缺氧诱导因子-1α在布-加综合征大鼠模型肝组织的表达及意义  

Expression and significance of hypoxia inducible factor - 1α in Budd - Chiari syndrome model in rats

作　　者：李路豪 党晓卫[1] 李林[1] 李海[1] 徐韶凯 付坤坤 刘优优[1] 许培钦[1] 

机构地区：[1]郑州大学第一附属医院肝胆胰外科河南省布-加综合征诊疗中心,450052

出　　处：《中华实验外科杂志》2018年第1期75-78,共4页Chinese Journal of Experimental Surgery

基　　金：河南省科技攻关计划项目（132102310424）;河南省医学科技攻关计划项目（201403032）

摘　　要：目的探讨缺氧诱导因子-1α（HIF-1α）在布-加综合征（B-CS）大鼠模型肝组织的表达及与肝纤维化的关系。方法54只雄性Wistar大鼠按数字随机表法随机分为模型组、假手术组和正常组，分别在实验的第2、4、6周处死各组大鼠各6只，肝组织切片染色后观察病理变化。采用免疫组织化学法测定标本中HIF-1α、α-平滑肌肌动蛋白（α-SMA）、血管内皮生长因子（VEGF）、血小板源性生长因子（PDGF）水平，计算机图像分析测定肝组织纤维化面积比例。结果模型组肝组织出现肝细胞变性、坏死、纤维组织增生等纤维化改变，且随时间延长逐渐加重，假手术组和正常组肝组织无明显病理改变。第2、4、6周时，模型组HIF-1α（F＝288.400、369.540、964.230，均P＝0.000）、α-SMA（F＝145.520、334.060、671.710，均P＝0.000）、VEGF（F＝624.390、612.660、1 875.410，均P＝0.000）、PDGF（F＝84.950、467.880、671.340，均P＝0.000）和纤维化面积比例（F＝117.22、196.90、451.95，均P＝0.000）均显著高于假手术组和正常组，假手术组和正常组之间差异均无统计学意义。随时间延长，模型组HIF-1α、α-SMA、VEGF、PDGF和纤维化面积比例均显著增加（F＝133.020、74.970、139.250、78.660、84.490，均P＝0.000）。第2、4、6周时，模型组HIF-1α的表达与α-SMA（r＝0.865、0.822、0.878，P＝0.026、0.045、0.021）和纤维化面积比例（r＝0.860、0.835、0.823，P＝0.028、0.039、0.044）均呈正相关。结论B-CS大鼠模型肝组织存在HIF-1α表达量升高及纤维化改变，且HIF-1α与纤维化的进展具有明显相关性。Objective To explore the expression of hypoxia inducible factor-1α （HIF-1α） in Budd-Chiari syndrome （B-CS） model in rats and its correlation with hepatic fibrosis.Methods54 Wistar rats were randomly divided into 3 groups according to the method of random number table： model group, sham operation group, and normal group. Six rats from each group were sacrificed at the end of week 2, 4, and 6 for liver tissue collection. The pathological changes of liver tissues were evaluated by histological staining. The expression of HIF-1α, α-smooth muscle actin （α-SMA）, vascular endothelial growth factor （VEGF） and platelet derived growth factor （PDGF） was detected by immunohistochemistry, and the percentage of fibrosis area was determined by computer image analysis.ResultsLiver cell degeneration and necrosis, and fiber tissue hyperplasia were observed in model group, and the fibrosis was aggravated gradually as time prolonged. No pathological changes were found in sham operation group and normal group. At the end of week 2, 4 and 6, the expression of HIF-1α （F=288.400, 369.540, 964.230, all P=0.000）, α-SMA （F=145.520, 334.060, 671.710, all P=0.000）, VEGF （F=624.390, 612.660, 1875.410, all P=0.000）, PDGF （F=84.950, 467.880, 671.340, all P=0.000） and percentage of fibrosis area （F=117.220, 196.900, 451.950, all P=0.000） were significantly higher in model group than those in sham operation group and normal group, but there were no statistically significant differences between sham operation group and normal group. The expression of HIF-1α, α-SMA, VEGF and PDGF, and percentage of fibrosis area were increased significantly as time prolonged （F=133.020, 74.970, 139.250, 78.660, 84.490; all P=0.000）. At the end of week 2, 4 and 6, the expression of HIF-1α was positively associated with α-SMA （r=0.865, 0.822, 0.878; P=0.026, 0.045, 0.021） and fibrosis area （r=0.860, 0.835, 0.823; P=0.028, 0.039, 0.044）.ConclusionThere exist increased HIF-1α expression and hepatic fibro

关 键 词：布-加综合征 肝纤维化 缺氧诱导因子-1Α Α-平滑肌肌动蛋白 

分 类 号：R-332[医药卫生] R575