LIGHT/TNFSF14减轻顺铂诱导的小鼠急性肾损伤及机制  

LIGHT/TNFSF14 alleviates cisplatin-induced acute kidney injury in mice and its mechanism

作　　者：杨雁 钟渝 孟利 谢攀 许桂莲 彭侃夫 YANG Yan;ZHONG Yu;MENG li;XIE Pan;XU GuiHan;PENG Kanfu(Department of Kidney Diseases,Southwest Hospital,Army medical university,Chongqing 400038,China;Department of Immunology,School of Basic Medicine,Army medical university,Chongqing 400038,China)

机构地区：[1]陆军军医大学西南医院肾科,重庆400038 [2]陆军军医大学基础医学院免疫学教研室,重庆400038

出　　处：《细胞与分子免疫学杂志》2019年第10期897-902,共6页Chinese Journal of Cellular and Molecular Immunology

基　　金：国家自然科学基金(81873606,81370836)。

摘　　要：目的研究与单纯疱疹病毒糖蛋白D竞争结合疱疹病毒侵入介体的淋巴毒素类似物(LIGHT)即肿瘤坏死因子超家族蛋白14(TNFSF14)在顺铂诱导的急性肾损伤(Cis-AKI)中的作用并初步探讨其机制.方法选取雄性野生型(WT)和LIGHT敲除(LIGHT^-/-)C57BL/6小鼠,分为WT小鼠生理盐水组、WT小鼠顺铂组、UGHT^-1-小鼠生理盐水组和LIGHT^-1-小鼠顺铂组.其中顺铂组予以单次腹腔注射顺铂(20 mg/kg,200μL),生理盐水组以等体积生理盐水替代.72h后,处死小鼠,眼球取血,同时收集肾脏组织.全自动生化分析仪检测血尿素氮(BUN)及血清肌肝(Scr)水平;HE染色检测肾组织病理学改变,实时定量PCR检测小鼠肾组织中UGHT、肾损伤分子1(阻M-I)、白细胞介素6(IL-6)、单核细胞趋化蛋白1(MCP-l)、肿瘤坏死因子α(TNF-α)的mRNA水平;免疫组织化学染色法检测肾组织中LIGHT的表达;Western blot法检测肾组织LIGHT、Bc12、BAX、细胞色素C的蛋白水平.结果与生理盐水处理的WT小鼠相比,顺铂处理WT小鼠肾组织LIGHT表达明显升高.与顺铂处理的WT小鼠相比,LIGHT^-/-小鼠顺铀诱导的肾损伤更为严重BUN、Scr升高和肾脏组织损伤更严重;且肾组织IL-6、MCP-1和TNF-α的mRNA以及BAX、细胞色素C的蛋白水平增加,Bc12蛋白水平降低.结论LIGHT在Cis-AKI中具有保护作用,可能与降低炎症因子分泌及减少细胞凋亡有关.Objective To investigate the role of LIGHT/TNFSF14(TNF superfamily protein 14)in cisplatin-induced acute kidney injury(Cis-AKI)in mice and explore the underlying mechanism.Methods Male wild-type(WT)and LIGHT gene knockout(LIGHT^-/-)C57BIV6 mice were selected and divided into four groups:saline-and cisplatin-treated WT mice,saline-and cisplatin-treated LIGHT^-/-mice.The cisplatin groups were given a single intraperitoneal injection of cisplatin(20 mg/kg,200μL),and the saline groups were injected with equal volume of normal saline(9 g/L).After 72 hours,the mice were sacrificed,blood was taken from the eyeball,and kidney tissues were collected.Blood urea nitrogen(BUN)and serum creatinine(Scr)were measured by automatic biochemical analyzer.HE staining was used to detect the histopathological changes of kidney tissues,The mRNA levels of LIGHT,kidney injury molecule 1(KIM-1),interleukin-6(1L-6),monocyte chemotactic protein 1(MCP-1),and tumor necrosis factor(TNF-α)were detected by real-time quantitative PCR.The protein levels of LIGHT,Bcl2,BAX and cytochrome C were detected by Western blot analysis or immunohistochemical staining.Results Compared with saline-treated WT mice,the expression of LIGHT in renal tissue of cisplatin-treated WT mice significantly increased.Compared with cisplatin-treated WT mice,the kidney injury in cisplatin-treated LIGHT^-/-mice was more serious;BUN and Scr increased;and the pathological damage of kidney tissue was more obvious.Moreover,the mRNA levels of IL-6,MCP-1 and TNF-α,as well as the protein levels of BAX and cytochrome C increased,while the protein levels of Bcl2 decreased.Conclusion LIGHT plays a protective role in Cis-AKI,which may be related to down-regulated secretion of inflammatory factors and decreased apoptosis.

关 键 词：与单纯疱疹病毒糖蛋白D竞争结合疱疹病毒侵入介体的淋巴毒素类似物(LIGHT) 肿瘤坏死因子超家族蛋白14(TNFSF14) 顺铂 急性肾损伤 线粒体凋亡信号通路 免疫炎症反应 

分 类 号：R692[医药卫生—泌尿科学] R392.11[医药卫生—外科学]