促肾上腺皮质激素释放因子对镉的淋巴细胞免疫毒性的体内外双向调节作用

Study on the in vivo and in vitro bidirectional modification of cadmium immunotoxicity of lymphocytes by corticotropin-releasing factor

目的 探讨体内外镉的免疫功能抑制过程中促肾上腺皮质激素释放因子 (CRF)的修饰调节作用。方法 用垂体前叶细胞培养法测定中枢下丘脑和外周血浆CRF水平 ,用 [3 H TdR]掺入法分别检测体内、体外染毒时鼠脾T、B淋巴细胞增殖转化功能。结果 (1)整体实验动物各镉剂量组中枢下丘脑组织CRF水平均升高 ,有丝分裂原诱导脾T、B淋巴细胞增殖转化的刺激指数均低于对照组 ,差异均有显著性 (P <0 .0 5 ) ;下丘脑CRF水平与T、B淋巴细胞增殖指数之间呈负相关关系 (r =- 0 .6 75 0、- 0 .75 6 0 ,P <0 .0 5 ) ;外周血浆CRF水平各组间差异无显著性 (P >0 .0 5 )。 (2 )体外染毒时 ,镉明显抑制大鼠脾淋巴细胞的增殖转化 ;1.0～ 10 0 .0nmol/LCRF明显增强T、B淋巴细胞增殖转化能力 ;当以 1.0nmol/LCRF与 5～ 2 0 μmol/L氯化镉联合作用时各实验组两种免疫细胞 [3 H TdR]掺入率依然高于对照组 ,差异均有显著性 (P <0 .0 5 )。结论 体内染镉时存在中枢组织CRF介导的免疫功能抑制性调节作用 ,但体外CRF却能增强免疫细胞活性并阻断镉对鼠脾淋巴细胞的直接免疫功能抑制。CRF对镉的淋巴细胞免疫毒性具有双向调节作用。

Objective To explore the corticotropin releasing factor(CRF) mediated immunomodulation role in cadmium immunosuppression both in vivo and in vitro. Methods CRF levels of hypothalamus and blood plasma were observed by anterior pituitary cells culture assay in cadmium treated animals.Murine T and B lymphocytes mitogen induced proliferation function ( 3H TdR incorporation method) were detected in cadmium treated animals and in the cells co cultured with 5～20 μmol/L CdCl 2,1.0～100.0 nmol/L CRF,and 1.0 nmol/L CRF + 5～20 μmol/L CdCl 2 respectively. Results In cadmium treated animals,the central CRF levels were significantly higher and T,B lymphocytes stimulation indexes( SI ) were significantly lower than those in controls with a dose dependent response ( P <0.05).Central CRF level had negative correlations with both T,B lymphocytes SI ( r =-0.675 0 and -0.756 0, P <0.05).Whereas in peripheral blood plasma,no significant difference of CRF levels was found among all groups ( P >0.05).Coadministration with antagonist CRF could reduce the cadmium immunotoxicity to T,B lymphocytes proliferation.Cadmium treated T,B lymphocytes stimulation indexes were significantly lower than those in controls( P <0.05) with a dose dependent response in vitro.While treated with 1.0～100.0 nmol/L CRF,T,B lymphocytes proliferation indexes were much higher than those in controls( P <0.05),interestingly,T,B lymphocytes stimulation indexes were both still much higher than that of controls,when cells were cultured with 1.0 nmol/L CRF in combination of 5～20 μmol/L CdCl 2 ( P <0.05). Conclusions Central CRF mediated immunosuppression was shown in cadmium immunotoxicitic effects on murine splenocytes in vivo,whereas in vitro CRF could significantly enhance immunocytes proliferation function and block cadmium immunotoxicity to rat splenic lymphocytes, i.e. ,CRF could bidirectionally modify cadmium immunotoxicity as it did differently in vivo from in vitro.