脑肠肽通过抗炎抗氧化作用发挥酒精性肝损伤的保护作用  

Protective effects of ghrelin against alcoholic induced liver injury in mice via anti-inflammation and anti-oxidative stress

作　　者：孙梦雯 胡世莲 殷实 严光 

机构地区：[1]安徽医科大学附属省立医院老年病科安徽省老年病研究所,安徽合肥230001

出　　处：《中国药理学通报》2014年第10期1452-1456,共5页Chinese Pharmacological Bulletin

基　　金：安徽省国际科技合作计划(No 11030603025)

摘　　要：目的研究脑肠肽对小鼠酒精性肝损伤的保护作用。方法采用4周5%酒精饲料喂饲加5 g·kg-1的高剂量酒精灌胃诱导酒精性肝损伤模型,用分光光度法检测血清中ALT、AST和肝匀浆MDA、SOD、GSH-Px含量;Real-time PCR法检测肝脏中炎症细胞因子TNF-α、IL-1β、IFN-γ、IL-6和MCP-1的表达。HE染色检测肝脏病理改变。结果这种慢性酒精喂饲+单剂量大剂量酒精灌胃模式可明显诱导酒精性肝损伤,可导致明显的转氨酶升高、脂肪肝和炎症浸润。给予脑肠肽(5、10、20μg·kg-1)ip后可明显降低酒精性肝损伤小鼠增高的血清ALT、AST活性,改善酒精肝病理改变和炎症浸润;并能减少肝匀浆MDA含量,使降低的肝匀浆SOD活性升高;降低酒精性肝损伤小鼠肝脏的炎症细胞因子TNF-α、IL-1β、IFN-γ、IL-6和MCP-1的mRNA表达。结论脑肠肽对小鼠酒精性肝损伤具保护作用,其机制与抗氧化和抑制炎症作用有关。Aim To investigate the effects of ghrelin on alcohol-induced liver injury. Methods The alcoholic liver injury mouse model was induced by chronic etha-nol feeding （ 4-week ad libitum oral feeding with the ethanol liquid diet） plus a single binge ethanol （5 g· kg-1 ） feeding. The level of alanine aminotransferase （ALT）, aspartate aminotransferase （AST） in serum, malondiadehyde （ MDA ） content, superoxide dis-mutase （SOD） and glutathione peroxidase （GSH-Px） activities in liver homogenate were assayed by spectro-photometer. Hepatic pathological examination was ob-served by HE staining. The mRNA expression of proin-flammatory cytokines including TNF-α, IL-1β, IFN-γ, IL-6 and MCP-1 in the liver was measured by real-time PCR method. Results This chronic-plus-single-binge high dose ethanol feeding synergistically induced liverinjury, inflammation and fatty liver change. Treatment with Ghrelin （ 5 , 10 , 20 μg · kg-1 ） significantly de-creased the enhanced level of transaminase （ ALT, AST） in serum, improved the pathologic change in liv-er, and reduced the infiltration of inflammatory cells induced by alcohol administration. Ghrelin also de-creased MDA content and increased the reduced SOD and GSH-Px level in liver homogenate. Furthermore, ghrelin decreased inflammatory cytokines mRNA ex-pression including TNF-α, IL-1β, IFN-γ, IL-6 and MCP-1 in the liver. Conclusion Ghrelin has protec-tive effects against alcoholic liver injury in mice via in-hibiting inflammation and suppressing oxidative stress.

关 键 词：脑肠肽 酒精性肝损伤 氧自由基 TNF-Α IL-1Β MCP-1 

分 类 号：R-332[医药卫生] R322.47