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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。
Objective To investigate the role of hypoxia inducible factor-1α (HIF-1α) in the pathogenesis of hepatopulmonary syndrome (HPS) in rats and its relationship with carbohydrate regulatory protein 78 (GRP78). Methods The compound pathogenic factors were used to prepare HPS rat model. The expression of HIF-1α, VEGF164 and GRP78 protein in lung tissue were detected by Western blotting. Immunohistochemical staining was used to observe the expression of VEGFR-2 and CD105 in lung tissue. Results The expression of HIF-1α protein in lung tissue of model group was significantly higher than that of the normal control group and the 4th and 6th weeks in the 8th week. The expression of GRP78 protein gradually increased with the progression of the disease and reached the highest level in the 8th week. VEGF164 protein expression gradually increased with the progress of the disease, reaching the peak at 6 weeks, at each time point were significantly higher than the normal control group at the same period, 6 weeks and 8 weeks The expression of VEGFR-2 and CD105 increased with the progression of HPS. The expression of GRP78 was positively correlated with the expression of VEGF164, VEGFR-2 and CD105 (P <0.05), while the expression of HIF- 1α and GRP78 also showed a positive correlation (P <0.05). Conclusion HIF-1α may play a role in the pathogenesis of HPS, and together with GRP78, promote pulmonary microvascular remodeling.