小异质二聚体伴侣在大鼠肝纤维化中的动态表达及意义  

Dynamic expressions and it＇s significance of small heterodimer partner in rat models of liver fibrosis

作　　者：阳韬[1] 陆小蒟[1] 申春燕[1] 陈永平[1] 王晓东[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12期710-716,共7页Chinese Journal of Infectious Diseases

摘　　要：目的观察小异质二聚体伴侣（SHP）在大鼠肝纤维化进展过程中的动态表达变化及其意义。方法30只健康雄性SD大鼠分为对照组6只，模型组24只，模型组再按不同时间点分为2、4、6、8周4个亚组。二甲基亚硝胺（DMN）腹腔注射制备大鼠肝纤维化模型。造模后分别在不同时间点取大鼠门静脉血并留取肝脏标本，肝组织经HE和Masson染色后观察各组病理变化；RT—PCR和Western印迹法检测SHPmRNA及蛋白在造模过程中的动态变化。各组间均数比较采用单因素方差分析。结果模型组第4、6周肝纤维化明显，血清ALT、AST升高，4周时达高峰，分别为（169．2±16．2）、（193．3±31．1）U／I，；Alb逐步下降，6周时最低；各时间点与对照组比较差异均有统计学意义（FAsT一83．10，FALT一104．63，FAJI）一54．24；均P〈0．05）。造模后，SHPmRNA及蛋白在正常肝组织中都有少量表达，模型组表达显著增加，第4周达高峰，分别为0．4494_4-0．0555和1．1155-4-0．1546，第6、8周逐渐降低，且明显低于对照组；转化生长因子81（TGFβI）mRNA表达水平逐步增高，于4周时达高峰，为0．9625±0．1196，各模型组与对照组相比，差异均有统计学意义（F一25．740、171．388、118．393、94．843，均P〈0．05）。直线相关分析提示，sHPtuRNA与TGFβB1mRNA呈正相关（r一0．593，P〈0．01）。结论SHP在肝纤维化进展过程中的表达呈先升高后下降的趋势，提示可能在肝纤维化发生发展过程中发挥重要作用。Objective To observe the expressions of small heterodimer partner （SHP） in rat model of hepatic fibrosis and its role in fibrosis. Methods A total of 30 healthy male SD rats were divided into two groups： 6 rats in control group and 24 rats in model group. The model group was further divided into four subgroups which were sacrificed at different time points, 2, 4, 6 and 8 weeks after intraperitoneal injection of dimethylnitrosamine （DMN）. After establishment of the rat model, blood samples and liver tissue specimens were collected at week 2, 4, 6 and 8 respectively. The sections of liver tissue were stained with HE and Masson and then were observed under optical microscope. The expressions of SHP mRNA and protein were determined by reverse transcription polymerase chain reaction （RT PCR） and Western blot, respectively. The comparison of means among the groups was performed by univariate ANOVA. Results The hepatic fibrosis was most obvious at 4 weeks and 6 weeks after the intraperitoneal injection. In model groups, alanine aminotransferase （ALT） and aspartateaminotransferase （AST） levels gradually increased and reached a peak at week 4, which were （169.2±16.2） and （193.3±31. 1） U/L, respectively. Meanwhile, albumin level in thesignificant at all selected time points between the model group and control group （FAST--83. 10, FALT =104. 63, Fg＊b =54. 24; all P^0.05）. After modeling, the expression of SHP mRNA and protein in model group were significantly increased than those in control group, and reached a peak at week 4 （0. 4494＋_0. 0555 and 1. 1155--＋_0. 1546, respectively）, then both mRNA and protein levels decreased gradually at week 6 and 8 which obviously lower than the control group. Transforming growth factor （TGF） I31 mRNA expression level also increased gradually, reaching a peak at week 4 （0. 96254- 0.1196）, and the differences between model subgroups and control group were statistically significant （F= 25. 740, 171. 383, 118. 393 and 94. 343; all P≯0

关 键 词：RNA 信使 转化生长因子Β1 二甲基亚硝胺 肝硬化 实验性 疾病模型 动物 

分 类 号：R285.5[医药卫生—中药学]