摘要
目的观察胍丁胺（AGM）对脂多糖（LPS）诱导急性肝损伤的保护作用，并探讨其作用机制。方法将60只成年C57BL／6小鼠按随机数字表法分为对照组（20只，腹腔注射磷酸盐缓冲液10mg／kg）、模型组（20只，腹腔注射LPS10mg／kg）和胍丁胺组（20只，腹腔注射LPS10mg／kg和胍丁胺200mg／ks），各组于制模后6h和24h分别处死10只小鼠，采集血和肝组织制备组织匀浆。制模后6h采用酶联免疫吸附试验（ELISA）检测血清和肝组织中肿瘤坏死因子-α（TNF-α）、白细胞介素（IL-1β、IL-6）的含量；制模后24h用全自动生化分析仪测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）及总胆红素（TBil）水平；制模后6h采用蛋白质免疫印迹试验（Western blotting）检测肝细胞核内核转录因子-κB（NF—κB）p65的含量；制模后24h观察肝组织病理学改变。结果制模后6h，模型组小鼠表现为精神萎靡、蜷缩少动、禁饮食水；胍丁胺组小鼠精神和活动明显好于模型组。胍丁胺治疗后能有效降低LPS所致急性肝损伤小鼠血清中TNF—α（μμg／L：296．3±42．5比627．2±81．3，t=7．327，P=0．002）、IL-1β（μg／L：109．1±12．3比264．2±18．8，t=11．958，P=0．001）、IL-6（mg／L：11．4±1．9比23．6±2．5，t=6．729，P=0．003）、ALT（U／L：107．94±8.5比189．9±13．6，t=8．856，P=0．001）、AST（U／L：347．4±24．9比716．8±60．4，t=9．793，P=0．001）、TBil（μmol／L：8．3±0．9比10．6±0．5，t=3．869，P=0．018）的含量，减少肝组织TNF—α（ng／g：287．4±32．5比461．5±31．4，t=6．673，P=0．003）、IL—1β（pg／g：146．7±13．5比351．6±28．7，t=11．190，P=0．001）和核内NF—κBp65蛋白表达[NF—κBp65／核内参（灰度值）：0．515±0．060比0．853±0．080，t=5．849，P=0．0043。LPS注射后24h肝脏出现明显病理改变，如肝细胞肿胀、坏死、充�
Objective To observe the effect of agmatine （AGM） on lipopolysaccharide （LPS）-induced acute hepatic injury in mice, and to explore its related mechanism. Methods Sixty C57BL/6 mice were randomly divided into control group （n=20, with intra-peritoneal injection of phosphate buffer saline 10 mg/kg）, model group （n=20, with intra-peritoneal injection of LPS 10 mg/kg）, and AGM group （n=20, with intra-peritoneal injection of LPS 10 mg/kg and AGM 200 mg/kg）. Ten mice in each group were sacrificed at 6 hours and 24 hours, respectively, after modeling, blood samples were collected for the determination of tumor necrosis factor-α （TNF-α） and interleukin （IL-1β and IL-6） by enzyme linked immunosorbent assay （ELISA） at 6 hours after modding, and for determination of alanine aminotransferase （ALT）, aspartate transaminase （AST） and total bilirubin （TBil） by automatic biochemistry analyzer at 24 hours after modeling. Hepatic homogenate was also collected for determining the endonuclear nuclear factor-κB （NF-κB） p65 by Western blotting at 6 hours after modeling, and for observation of pathological changes at 24 hours after modeling. Results At 6 hours after modeling, the mice in model group became lethargic and quiet, and their food and water assumption was reduced, but AGM was found to be able to greatly improve the general status of animals in AGM group. AGM was found to lower the contents of serum TNF-α （ μg/L： 296.3 ± 42.5 vs. 627.2 ± 81.3, t=7.327, P=0.002）, IL-1β （μg/L： 109.1 ± 12.3 vs. 264.2± 18.8, t=11.958, P=0.001）, IL-6 （mg/L： 11.4±1.9 vs. 23.6±2.5, t=6.729, P=0.003）, ALT （U/L： 107.9 ± 8.5 vs. 189.9 ± 13.6, t=8.856, P=0.001）, AST （U/L： 347.4± 24.9 vs. 716.8 ± 60.4, t=9.793, P=0.001 ） and TBil （ μmol/L： 8.3 ± 0.9 vs. 10.6 ± 0.5, t=3.869, P=0.018） in mice with acute hepatic injury induced by LPS. AGM also depressed TNF-α （ng/g： 287.4 ± 32.5 vs. 461.5 ± 31.4, t=6.673, P=0.003）, IL-1β （pg/g： 146.7 ± 13.
出处
《中华危重病急救医学》
CAS
CSCD
北大核心
2013年第12期720-724,共5页
Chinese Critical Care Medicine
基金
国家重点基础研究发展计划（973）项目（2012CB518102）
关键词
胍丁胺
脂多糖
急性肝损伤
炎症因子
Agmatine
Lipopolysaccharide
Acute hepatic injury
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