镉对职业接触者肾功能、氧化应激与Nrf2转录因子表达水平的影响

Effects of Cadmium on Renal Function,Oxidative Stress and the Expression Level of Nrf2 Transcription Factor in Occupational Exposures

目的探讨镉对职业接触者肾功能、氧化应激以及转录因子NF-E2相关因子2(nuclear factor E2-related factor 2,Nrf2)的影响,为职业镉中毒的防治提供理论依据。方法选取34名镉职业接触者作为研究对象,检测尿β2微球蛋白(β2-MG)、尿白蛋白(ALB)、尿N-乙酰-β-D-氨基葡萄糖苷酶(NAG)、血尿酸和尿素氮等指标评价职业接触者肾功能损伤情况,测定超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)活力、丙二醛(MDA)与8-羟基脱氧鸟苷(8-OHdG)含量反映职业接触者氧化应激水平,检测蛋白激酶样内质网激酶(PERK)和Nrf2的蛋白含量分别反映职业接触者内质网应激状态与Nrf2转录因子的表达水平。结果在测得的各尿、血镉浓度条件下,职业接触者尿β2-MG、ALB含量、NAG活力与血尿酸、尿素氮含量差异均无统计学意义(均P>0.05),但在3～5μg/L血镉水平条件下,职业接触者体内抗氧化酶SOD与GSH-Px活性显著增高(均P<0.05),而脂质过氧化产物MDA与DNA氧化修饰产物8-OHdG的含量明显降低(均P<0.05),而且在该条件下,PERK和Nrf2蛋白含量显著升高(均P<0.05)。结论在没有慢性轻度镉中毒的前提下,镉未引起职业接触者肾功能的损伤。但较小于3μg/L和大于5μg/L的血镉浓度,在3～5μg/L血镉水平条件下,镉触发了职业接触者内质网应激反应,并通过激活PERK介导的Nrf2转录因子,诱导其下游抗氧化酶活性的升高,从而抑制了氧化损伤产物的生成,最终起到抗氧化作用。

Objective To explore the effects of cadmium on renal function,oxidative stress and nuclear factor erythroid-derived2-related factor2(Nrf2)transcription factor in occupational exposures,and to provide theoretical basis for prevention and treatment of occupational cadmium poisoning.Methods In total,34occupational exposures with exposure to cadmium were selected as research object.The urinaryβ2-microglobulin(β2-MG),albumin(ALB),β-N-acetylglucosaminidase(NAG),serum uric acid and urea nitrogen were measured to evaluate the renal function impairment in the occupational exposures.The activities of superoxide dismutase(SOD),glutathione peroxidase(GSH-Px),and the content of malondialdehyde(MDA),8-hydroxy deoxyguanosine(8-OHdG)were measured to reflect the level of oxidative stress.The protein contents of PKR-like endoplasmic reticulum kinase(PERK)and Nrf2were measured to reflect the endoplasmic reticulum stress(ERS)state and the expression level of Nrf2transcription factor in occupational exposures,respectively.Results With different blood concentration of cadmium,there were no statistically significant differences in the content of urinaryβ2-MG,ALB,the activity of NAG,the content of serum uric acid or urea nitrogen(P>0.05).But when the blood cadmium concentration was3-5μg/L,the activities of antioxidant enzymes SOD and GSH-Px were significantly increased(P<0.05),while the content of lipid peroxidation products MDA and DNA oxidative modified products8-OHdG were significantly decreased in occupational exposures(P<0.05).And the levels of PERK and Nrf2protein were significantly increased under this condition(P<0.05).Conclusion If the occupational exposures don’t have chronic mild cadmium poisoning,cadmium does not cause the renal function injury.As compared with less than3μg/L and more than5μg/L of blood cadmium levels,cadmium at blood concentration of3-5μg/L triggers the ERS response and activates PERK-mediated Nrf2transcription factor to induce the increase of the downstream antioxidant enzyme activity,which inhibits the formation of oxidative damage products.It finally plays an antioxidant effect.