摘要
目的探讨低氧诱导因子-1α(HIF-1α)在大鼠肝肺综合征(HPS)发病中的作用及其与糖调节蛋白78(GRP78)的关系。方法复合致病因素法制备HPS大鼠模型。Western blotting法检测肺组织HIF-1α、血管内皮生长因子164(VEGF164)及GRP78蛋白表达水平。免疫组化染色法观察肺组织VEGF受体2(VEGFR-2)及CD105的表达。结果模型组动物肺组织HIF-1α蛋白表达水平在第8周显著高于同期正常对照组及4周、6周组;GRP78蛋白表达随病程进展逐渐升高,至第8周达到最高水平,各时间点之间以及与同期正常对照组比较差异均具有统计学意义;VEGF164蛋白表达随病程进展逐渐增加,至6周达到高峰,各时间点均显著高于同期正常对照组,6周和8周表达水平显著高于4周;VEGFR-2及CD105免疫组化染色强度和数量均随HPS进展逐渐增高;GRP78分别与VEGF164、VEGFR-2及CD105的表达水平呈正相关(P<0.05),HIF-1α与GRP78亦呈正相关关系(P<0.05)。结论 HIF-1α可能在HPS发病中起一定作用,与GRP78共同促进了肺微血管重构。
ABSTRACT：Objective To explore the role of HIF‐1αin the pathogenesis of hepatopulmonary syndrome （HPS） and its relationship with GRP78 .Methods The HPS model in rats was induced by multiple pathogenic factor .The samples were assessed by using Western blotting analysis for HIF‐lα, GRP78 and VEGF164 . The expressions of VEGFR‐2 and CD105 were observed by using immunohistochemical staining .Results The protein level of HIF‐1αwas significantly increased in HPS group at week 8 compared with that at week 4 and 6 groups and corresponding normal control groups .With the development of HPS ,protein level of GRP78 was gradually increased at each time point significantly and reached the highest level at week 8 ;protein level of VEGF164 showed a similar change with GRP78 ,but the peak was at week 6 .Immunohistochemical results showed that the protein expressions of VEGFR‐2 and CD105 were gradually increased in lung tissue as HPS progressed .The protein level of GRP78 was positively correlated with HIF‐1α,VEGF164 ,VEGFR‐2 and CD105 ,respectively （P〈0 .05） .Conclusion HIF‐1αis most likely together with GRP78 to play a critical role in promoting pulmonary microvascular remodeling in the pathogenesis of HPS in rats .
出处
《西安交通大学学报（医学版）》
CAS
CSCD
北大核心
2016年第4期513-517,524,共6页
Journal of Xi’an Jiaotong University（Medical Sciences）
基金
国家自然科学基金资助项目(No.81070339)
山西省国际科技合作计划项目(No.2010081068)
山西省回国留学人员科研资助项目(No.211-091)
山西医科大学细胞生理学省部共建教育部重点实验室主任基金资助项目(No.2010-09)~~
