慢性锰暴露对大鼠肾脏氧化损伤和Nrf2信号通路的影响  

Influence of chronic manganese exposure on renal oxidative injury and Nrf2 signaling pathway in rats

作　　者：田应宽 王霞 周远忠 申旭波 TIAN Ying-kuan;WANG Xia;ZHOU Yuan-zhong;SHEN Xu-bo(School of Public Health,Zunyi Medical University,Zunyi 563000,China)

机构地区：[1]遵义医科大学公共卫生学院,遵义563000

出　　处：《环境卫生学杂志》2022年第3期170-176,共7页JOURNAL OF ENVIRONMENTAL HYGIENE

基　　金：国家自然科学基金(81660552)。

摘　　要：目的探讨慢性锰(Mn)暴露对SD大鼠肾脏氧化损伤和核转录相关因子2(Nrf2)信号通路的影响。方法将48只SPF级健康雄性SD大鼠随机分为高剂量组(50 mg/kg)、低剂量组(10 mg/kg)和对照组(灭菌蒸馏水),每组16只,灌胃染毒12个月。观察肾脏组织病理学变化,检测肾脏中谷胱甘肽过氧化物酶(GSH-Px)活性、丙二醛(MDA)含量和大鼠血清肌酐(Cre)、尿素氮(BUN)含量,检测核转录相关因子2(Nrf2)、血红素氧化酶-1(HO-1)、醌氧化还原酶1(NQO1)蛋白表达水平。结果高剂量组大鼠肾脏脏器系数高于低剂量组和对照组(P<0.05);高剂量组肾小球毛细血管扩张,肾小球、肾小管、肾小体内红细胞均增多。与低剂量组和对照组相比,高剂量大鼠血清中Cre、BUN和肾脏MDA水平明显升高,肾脏GSH-Px活性降低(P<0.05)。与对照组相比,低剂量和高剂量组的Nrf2、HO-1、NQO1的蛋白表达均降低(P<0.05)。结论慢性50 mg/kg Mn染毒暴露可导致肾实质通透性增加,肾脏水肿,肾功异常,其原因可能与Mn所导致的氧化损伤有关;Nrf2信号通路的抑制可能是慢性Mn暴露导致SD大鼠肾脏氧化损伤机制之一。Objective To investigate the influence of chronic manganese(Mn)exposure on renal oxidative injury and the nuclear factor erythroid 2-related factor 2(Nrf2)signaling pathway in Sprague-Dawley(SD)rats.Methods A total of 48 healthy male specific pathogen-free(SPF)SD rats were randomly divided into high-dose group(50 mg/kg),low-dose group(10 mg/kg)and control group(sterilized distilled water),with 16 rats in each group,and the rats were sacrificed after Mn exposure(intragastric administration)for 12 months.Renal histopathological changes were observed,and the activity of glutathione peroxidase(GSH-Px)and the content of malondialdehyde(MDA)in the kidney and the serum levels of creatinine(Cre)and blood urea nitrogen(BUN)were measured,as well as the protein expression levels of Nrf2,heme oxygenase-1(HO-1),and NAD(P)H:quinone oxidoreductase 1(NQO1).Results The high-dose group had a significantly higher kidney organ coefficient than the low-dose group and the control group(P<0.05).The high-dose group had dilated glomerular capillaries and a significant increase in the number of red blood cells in glomeruli,renal tubules,and renal corpuscles.Compared with the low-dose group and the control group,the high-dose group had significant increases in the serum levels of Cre,BUN and MDA,and a significant reduction in the activity of GSH-Px(P<0.05).Compared with the control group,the low-and high-dose groups had significant reductions in the protein expression levels of Nrf2,HO-1 and NQO1(P<0.05).Conclusion Chronic high-dose Mn exposure can lead to increase renal parenchymal permeability,renal edema,and abnormal renal function,which may be associated with oxidative injury caused by Mn,and inhibition of the Nrf2 signaling pathway may be one of the important mechanisms of renal oxidative injury caused by chronic Mn exposure in SD rats.

关 键 词：锰(Mn) 肾 氧化损伤 谷胱甘肽过氧化酶(GSH-Px) 核转录相关因子2(Nrf2) 

分 类 号：R114[医药卫生—卫生毒理学]