敲除TSP-1对小鼠急性肝损伤保护作用的机制  

The protective mechanism of TSP-1 knockout on acute liver injury in mice

作　　者：吴敏[1] 冯伟珂 占一姗[1] 王剑巧 曾金娣 李科浩 张守华[1] 陶强[1] 占敏 WU Min;FENG Wei-ke;ZHAN Yi-shan;WANG Jian-qiao;ZENG Jin-di;LI Ke-hao;ZHANG Shou-hua;TAO Qiang;ZHAN Mi(Department of General Surgery,Jiangxi Provincial Children's Hospital,Nanchang 330038,Jiangxi,China;不详)

机构地区：[1]江西省儿童医院普外科,江西南昌330038 [2]九江学院附属医院,江西九江332000 [3]井冈山大学附属医院,江西吉安343000

出　　处：《广东医学》2024年第2期152-158,共7页Guangdong Medical Journal

基　　金：国家自然科学基金资助项目(81960101);江西省卫生健康委科技计划项目(202211240,202210961)。

摘　　要：目的研究敲除血小板反应蛋白1(thrombospondin 1,TSP-1)在四氯化碳(CCl_(4))所致小鼠急性肝损伤中的保护作用。方法选取C57BL/6J小鼠16只,TSP-1基因敲除小鼠8只:C57BL/6J小鼠分为WT组和WT+CCl_(4)组,TSP-1基因敲除小鼠为TSP-1^(-/-)+CCl_(4)组;WT+CCl_(4)和TSP-1^(-/-)+CCl_(4)组给予0.5 mL CCl_(4)+9.5 mL/kg橄榄油进行腹腔注射建立急性肝损伤模型,WT组注射橄榄油10 mL/kg作为对照。通过HE染色以及血清中丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白细胞介素-6(IL-6)和肿瘤坏死因子-α(TNF-α)观察各组小鼠肝脏损伤情况及炎症反应程度;同时检测肝组织丙二醛(MDA)和谷胱甘肽(GSH)的含量并通过免疫组化和TUNEL检测凋亡的变化。结果敲除TSP-1对CCl4诱导的急性肝损伤具有明显的改善作用,表现为血清AST、ALT、IL-6和TNF-α的降低和肝细胞坏死的减少,以及降低MDA含量和升高GSH含量,减少肝组织中凋亡及caspase-3的表达。结论敲除TSP-1对CCl_(4)诱导的小鼠急性肝损伤具有明显的保护作用,其机制可能与抑制炎症、氧化应激和细胞凋亡相关。Objective To study the protective effect of TSP-1 knockout on acute liver injury induced by carbon tetrachloride in mice.Methods Sixteen C57BL/6J mice and eight TSP-1 gene knockout mice were selected for the study.The C57BL/6J mice were divided into two groups,WT group and WT+CCl_(4) group,while the TSP-1 gene knock-out mice were grouped as TSP-1^(-/-)+CCl_(4) group.The WT+CCly and TSP-1^(-/-)+CCl_(4) groups received intraperitone-al injection of 0.5 mL CCl_(4)+9.5 mL/kg olive oil to establish an acute liver injury model,whereas the WT group was given an intraperitoneal injection of 10 mL/kg olive oil as the control.The extent of liver damage and inflammatory response in each group of mice was observed through HE staining and measurement of serum levels of ALT,AST,IL-6,and TNF-Q.Additionally,the content of MDA and GSH in liver tissues was determined,and apoptosis was detected by immuno-histochemistry and TUNEL staining.Results Knockout of TSP-1 significantly ameliorated acute liver injury induced by CCl_(4),as evidenced by decreased serum levels of AST,ALT,IL-6,and TNF-α,reduced hepatocyte necrosis,de-creased MDA content,increased CSH content,decreased apoptosis,and downregulation of caspase-3 expression in liver tissues.Conclusion Knockout of TSP-1 exerts a marked protective effect against CCl_(4)-induced acute liver injury in mice,possibly through its involvement in the inhibition of inflammation,oxidative stress,and apoptosis.

关 键 词：血小板反应蛋白1 四氯化碳 急性肝损伤 

分 类 号：R575[医药卫生—消化系统] R363[医药卫生—内科学]