结缔组织生长因子在放射性肝纤维化大鼠中的动态表达及其与肝星状细胞活化的关系  

Expression of CTGF in radiation-induced hepatic fibrosis and its relationship with hepatic stellate cell activation in rats

作　　者：王云莲[1] 艾力江·吐尔逊[1] 艾尼瓦尔·艾木都拉[1] 肖蕾[1] 张月芬[1] 杨颖[1] 吴戈[1] 程纬[1] 包永星[1] 

机构地区：[1]新疆医科大学第一附属医院肿瘤中心,乌鲁木齐830054

出　　处：《中华放射医学与防护杂志》2014年第10期748-752,共5页Chinese Journal of Radiological Medicine and Protection

基　　金：新疆维吾尔自治区自然科学基金（2012211A077）

摘　　要：目的 探讨结缔组织生长因子（CTGF）在放射性肝纤维化大鼠中的动态表达及其与转化生长因子β1（TGF-β1）、α-平滑肌肌动蛋白（α-SMA）的相关性,了解CTGF与肝星状细胞（HSC）活化的关系.方法 雄性SD二级大鼠40只,用数字表法随机分为模型组（30只）和对照组（10只）.模型组大鼠右半肝接受单次6MVX射线25 Gy照射,于照射后2、4和6个月,分别用数字表法随机抽取模型组大鼠10只,对照组予以假照射后6个月,均采用HE染色观察肝组织病理变化及大鼠肝纤维化半定量积分,免疫组织化学法、RT-PCR法检测肝组织中CTGF、TGF-β1、α-SMA及其mRNA表达,并对其进行相关性分析.结果 与对照组相比,模型组于照射后2、4和6个月,肝纤维化半定量积分逐渐增加（F=25.82,P＜0.05）,模型组大鼠CTGF、TGF-β1、α-SMA蛋白的表达逐渐增多（F =55.44、16.22、121.12,P＜0.05）.对照组肝组织中,CTGF、TGF-β1、α-SMA的mRNA仅有少量表达;模型组在照射2、4和6个月CTGF、TGF-β1、α-SMA的mRNA均逐渐升高（F=177.11、133.85、217.46,P＜0.05）.相关性分析表明,大鼠肝组织中CTGF与α-SMA、TGF-β1与α-SMA均存在正相关（r =0.638、0.715,P＜0.05）.结论 CTGF的表达随着肝纤维化程度的加重而升高,在放射性肝纤维化过程中CTGF可能参与了激活TGF-β信号通路,从而促进HSC的活化与增殖.Objective To study the expression of connective tissue growth factor （CTGF） in radiation-induced hepatic fibrosis and explore its correlation with the expression of transforming growth factor β1 （TGF-β1） and α-smooth muscle actin （α-SMA） as well as the activation of hepatic stellate cells （HSC）.Methods Forty healthy male Sprague-Dawley rats were randomly divided into model group （30 rats） and control group （10 rats）.The right-half liver of rat was irradiated with a single dose of 25 Gy to establish a radiation-induced hepatic fibrosis model.Liver tissues of irradiated rats were collected at 2,4,and 6 months after irradiation.Pathomorphological changes in these liver tissues were stained with hematoxylin-eosin and observed with an optical microscope.The mRNA and protein expressions of CTGF,TGF-β1 and α-SMA were assayed by reverse transcription-polymerase chain reaction （RT-PCR） and immunohistochemistry.Results The longer the irradiation time,the degree of liver fibrosis was more serious.The expressions of CTGF,TGF-β1,α-SMA protein in the model group increased along with the time after irradiation （F =55.44,16.22,121.12,P 〈0.05）.The mRNA expressions of CTGF,TGF-β1 and α-SMA in the model group had positive correlations （r =0.638,0.715,P 〈 0.05） and were significantly higher than the control （F =177.11,133.85,217.46,P 〈0.05）.Conclusions The expression of CTGF had a positive relationship with the development of hepatic fibrosis.CTGF may be involved in the activation of TGF-β signaling pathway and thereby promotes the activation and proliferation of HSC.

关 键 词：结缔组织生长因子 转化生长因子Β1 Α-平滑肌肌动蛋白 肝纤维化 辐射 

分 类 号：R818[医药卫生—放射医学]