大麻素受体1和细胞外信号调节激酶在肝纤维化小鼠肝组织中的表达及意义  

CB1 and ERK gene expression in liver tissue of rats with experimental hepatic fibrosis

作　　者：杨莉[1] 赵连英[2] 刘彦超[1] 叶立红[1] 戴二黑[1] 

机构地区：[1]石家庄市第五医院,石家庄050021 [2]河北工程大学附属医院,邯郸056002

出　　处：《临床肝胆病杂志》2012年第9期681-684,共4页Journal of Clinical Hepatology

基　　金：中国肝炎防治基金会王宝恩肝纤维化研究基金项目(20080013);河北省卫生厅指令性课题(08190)

摘　　要：目的研究大麻素受体1(CB1)mRNA在肝纤维化形成过程中表达的变化,从基因转录水平探讨其与细胞外信号调节激酶(ERK)的关系。方法采用10%四氯化碳腹腔注射制备肝纤维化模型,分别于造模第2、4、6、8周留取小鼠的肝组织及血清。通过病理对肝组织进行形态学观察,荧光定量RT-PCR检测CB1 mRNA和ERK mRNA水平,生化法检测血清中ALT和AST的含量,放射免疫法检测血清中透明质酸(HA)的含量。结果与正常对照组相比,各模型组小鼠肝组织中CB1 mRNA和ERK mRNA含量显著升高(P<0.05),而且随造模时间的延长,CB1 mRNA和ERK mRNA含量亦逐渐增高,各组之间差异有统计学意义(P<0.05)。各模型组小鼠血清中ALT、AST及HA的水平随造模时间延长而不断升高,各组间差异具有统计学意义(P<0.05)。CB1 mRNA的含量不但与血清中ALT、AST、HA的含量呈显著正相关(r=0.741、0.763、0.769,P均<0.01),而且与肝组织中ERK mRNA含量也呈显著正相关(r=0.789,P均<0.01)。结论CB1可能通过激活ERK,以ERK通路诱导肝星状细胞(HSC)增殖,促进肝纤维化的形成。Objective To evaluate the roles of the cannabinoid receptor type 1 （CB1） and extracellular -signal regulated kinase （ERK） in hepatic fibrosis. Methods A rat model of hepatic fibrosis was generated by intraperitoneal injection of 10% carbon tetraehloride. Liver tissues and serum samples were collected at post - injection weeks 2, 4, 6, and 8. Histopathological changes were detected by hematoxylin - eosin staining. Changes in mRNA levels of CB1 and ERK were determined by quantitative reverse transcription - polymerase chain reaction. Bio- chemical assays were used to detect changes in serum alanine aminotransferase （ALT） and aspartate aminotransferase （AST） levels, and radio- immunoassay was used to determine changes in serum hyaluronic acid （HA） level. Results Compared with the uninduced, non - fibrotic control group, the mRNA levels of CB1 and ERK were significantly higher in the fibrotic group at all times examined （all P 〈 0.05 ）. Moreover, the levels of CB1 and ERK mRNA, and serum ALT, AST and HA significantly increased over time （ all factors, all time points P 〈 0. 05 ）. The CB1 mRNA level in liver tissue was correlated with the levels of serum ALT, AST, and HA （ r =0.741,0.763, 0. 769, respectively; all P 〈 0.01 ） and with ERK mRNA in liver tissue （ r = 0.789, P 〈 0.01 ）. Conclusion CB1 may promote the activation of ERK in rats with hepatic fibrosis, and may induce hepatic stellate cell proliferation via ERK signal transduction to promote progression of liver fibrosis.

关 键 词：受体 大麻酚 CB1 细胞外信号调节MAP激酶素 肝硬化 

分 类 号：R285.5[医药卫生—中药学]