Expression of hypoxia-inducible factor-1 α in liver tissues of patients with chronic hepatitis B
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摘要:
目的研究肝组织中低氧诱导因子(HIF)-1α的表达与慢性乙型肝炎(CHB)患者肝脏微循环障碍的关系。方法对81例CHB患者和5例正常人的肝标本进行免疫组织化学染色,并用透射电镜观察肝组织超微结构的变化。结果 HIF-1α在肝组织中的表达强度和范围与CHB患者肝脏微循环障碍程度密切相关,电镜示肝窦腔内红细胞聚集、狄氏腔中胶原纤维沉积及肝窦内皮细胞表面有基底膜形成。结论 HIF-1α通过激活血管增生,最终导致血管纤维化和肝窦毛细血管化,加重肝脏微循环障碍。
Abstract:Objective To study the relationship between expression of hypoxia-inducible factor-1 alpha (HIF-1α) in liver tissue and disturbances in the liver microcirculatory system in patients with chronic hepatitis B (CHB) .Methods Liver biopsy samples were taken from 81 patients with CHB and five healthy controls.HIF-1α expression was detected in each sample by immunohistochemistry, and the ultrastructure of each sample was observed by transmission electron microscope (TEM) .Multiple comparisons were carried out by the Kruskal-Wallis rank test using a completely randomized design, and pairwise multiple comparisons were carried out by the Nemenyi test.Results Distribution of HIF-1α expression in different liver cell types was closely related to the degree of liver microcirculatory disturbance in patients with CHB.TEM showed that CHB liver samples had erythrocytes aggregated in the sinusoids, collagen fibers deposited in the Disse space, and a basal membrane formed on the surface of the sinusoidal endothelial cells.Conclusion HIF-1α may induce blood vessel fibrosis and sinusoidal capillarization in CHB liver by activating vascular proliferation, which could aggravate microcirculatory disturbances in the liver.
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Key words:
- cell hypoxia /
- hepatitis B /
- chronic
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[1]Semenza GL.HIF-1αand human disease:one highly in-volved factor[J].Genes Dev, 2000, 14 (16) :1983-1991. [2]Zou WL, Chen XG, Zang YJ, et al.Effect of prostaglandin E1on expression of hypoxia-inducible factor 1 alpha in rabbitswith portal hypertension[J].Med J The Chin People's ArmedPolice Forces, 2009, 20 (4) :310-312. (in Chinese) 邹卫龙, 陈新国, 臧运金, 等.缺氧诱导因子-1α在血吸虫家兔门静脉平滑肌细胞中的表达[J].武警医学, 2009, 20 (4) :310-312. [3]Chen YF.The correlation between apoptosis and HIF-1αex-pression in breast carcinoma[J].J Hainan Med Coll, 2009, 15 (10) :1205-1207. (in Chinese) 陈允峰.乳腺癌细胞凋亡与HIF-1α的相关性研究[J].海南医学院学报, 2009, 15 (10) :1205-1207. [4]Shammon AM, Bouchier-Hayes DJ, Condron CM, et al.Tumourhypoxia, chemotherapeutic resistance and hypoxia-related thera-pies[J].Cancer Treat Rev, 2003, 29 (4) :297-307. [5]Infection Disease and Parasitic Disease Institute and Liver Dis-ease Institute of Chinese Medical Association.Prevention andcure project to viral hepatitis[J].Chin J Hepatol, 2000, 8 (6) :324-329. (in Chinese) 中华医学会传染病与寄生虫病学分会、肝病学分会.病毒性肝炎防治方案[J].中华肝脏病杂志, 2000, 8 (6) :324-329. [6]LI YL.Pathology[M].Beijing:People's health publishingcompany, 2004:203. (in Chinese) 李玉林.病理学[M].北京:人民卫生出版社, 2004:203. [7] Semenza GL.A nuclear factor induced by hypoxia via De No-vo protein synthesis binds to the human erythropoietin geneenhancer at a site required for transcriptional activation[J].Mol Cell Boil, 1992, 12 (12) :5447-5451. [8]Liu LY, Yang LF, Cao Y.Latest advances in hypoxia induc-ible factor-1 signaling pathway[J].Int J Pathol Clin Med, 2011, 31 (3) :218-222. (in Chinese) 刘丽愉.低氧诱导因子信号通路的研究新进展[J].国际病理科学与临床杂志, 2011, 31 (3) :218-222. [9]Liu Y, Zhang C, Liu CH.Influence of hypoxia inducible factor-1αand p53 expression on liver injury after severe scald with de-layed fluid resuscitation in rats in high altitude[J].J LanzhouUniv (Med Sci) , 2011, 37 (1) :15-20. (in Chinese) 刘毅, 张诚, 刘长海.高海拔地区大鼠严重烫伤延迟复苏后肝脏低氧诱导因子-1α和P53的表达与肝脏损伤的关系[J].兰州大学学报 (医学版) , 2011, 37 (1) :15-20. [10]Lu YS, Gao ZL, Liu GY.Regulation of hypoxia-inducible factor1 on vascular endothelial growth factor[J].Chin J Gerontol, 2009, 29 (7) :905-907. (in Chinese) 陆蕴松, 高忠礼, 刘光耀.低氧诱导因子-1对血管内皮生长因子的调控[J].中国老年学杂志, 2009, 29 (7) :905-907. [11]Clerici C, Planes C.Gene regulation in the adaptive processto hypoxia in lung epithelial cells[J].Am J Physiol Lung CellMol Physiol, 2009, 296 (3) :1267-1274. [12]Chen ZY, Yan MX, Zhu D, et al.Effect of Ginkgo Biloba ex-tract on hypoxia-inducible factor 1αand vascular endothelialgrowth factor in rats with liver fibrosis[J].China J TraditChin Med Pharma, 2012, 27 (2) :488-491. (in Chinese) 陈芝芸, 严茂祥, 朱丹, 等.银杏叶提取物对肝纤维化大鼠肝脏低氧诱导因子1α及血管内皮生长因子表达的影响[J].中华中医药杂志, 2012, 27 (2) :488-491. [13]Blancher C, Harris AL.The molecular basis of the hypoxiaresponse pathway:tumour hypoxia as a therapy target[J].Cancer Metastasis Rev, 1998, 17 (2) :187-194. [14]Adms M, Kifazio LT, Rolandelli RH, et al.HIF-1:a key mediatorin hypoxia[J].Acta Physiol Hung, 2009, 96 (1) :19-28. [15]Yang L, Jiang YY.Research progress of hepatic sinusoidalendothelial cells and hepatic sinusoidal capillarization[J].In-fect Dis Informat, 2010, 23 (3) :183-186. (in Chinese) 杨丽, 江宇泳.肝窦内皮细胞与肝窦毛细血管化研究进展[J].传染病信息, 2010, 23 (3) :183-186.
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