腹腔注射IL-33抗体对CCl4诱导小鼠肝纤维化发病的作用  

Effect of intraperitoneal injection of anti-IL-33 antibody on hepatic fibrosis induced by CCl4 in mice

作　　者：朱海军 闫琼琼 陈巍[1] 姜楠[2] 张少勇[1] 田立民[1] 孙博[1] Zhu Haijun;Yan Qiongqiong;Chen Wei;Jiang Nang;Zhang Shaoyong;Tian Limin;Sun Bo(General Surgery Department,Xi'an Central Hospital,Xi'an 710000,China;General Surgery Department,the First Affiliated Hospital of Xian JiaoTong University,Xi'an 710000,China)

机构地区：[1]西安市中心医院普外科,710000 [2]西安交通大学第一附属医院普外科,710000

出　　处：《国际免疫学杂志》2019年第3期290-295,共6页International Journal of Immunology

摘　　要：目的研究白细胞介素(interleukin,IL)-33在肝纤维化发病中的作用。方法采用C57BL/6 J小鼠建立四氯化碳(carbon tetrachloride,CCl4)诱导的小鼠肝纤维化模型,20只C57BL/6 J小鼠随机分为对照组、模型组、抗体阻断组和同型对照组,每组5只。腹腔给予IL-33抗体后,应用血清生化、酶联免疫吸附实验(enzyme-linked immunosorbent assay,ELISA)和实时定量聚合酶链式反应(real-time quantitative polymerase chain reaction,qPCR)检测肝纤维化相关指标的变化。结果与对照组相比,模型组小鼠肝组织匀浆中IL-33[(18303.1±580.4)pg/mL比(4424.2±566.9)pg/mL,P<0.05、IL-4[(707.2±83.8)pg/mL比(50.2±2.1)pg/mL,P<0.05]、IL-13[(665.8±75.7)pg/mL比(37.8±7.8)pg/mL,P<0.05]均显著升高,同时血清中谷草转氨酶(aspartate aminotransferase,AST)[(7503.4±614.2)IU/L比(44.2±5.7)IU/L,P<0.05]和谷丙转氨酶(alanine aminotransferase,ALT)[(6106.2±465.7)IU/L比(44.2±5.7)IU/L,P<0.05]亦同时升高。此外,模型组小鼠肝组织中基质金属蛋白酶(matrix metalloproteinases,MMP)2[(3.86±0.23)比(1.00±0.04),P<0.05]和MMP9[(3.36±0.19)比(1.00±0.04),P<0.05]较对照组明显升高。模型组小鼠胶原蛋白在肝中显著沉积[(2704.0±83.3)μg/mL比(1425.4±37.0)μg/mL,P<0.05]。应用抗体阻断IL-33后,模型组小鼠肝组织匀浆中IL-4[(707.2±83.8)pg/mL比(344.6±51.6)pg/mL,P<0.05]和IL-13[(665.8±75.7)pg/mL比(284.6±65.8)pg/mL,P<0.05]显著降低,血清中AST[(7503.4±614.2)IU/L比(3883.2±317.0)IU/L,P<0.05]和ALT[(6106.2±465.7)IU/L比(3684.4±169.0)IU/L,P<0.05]表达水平显著下降;肝组织中MMP2[(3.86±0.23)比(1.94±0.17),P<0.05]和MMP9[(3.36±0.19)比(2.20±0.13),P<0.05]的表达显著降低,胶原蛋白在肝中的沉积显著减轻[(2704.0±83.3)μg/mL比(1894.2±174.1)μg/mL,P<0.05]。结论细胞因子IL-33与肝纤维化的发病关系密切,阻断IL-33有可能成为一种新的治疗肝纤维化的策略。Objective To study the role of IL-33 in the pathogenesis of liver fibrosis.Methods Carbon tetrachloride(CCl4)-induced mouse liver fibrosis model was established in C57BL/6J mice Twenty C57BL/6J mice were randomly divided into control group,model group,antibody blocking group and homologous control group with 5 mice in each group..After intraperitoneal administration of interleukin(IL)-33 antibody,serum biochemistry,enzyme-linked immunosorbent assay(ELISA)and real-time quantitative polymerase chain reaction(qPCR)were used to detect liver fibrosis changes in related indicators.Results Compaired with the control group,the levels of IL-33[(18303.1±580.4)pg/mL vs.(4424.2±566.9)pg/mL,P<0.05],IL-4[(707.2±83.8)pg/mL vs.(50.2±2.1)pg/mL,P<0.05],and IL-13[(665.8±75.7)pg/mL vs.(37.8±7.8)pg/mL,P<0.05]in the liver tissue of the model group were significantly increased,while serum aspartate aminotransferase(AST)[(7503.4±614.2)IU/L vs.(44.2±5.7)IU/L,P<0.05]and alanine aminotransferase(ALT)[(6106.2±465.7)IU/L vs.(44.2±5.7)IU/L,P<0.05]levels were also elevated.The expression of matrix metalloproteinases(MMP)2[(3.86±0.23)vs.(1.00±0.04),P<0.05]and MMP9[(3.36±0.19)vs.(1.00±0.04),P<0.05]in the liver tissue of model group mice were significantly elevated and the collagen was significantly deposited[(2704.0±83.3)μg/mL vs.(1425.4±37.0)μg/mL,P<0.05].After blocking IL-33 with antibodies,IL-4[(707.2±83.8)pg/mL vs.(344.6±51.6)pg/mL,P<0.05 and IL-13[(665.8±75.7)pg/mL vs.(284.6±65.8)pg/mL,P<0.05]in liver homogenates of model group mice were significantly reduced,and the levels of AST[(7503.4±614.2)IU/L vs.(3883.2±317.0)IU/L,P<0.05]and ALT[(6106.2±465.7)IU/L vs.(3684.4±169.0)IU/L,P<0.05]in serum were significantly decreased compared with control group.The expression of MMP2[(3.86±0.23)vs.(1.94±0.17),P<0.05]and MMP9[(3.36±0.19)vs.(2.20±0.13),P<0.05]were significantly reduced in the liver tissue of model group mice,and the deposition of collagen was also significantly reduced[(2704.0±83.3)μg/mL vs.(1894.2±174.1)μ

关 键 词：肝纤维化 白细胞介素-33 

分 类 号：R575.2[医药卫生—消化系统]