JNK信号通路在脂多糖诱导的小鼠急性肝损伤中的表达研究  

Expression of JNK signal pathway in mice with acute liver injury induced by lipopolysaccharide

作　　者：覃春美 苏松[2] 魏晓[1] 龚财判 吴蔚桦[1] 欧三桃[1] 

机构地区：[1]泸州医学院附属医院肾内科,四川泸州646000 [2]泸州医学院附属医院肝胆外科,四川泸州646000

出　　处：《中国现代医学杂志》2015年第20期7-11,共5页China Journal of Modern Medicine

基　　金：四川省科技厅资助课题(No:2014JY0068)

摘　　要：目的观察脂多糖(LPS)诱导的小鼠急性肝损伤模型肝组织中JNK信号通路(p-JNK和p-c-Jun)的表达变化,以探讨JNK信号通路在急性肝损伤中的作用和意义。方法将小鼠随机分为对照组和LPS腹腔注射诱导的急性肝损伤模型组,分别于给药后1、2、4和30 h处死小鼠,检测血清丙氨酸转氨酶(ALT)、天冬氨酸转氨酶(AST)水平。HE染色观察肝脏组织的病理变化。免疫组织化学染色、Western blot检测肝脏组织p-JNK和p-c-Jun蛋白的表达部位及强度。酶联免疫吸附(ELISA)法检测血清肿瘤坏死因子-α(TNF-α)及白介素1β(IL-1β)水平。结果 LPS腹腔注射后可导致小鼠血清ALT及AST水平升高,肝组织病理损伤进行性加重,p-JNK和p-c-Jun在肝细胞核大量表达。与对照组比较,模型组小鼠p-JNK和p-c-Jun蛋白水平于1 h时显著升高并达峰值,此后逐渐下降,血清TNF-α及IL-1β水平在注射LPS 1 h后明显升高,4 h达峰值后逐渐下降。结论 JNK信号通路的活化在LPS诱导的小鼠急性肝损伤的发病过程中起重要作用,JNK信号通路可通过诱导TNF-α和IL-1β的表达参与急性肝损伤的发生与发展。[Objective] To observe the expression of c-Jun amino-terminal kinase （JNK） signal pathway （p-JNK and p-c-Jun） in mouse models with lipopolysaccharide （LPS）-induced acute liver injury and to explore the effects and the significance of JNK signal pathway in acute liver injury. [Methods] Mice were randomly divided into control group and acute liver injury model group induced by intraperitoneal injection of LPS. The mice were sacrificed at 1, 2, 4 and 30 h and the serum alanine transaminase （ALT） and aspartate transaminase （AST） were measured. The pathologic changes in the liver were observed in HE sections. Immunohistochemistry （IHC） and Western blot were applied to detect the expressions of p-JNK and p-c-Jun in liver respectively. Serum level of TNF-α and IL-1β was determined by ELISA. [Results] The level of ALT and AST was significantly increased after LPS injection and the pathological damages of the liver tissues showed a continual worsening trend. Strong expressions of p-JNK and p-c-Jun in the hepatocyte nuclei were detected in the model group compared with the control group, which reached the peak at 1 h and then gradually decreased. The level of TNF-α and IL-1β obviously increased in the model group and reached the peak 4 hafter the LPS injection followed by a gradual decrease role in the pathogenesis of acute liver injury induced [Conclusions] JNK signal pathway plays an important by LPS. JNK signal pathway may mediate the occurrenee and development of acute liver injury by triggering the expressions of TNF-α and 1L-1β.

关 键 词：脂多糖 急性肝损伤 C-JUN氨基末端激酶 信号通路 

分 类 号：R575[医药卫生—消化系统]