摘要
目的从免疫学角度探讨砷的肾脏毒性效应及其可能机制。方法 40只雌性C57BL/6小鼠随机分为对照组和砷暴露组。采用一次性灌胃NaAsO2方式染毒,对照组给予生理盐水,染毒24h后记录小鼠体重变化,HE染色观察肾脏病理学改变,实时荧光定量PCR法检测肾脏巨噬细胞增殖和分化能力相关免疫分子,生化试剂盒检测砷暴露小鼠肾脏氧化损伤情况。结果与对照组相比,砷暴露组小鼠体重、肾脏重量及脏器系数无明显差异(P>0.05);病理学结果显示肾小管发生空泡样改变且伴有炎性细胞浸润,肾脏内Cd11的mRNA水平明显降低(P<0.05),而ED1和PCNA的mRNA水平未见明显变化(P>0.05);肾脏内TNF-ɑ、IL-12、IL-10和Ccl17的mRNA水平明显降低(P<0.05);砷暴露组小鼠全血和肾脏中谷胱甘肽(glutathione,GSH)活性明显下降(P<0.05);肾脏丙二醛(maleicdialdehyde,MDA)水平和过氧化氢酶(catalase,CAT)水平明显增加(P<0.05)。结论无机砷暴露可能通过诱导氧化应激,调控肾脏巨噬细胞增殖和分化相关分子表达,最终导致肾毒性。
Objective To investigate the renaltoxicity ofarsenicfrom the view of immunology and the possible mechanism. Methods Fortyfemale C57 BL/6 mice were randomly divided into control groupandarsenic-treated mice.The NaAsO2 was administered by intragastrically for 24 h, control mice were treated with saline. After 24 hours, all mice were weighed and killed. HE stainwas used to observe the renal pathological changes.Through real-time PCR to determine related immune factors associated with theproliferation and differentiation of renal macrophages. The oxidative stress of kidney was detected by biochemical kit. Results Compared with the control group, the body weight, kidney weight and kidney index in arsenic-treatedgrouphave no significant differences(P>0.05);HE staining showed vacuolated in tubules and inflammatory cells infiltrationinkidney,the mRNA level of Cd11 was markedly decreased by arsenic treatment(P<0.05), while we failed to found any significant changes on the mRNA levels of ED1 and PCNA in the kidney(P>0.05);Renal TNF-ɑ, IL-12, IL-10 and Ccl17 mRNA levelswas markeddecreased(P<0.05). whole blood and renal glutathione(GSH)activities were significantly down-regulated in arsenic-treated mice(P<0.05);Maleicdialdehyde(MDA) and catalase(CAT)levels in kidney of arsenictreated group were increased(P<0.05). Conclusion Inorganic arsenic exposure may induce oxidative stress, regulate immune factors associated with the proliferation and differentiation of renal macrophages, ultimately result in renal toxicity.
作者
李靖宇
柳旭萍
许何丽
窦文静
王主
段晓旭
LI Jing-yu;LIU Xu-ping;XU He-li;DOU Wen-jing;WANG Zhu;DUAN Xiao-xu(Department of Toxicology,School of Public Health,Shenyang Medical College,Shenyang 110034;Research Center on Environment and Chronic Diseases,School of Public Health,China Medical University,Shenyang 110122,China)
出处
《解剖科学进展》
2020年第6期617-621,共5页
Progress of Anatomical Sciences
基金
国家自然科学基金青年项目(81803180)
辽宁省自然科学基金指导计划(20180550113)
沈阳市中青年科技创新人才支持计划(RC190479)
沈阳医学院博士科研启动基金(20186069)
沈阳医学院大学生科研立项(20198007)。
关键词
砷
肾脏
免疫调节
氧化应激
arsenic
kidney
immune regulation
oxidative stress