Notch／Jagged信号通路在肝纤维化大鼠模型中的动态表达及意义  

Dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis

作　　者：叶超[1] 陈永平[1] 金晓芝[1] 程瑗[1] 戴志娟[1] 林镯[1] 

机构地区：[1]温州医学院附属第一医院感染内科,325000

出　　处：《中华传染病杂志》2011年第2期81-86,共6页Chinese Journal of Infectious Diseases

基　　金：基金项目：中国肝炎防治基金会王宝恩肝纤维化研究基金项目（20080017）

摘　　要：目的探讨Notch／Jagged通路在肝纤维化大鼠模型中的动态表达及意义。方法健康雄性SD大鼠42只分为健康对照组和模型组，模型组再按造模后不同时间分为4d、1周、2周、4周、6周、8周等6个亚组，每组6只。模型组腹腔注射二甲基亚硝胺（DMN）诱导大鼠肝纤维化模型，测定不同时间点血清ALT、AST、Alb和HA的变化；肝组织经HE、Masson染色，光学显微镜下观察；采用RT-PCR和免疫组织化学法检测不同时间点肝脏Notch-1、Jagged-1mRNA和蛋白表达。各组间均数比较采用单因素方差分析。结果DMN腹腔注射成功诱导大鼠肝纤维化模型，表现为造模4周后肝小叶结构破坏或消失，汇管区或中央静脉有较粗大的纤维条索包绕肝组织形成假小叶。ALT、AST、Alb、HA均于造模后4d开始上升，并于4周达到最高峰，且明显高于健康对照组（F值分别为83．10，104．63，54．24，203．81；均P〈0．05）。Notch-1、Jagged-1mRNA及蛋自在正常肝组织中仅少量表达，模型组表达显著增加（F值分别为282．44，369．14，374．17，256．14；均P〈0．01），且与肝纤维化分级和转化生长因子B1（TGFβ1）的表达量呈正相关（r分别为0．821，0．917，0．767，0．844；P％0．01）。结论Notch／Jagged信号通路可能参与肝纤维化的发生，并与肝纤维化的发展过程和严重程度密切相关。Objective To explore the dynamic expressions and the significance of Notch/Jagged signal pathway in rat model of hepatic fibrosis. Methods A total of 42 healthy male SD rats were randomly divided into normal control group （n = 6） and model group （n = 36）. The model group was further divided into six subgroup according to different time points： subgroups of 4 days, 1, 2, 4, 6 and 8 weeks with six rats in each subgroup. The rat model of hepatic fibrosis was induced by dimethylnitrosamine （DMN）. The serum levels of alanine aminotransferase （ALT）, aspertate aminotransferase （AST）, albumin （Alb） and hyaluronie acid （HA） were detected dynamically after 4 days, 1,2,4,6 and 8 weeks of injection. The liver tissues were observed under optical microscope after HE and Masson staining. Notch-i, Jagged-1 mRNA and protein in liver were detected by reverse transcriptase polymerase chain reaction （RT-PCR） and immunohistochemistry. The comparison of means among groups was done by univariate ANOVA. Results The hepatic fibrosis model was successfully induced by DMN injection and pseudotobules were found after 4 weeks of injection. The serum levels of ALT, AST, Alb and HA were all increased after 4 day of injection and peaked at week 4 which were all significantly higher than those in control group （F= 83.10, 104.63, 54.24,203. 81, respectively; all P〈0.05）. The expressions of Notch-l, Jagged-1 mRNA and protein in model group were all significantly increased than those in control group （F=282.44, 369.14, 374. 17, 256. 14, respectively;P〈0. 01）. And the expressions of Notch-1, Jagged-1 were closely correlated with the hepatic fibrosis stages and transforming growth factor β1 （TGF01） expression （r=0. 821, 0. 917, 0. 767,0. 844, respectively; P〈0. 01）. Conclusions The Notch/Jagged pathway may participate in the development of hepatic fibrosis, which is closely correlated with the progression and severity of liver fibrosis.

关 键 词：肝硬化 疾病模型 动物 大鼠 Sprague—Dawley 信号传导 转化生长因子Β1 

分 类 号：R285.5[医药卫生—中药学]