铅镉影响肾上腺皮质细胞分泌功能的机制与途径

Effects of lead and cadmium on the secretion of cortisol in adrenocortical cells and its mechanism and possible pathway

目的 了解铅、镉对肾上腺皮质细胞分泌功能的直接毒作用及可能的介导途径。方法原代分离培养的豚鼠肾上腺皮质细胞 ,分别以 0 0 0、6 2 5、12 5 0、2 5 0 0、5 0 0 0和 10 0 0 0 μmol/L氯化镉(CdCl2 )和 0 0 0、12 5 0、2 5 0 0、5 0 0 0和 10 0 0 0 μmol/L醋酸铅 (PbAc)处理细胞 ,在不同孵育时间 (30～2 40min)分别测定培养液皮质醇水平 ,并观察环 磷酸腺苷 (cAMP)与皮质醇分泌的相关性。结果 6 2 5～ 10 0 0 0 μmol/LCdCl2 引起细胞皮质醇分泌水平降低 ,呈现明显的剂量 效应关系 ,且与时间具有协同抑制效应。 12 5 0～ 10 0 0 0 μmol/LPbAc对皮质醇分泌的毒效应呈低剂量轻度抑制、高剂量回复正常的双相反应 ,表现为皮质醇水平在低剂量降低 (12 5 0和 2 5 0 0 μmol/L) ,而高剂量略升高 (10 0 0 0μmol/L) ,且随时间延长其效应愈为明显。cAMP随CdCl2 剂量增加而降低 ,具有剂量 效应关系 ,其变化与CdCl2 抑制皮质醇分泌具有相关性 ;而PbAc对cAMP的作用则表现为低剂量轻微抑制、高剂量升高 ,且与皮质醇分泌的变化相似。结论 在促肾上腺皮质激素存在下 ,CdCl2 可直接抑制皮质醇的合成分泌 ,PbAc对细胞分泌皮质醇功能的毒效应呈低剂量轻微抑制 ,高剂量回复正常 ,甚至诱导的双?

Objective To understand toxic effects directly on the secretion of adrenocortical cells induced by lead and cadmium and its possible mediated pathway. Methods The adrenocortical cells from male guinea pigs were dispersed and primarily isolated and cultured, and then the cells were incubated with cadmium chloride and lead acetate in doses of 0, 6 25, 12 50, 25 00, 50 00, 100 00 μmol/L and 0 00, 12 50, 25 00,50 00和100 00 μmol/L, respectively, for varied periods (30, 60, 120 and 240 min) Cortisol level in the culture medium and cellular cAMP concentration were measured, respectively, with RIA to study their correlation Results Cadmium chloride at 6 25 100 00 μmol/L for 30 240 min could cause reduction of cellular secretion of cortisol, in a dose dependent manner and interacted with incubation period Lead acetate could slightly inhibit secretion of cortosol at low dose (12 50 and 25 00 μmol/L) and reverse to normal secretion at high dose (100 00 μmol/L), showing a tendency of dual phase response The incubation period prolonged more, the more effects appeared Level of cAMP declined with the increase of dose of cadmium chloride, in a dose dependent manner and with correlation to its inhibition of cortisol secretion Lead acetate could inhibit cAMP at low dose and increase it at high dose, parallel with the changes in cortisol secretion. Conclusions With existence of ACTH, cadmium chloride could directly inhibit the synthesis and secretion of cortisol Lead acetate could slightly inhibit cortisol secretion at low dose and reverse its secretion at high dose, even inducing dual response cAMP, as an important second messenger, plays a role in synthesis and secretion of cortisol. CdCl 2 and PbAc could mediate their toxic effect on steroid hormone secretion, possibly via cAMP PKA pathway