摘要
目的研究白细胞介素5(IL-5)对CCl4诱导的小鼠急性肝损伤(ALI)的保护作用。方法利用腹腔注射不同剂量CCl4,诱导小鼠ALI模型,并于损伤后24、36、48、72 h通过ELISA检测血清中丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)、IL-5的含量;计算血清中IL-5水平与ALT、AST之间的相关系数;在CCl4造模前24 h给小鼠腹腔注射重组IL-5蛋白100μg/kg,于损伤后24、36、48、72 h检测血清中ALT和AST水平以及肝组织中Caspase-3的活性;对肝组织进行HE、BrdU或Ki67免疫组化染色,统计肝组织坏死面积以及BrdU和Ki67阳性细胞比例。结果CCl4造模后24 h,小鼠血清中IL-5水平升高,并与肝损伤程度呈正相关;与对照组相比,IL-5组小鼠在CCl4造模24 h后ALT减少约63.2%(P<0.0001)、AST减少约59.6%(P<0.0001);CCl4造模后36 h小鼠肝坏死面积减少约45.8%(P<0.05);CCl4造模后48 h肝组织中Caspase-3活性下降64.3%(P<0.01);在CCl4造模后36、48 h小鼠肝BrdU、Ki67阳性细胞数目显著升高(P<0.01)。结论IL-5能改善CCl4介导的ALI以及促进肝损伤的修复过程。
Objective To investigate the protective effect of interleukin 5(IL-5)on CCl4-mediated acute liver injury(ALI).Methods A mouse model of ALI was constructed via intraperitoneal injection with different doses of CCl4.After24,36,48,and 72 hours,ALT,AST,and IL-5 in serum were measured by ELISA determine the relationship between ALT,AST and IL-5.Twenty-four hours before CCl4 was administered,mice were intraperitioneally injected with recombinant mouse IL-5 protein(100μg/kg)or vehicle control.After 24,36,48,and 72 hours,the content of ALT,AST in serum and Caspase-3 activity in the liver were measured.Liver sections were stained with HE,anti-BrdU or Ki67.The necrotic area and percentage of positive cells were calculated.Results Twenty-four hours after administration of CCl4,the content of IL-5 in serum was elevated and positively correlated with the degree of liver injury.Compared with vehicletreated mice,ALT and AST in IL-5 treated mice were reduced approximately by 63.2%(P<0.0001)and 59.6%(P<0.0001)respectively.36 hours after CCl4 was administered,the necrotic area of the mouse liver was reduced by about45.8%(P<0.05).48 hours after CCl4 was administered,Caspase-3 activity in the liver was decreased by about 64.3%(P<0.01).36 and 48 hours after CCl4 was administered,the percentage of BrdU and Ki67-positive cells in the liver was significantly increased(P<0.01).Conclusion This study showes that IL-5 can alleviate CCl4-mediated ALI and accelerate liver regeneration.
作者
付宗恒
雷达鑫
陈慧
翟华立
詹轶群
葛志强
杨晓明
于淼
FU Zong⁃heng;LEI Da⁃xin;CHEN Hui;ZHAI Hua⁃li;ZHAN Yi⁃qun;GE Zhi⁃qiang;YANG Xiao⁃ming;YU Miao(School of Chemical Engineering and Technology,Tianjin University,Tianjin 300072,China;State Key Laboratory of Proteomics,Institute of Lifeomics,Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China)
出处
《军事医学》
CAS
北大核心
2020年第7期493-499,共7页
Military Medical Sciences
基金
蛋白质组学国家重点实验室项目(SKLP-K201404)