镉免疫毒性的β-肾上腺素能受体机制研究

Study on β-adrenoceptors mechanism of cadmium immunotoxicity

目的 探讨 β 肾上腺素能受体 (β受体 )途径在镉 (Cd)免疫毒性机制中的地位和作用。方法 运用 β受体阻断剂心得安 (Pro)建立肾上腺素能受体阻断的动物模型 ,观察镉单独及用心得安预处理阻断 β肾上腺素能受体后其对脾淋巴细胞 β受体密度、cAMP含量、DNA损伤程度、T淋巴细胞增殖功能及T淋巴细胞亚群的影响。结果 当单独染镉时 ,脾淋巴细胞 β受体密度在中及高剂量染镉组高于对照组 ;脾淋巴细胞cAMP含量随镉浓度的增加而增高 ,有一定的剂量 反应关系 ,并且高剂量染镉组与对照组相比较有显著性升高 ;各染镉组的T淋巴细胞增殖功能与对照比较有降低 ;DNA损伤与对照组差异有显著性。用心得安阻断 β 受体后染镉 ,可见到心得安对照组 ,心得安 +低镉组及心得安 +中镉组 β受体密度比空白对照组显著升高 ,而在低、中、高镉剂量组 β受体密度与心得安对照组相比差异没有显著性意义 ;cAMP含量、脾淋巴细胞增殖转化及T淋巴细胞亚群变化各组间差异亦没有显著性 (P >0 0 5 ) ;SCGE结果显示 ,DNA损伤程度仅在高剂量染镉组高于对照组。结论 镉的免疫毒性机制中 β

Objective To study if the beta adrenoceptors mechanism plays important role in the immunotoxicity of cadmium Methods The beta adrenoceptor density, cellular cyclic adenosine 3′,5′monophosphate(cAMP) levels, and DNA damage of rat spleen lymphocytes were studied Beta antagonist propranolol was used to block the beta adrenoceptor Results In the single Cd administration group: beta adrenoceptor density of spleen lymphocytes in the middle and high Cd concentration groups was higher than that in the non Cd treated control group ( P <0 05), the levels of cAMP increased with the increase of Cd doses, and the result of the high Cd group was higher than that of the control group ( P <0 05) The proliferation function of T lymphocytes was lower in each Cd group than that in the control group ( P <0 05) Single cell gel electrophoresis (SCGE) detected that DNA damage of spleen lymphocytes in each Cd group were more severe than the control ( P < 0 05) Pretreated with Pro group: After blocked with propranolol, beta adrenoceptor density increased in the Pro control group and the density in all Cd treated groups was higher than the control group ( P <0 05), but all Cd treated groups showed no statistical significance than the Pro control group ( P >0 05) The cAMP levels, MTT and the subsets of T lymphocytes showed no statistical significance among all the groups ( P >0 05) The results of SCGE showed that DNA damage was most severe only in the high Cd group than other groups ( P <0 05). Conclusion The results suggest that the nerve internal secretion system plays an important role in the immunotoxicity of cadmium, and the beta adrenoceptor mechanism is important in the immunotoxic mechanism of cadmium