目的:研究白细胞介素-6（IL-6）在急性肝损伤发生、发展过程中的作用。方法:将12只无特定病原体C57BL/6雄性小鼠随机分为对照组和模型组，每组各6只，对照组和模型组分别尾静脉注射等体积磷酸盐缓冲液（PBS）和刀豆蛋白A（ConA）（按10 mg/kg注射）。6 h收取标本进行肝组织HE染色、转氨酶测定以确定模型诱导成功。采用荧光定量PCR（qPCR）筛选白细胞介素（IL）-6、IL-17、IL-1β及干扰素（IFN）γ、肿瘤坏死因子α的表达，酶联免疫吸附法测定IL-6和IFNγ表达情况。后分别设立急性肝损伤对照组和IL-6中和抗体组各3只，等体积PBS或IL-6中和抗体（100 μg /只）提前30 min尾静脉注射，再尾静脉注射ConA（10 mg/kg），6 h取眼血和肝组织，对肝组织进行HE染色和血清丙氨酸转氨酶（ALT）测定。对数据比较采用独立样本均数的n t检验。n 结果:模型组ALT和天冬氨酸转氨酶（AST）显著高于对照组[ALT：（2 618.99±188.08）U/L与（43.34±5.02）U/L，n t = -13.69，n P = 0.001；AST：（942.48±150.44）U/L与（57.80±4.84）U/L，n t = -5.878，n P = 0.01]。肝组织HE染色显示肝细胞索结构紊乱，肝细胞胞质淡染，大片坏死灶逐渐形成，伴淋巴细胞浸润，小鼠急性肝损伤模型成功建立。模型组IL-6、IFNγ mRNA和蛋白水平与对照组相比，表达明显上调。模型组IL-6 mRNA表达量是对照组的73.7倍（n t = -6.218，n P < 0.001），血清IL-6表达量也高于对照组[（18 537.02±92.57）pg/ml与（9.51±1.01）pg/ml， n t = -199.782，n P < 0.001]。IFNγ mRNA是对照组的108.4倍（ n t = -4.413，n P = 0.003），模型组血清IFNγ浓度也高于对照组[（12 068.30±288.43）pg/ml与（25.97±3.52）pg/ml，n t = -41.748，n P < 0.001]。其中IL-6水平增加最明显，提示其可能参与肝损伤的发生、发展过程。尾静脉注射IL-6中和抗体，IL-6中和抗体组小鼠ALT水平较急性肝损伤对照组明显下调[（167.41±47.80）U/L与（1 520.34±190.21）U/L， n t = 6.899，n P = 0.015]。肝组织HE染色显示阻断血清IL-6后，肝细胞坏死明显减轻，坏死灶数量减少。免疫组织化学结果显示IL-6中和抗体组活化的caspase3表达减少，肝细胞凋亡减少。n 结论:中和IL-6可明显减轻ConA引起的急性肝损伤。“,”Objective:To study the role of interleukin 6 (IL-6) in the occurrence and development of acute liver injury.Methods:Twelve C57BL/6 male mice without specific pathogens were randomly divided into a control group and an acute liver injury model group, with six mice in each group. Control and model group were injected with an equal volume (dosage of 10 mg/kg) of phosphate-buffered saline (PBS) and concanavalin A (ConA) into the tail vein, respectively. Samples were collected at 6 h for liver HE staining. Transaminase assay was used to determine the success of the induction model. The expression of IL-6, IL-17, IL-1β, interferon (IFN) γ and tumor necrosis factor α were screened by quantitative fluorescence PCR (qPCR). The expressional condition of IL-6 and IFNγ were measured by enzyme-linked immunosorbent assay (ELISA). Subsequently, three control groups and three IL-6 neutralizing antibody groups were established for acute liver injury, respectively. Equal volumes of PBS or IL-6 neutralizing antibody (100 μg/body) were injected prior 30 minutes, followed by injection of ConA (10 mg/kg) into the tail vein. Blood sampled from eye and liver tissue were fetched at 6 h. Liver tissues were stained with HE and serum alanine aminotransferase (ALT) was determined. An independent sample T-test was used for data comparison.Results:Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) of the model group was significantly higher than control group [ALT: (2 618.99 ± 188.08) U/L and (43.34 ± 5.02) U/L, n t = -13.69, n P = 0.001; AST: (942.48 ± 150.44) U/L and (57.80 ± 4.84) U/L, n t = -5.878, n P = 0.01]. Liver HE staining showed that the structure of hepatocyte cord was disordered, the cytoplasm of hepatocyte was lightly stained, and large necrotic foci were gradually formed, accompanied by lymphocyte infiltration, and then a mouse model of acute liver injury was successfully established. Protein levels of IL-6 and IFN, and mRNA of the model group were significantly up-regulated, as compared to control group. IL-6 mRNA expression of the model group was increased 73.7 times that of the control group (n t =-6.218, n P < 0.001), and the serum IL-6 expression level was also higher than that of the control group (18 537.02 ± 92.57) pg/ml ( n t = -199.782, n P < 0.001). IFNγ mRNA was 108.4 times higher than that of the control the group ( n t = -4.413, n P = 0.003), and serum IFNγ concentration of the model group was also higher than the control group (12 068.30 ± 288.43) pg/ml (n t = -41.748, n P < 0.001). Among them, IL-6 level was obviously increased, suggesting that it could participate in the occurrence and development of liver injury. IL-6 neutralizing antibody was injected into the tail vein. ALT level of IL-6 neutralizing antibody was significantly lower than acute liver injury control group [(167.41 ± 47.80) U/L and (1 520.34 ± 190.21) U/L, n t = 6.899, n P = 0.015]. Liver tissue HE staining showed that hepatocyte necrosis and the number of necrotic foci was significantly alleviated after blocking serum IL-6.Immunohistochemical results showed that the expression of activated caspase3 and hepatocyte apoptosis in the IL-6 neutralizing antibody group was decreased.n Conclusion:Neutralizing IL-6 can significantly reduce acute liver injury caused by concanavalin A.