸腺T细胞亚型中的双阳性细胞的比例明显降低(P<0.05),同时Th细胞(P<0.01)和CTL细胞(P<0.05)的比例明显升高。在固有免疫中,在本研究剂量范围内均未能观察到NK细胞活性的改变(P>0.05)。流式结果提示200 mg/kg·bw硝酸铈能够引起小鼠外周血和脾中单核/巨噬细胞的比例以及肠系膜淋巴结中NK细胞比例的明显升高(P<0.05)。结论硝酸铈经口暴露的免疫毒性较弱,200 mg/kg·bw剂量下能引起小鼠机体免疫系统紊乱,对固有免疫和适应性免疫均有影响。初步得出硝酸铈免疫毒性的LOEAL值为200 mg/kg·bw。

Objective To clarify the character of cerium on immune system.Methods Fifty BALB/c mice were administered with CN by gavage at 0,0.2,2,20 and 200 mg/kg·bw for 30 days,respectively.NK cytotoxicity,proliferative capacity of splenic lymphocytes,and immune cell pathology of mice were determined after 30-day gavage.Results 200 mg/kg·bw CN significantly reduced the weight and thymus index of mice(P<0.01).For innate immunity,NK cytotoxicity remained unchanged following the exposure to CN(P>0.05).However,the proportions of monocytes/macrophage in peripheral blood(PB)and spleen(P>0.05)positively increased in mice treated with 200 mg/kg·bw CN.For adaptive immunity,the CN-induced inhibition of proliferative capacity of T and B lymphocytes occurred in a dose-dependent manner,and those were suppressed most significantly in 200 mg/kg·bw(P<0.01).Compared with control mice,the proportion of B lymphocytes in mesenteric lymph nodes(MLNs)of mice treated with 20 mg/kg·bw CN decreased markedly(P<0.05).For mice exposed to 200 mg/kg·bw CN,the proportions of B lymphocytes in PB,spleen(P<0.05)and MLNs(P<0.01)and T lymphocytes in PB(P<0.05)were significantly lower than those in control mice.In addition,the proportion of CD4;and CD8;(double positive,DP)T lymphocytes decreased(P<0.01),while the proportions of CD4;CD8;(P<0.01)and CD4;CD8;(P<0.05)(single positive,SP)T lymphocytes elevated at the same time in 200 mg/kg group.Conclusion The immunotoxicity of CN is relatively weak,and the LOEAL for it could be primarily speculated to be 200 mg/kg·bw.