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D-半乳糖与L-谷氨酸诱导树鼩肝组织损伤

D-galactose and L-glutamic acid induced liver tissue injury in tree shrews
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摘要 目的探究D-半乳糖与L-谷氨酸对树鼩肝组织损伤及机制。方法雄性树鼩随机分为4组:对照组(CT组)、D-半乳糖组(D组)、L-谷氨酸组(G组)、D-半乳糖组+L-谷氨酸组(D+G组),每周称量体重、计算存活率。给药8周后,心脏采血处死树鼩,4%多聚甲醛灌注固定肝,进行HE和免疫组织化学染色,检测TLR2、NF-κB和P-gp表达。结果相对于第1周,第8周D+G组树鼩体重下降。G组、D组、D+G组生存率下降,肝细胞变性、水肿、坏死、炎性细胞浸润、中央静脉、门静脉、分支胆管扩张,其中D+G组最严重。相对于CT组,D组、G组和D+G组的TLR2(P<0.05)、NF-κB(P<0.01)和P-gp(P<0.01)表达均升高;在3个处理组中,D+G组的TLR2(P<0.05)、NF-κB(P<0.01)和P-gp(P<0.01)表达显著高于D组和G组。结论D-半乳糖、L-谷氨酸单独或联合给药均可引起树鼩肝组织损伤,联合给药损伤更严重。其机制可能涉及TLR2/NF-κB通路激活,同时P-糖蛋白代偿性增加。 Objective To investigate the liver injury mechanism induced by D-galactose and L-glutamic acid in tree shrews.Methods Male tree shrews were randomly divided into four groups:the control(CT),D-galactose(D),Lglutamic acid(G)and D-galactose combined with L-glutamic acid(D+G)groups.The weight and survival rates were recorded weekly.Medication was administered for 8 weeks,then the tree shrews were sacrificed.Their livers were perfused with 4%paraformaldehyde for hematoxylin and eosin and immunohistochemical staining to detect TLR2,NF-κB and Pglycoprotein(P-gp)expressions.Results The body weights in the D+G group were lower at week 8 than at week 1.The survival rates in the G,D and D+G groups decreased compared with that of the CT group.Hepatocytic degeneration,edema,necrosis and inflammatory cell infiltration occurred in addition to dilatation of the central and portal vein and the branch bile duct in the livers of the G,D and D+G groups.Compared with CT group,the expressions of TLR2(P<0.05),NF-κB(P<0.01)and P-gp(P<0.01)were significantly increased in the D,G and D+G groups and were significantly higher in the D+G group than in the D or G groups.Conclusions D-galactose and/or L-glutamic acid induce liver tissue injury in tree shrews,which may be involved in activating TLR2/NF-κB signaling and P-gp.
作者 陆姜利 郭玉倩 钱忠义 角建林 梁张 郑红 LU Jiangli;GUO Yuqian;QIAN Zhongyi;JIAO Jianlin;LIANG Zhang;ZHENG Hong(Department of Laboratory Animal Science,Kunming Medical University,Kunming 650500,China;Experimental Teaching Center of Basic Medical College,Kunming Medical University,Kunming 650500;Technology Transfer Centers,Kunming Medical University,Kunming 650031)
出处 《中国实验动物学报》 CAS CSCD 北大核心 2020年第1期81-88,共8页 Acta Laboratorium Animalis Scientia Sinica
基金 云南省应用基础研究计划项目(2017FE468-014,2017FE468-016) 云南省教育厅科学研究项目(2018Y048) 昆明医科大学创新基金项目(2019S093).
关键词 肝组织损伤 L-谷氨酸 D-半乳糖 TLR2/NF-κB信号途径 P-糖蛋白 liver tissue injury L-glutamic acid D-galactose TLR2/NF-κB signal P-glycoprotein
作者简介 陆姜利(1992—),女,在读硕士研究生,研究方向:药理学。Email:1311345248@qq.com;通信作者:郑红(1969—),女,教授,博士,研究方向:比较医学。Email:847255170@qq.com;通信作者:梁张(1966—),女,副教授,硕士,研究方向:药学。Email:ynlml-z@163.com
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