AQP1、AQP4表达与乙肝肝纤维化进展的相关性研究

Correlation of expressions of AQP1 and AQP4 with progress of hepatitis B liver fibrosis

目的探讨慢性乙肝患者水通道蛋白1(AQP1)、水通道蛋白4(AQP4)在肝组织中的表达与肝纤维化程度之间的相关性及意义。方法选取61例在我院行肝脏穿刺活检的慢性乙肝患者的活检样本,对样本进行HE染色,应用Scheuer系统评估所有患者的纤维化分期和炎症分级。免疫组化法测定肝组织中AQP1、AQP4的表达及定位情况。培养人的肝星状细胞(hepatic stellate cell,HSC),采用细胞免疫组化方法进行AQP1、AQP4免疫组化染色。对肝组织免疫组化切片进行平均光密度值(IOD)半定量分析,采用Kruskal-Wallis秩和检验对不同肝纤维化分期及炎症分级的IOD值进行显著性差异分析,采用Kendall检验进行相关性分析。结果在肝纤维化S0期,AQP1主要表达在动脉、门脉血管的内皮细胞和胆管上皮细胞,随着纤维化进展,AQP1大量表达在增殖的动脉毛细血管内皮细胞、胆管上皮细胞,并随着纤维化进展表达量增加;AQP4在胆管上皮细胞和HSC表达,随着肝纤维化进展和HSC活化,其表达增加。在细胞水平发现,AQP4在HSC明显表达。AQP1和AQP4的表达随肝纤维化分期及炎症分级进展而逐渐增加,与肝纤维化分期及炎症分级呈正相关(P<0.05)。结论AQP1、AQP4与乙肝肝纤维化的进展关系密切,AQP1可能与肝纤维化病理性动脉毛细血管生成有关,而AQP4可能参与HSC的活化从而参与乙肝肝纤维化过程中细胞外基质(extracellular matrix,ECM)的生成。

Objective To investigate the correlation and significance of the expressions of AQP1,AQP4 with the degree of liver fibrosis in patients with HBV.Methods Sixty-one patients with chronic HBV infection who underwent liver biopsy in our hospital were selected.The biopsy samples were performed hematoxylin-eosin(HE)stain to evaluate the fibrosis stage and inflammation grade according to Scheuer system.The expressions and localizations of AQP1,AQP4 in liver tissue were detected by immunohistochemistry.The human hepatic stellate cells(HSC)were cultured and immunohistochemical stain with AQP1,AQP4 were performed.The average optical density(IOD)of liver tissue immunohistochemical sections was semi-quantitatively analyzed,then the significant difference and correlation of IOD values in different stages of liver fibrosis and inflammatory grades were analyzed.Kruskal-Wallis rank sum test was used for significant difference analysis and Kendall test was used for correlation analysis.Results In liver fibrosis stage of S0,AQP1 mainly expressed in the endothelial cells of arteries and portal vessels and bile duct epithelial cells,with the progress of fibrosis,AQP1 abundantly expressed in proliferating capillary endothelial cells and bile duct epithelial cells,increased with the progression of fibrosis;AQP4 expressed not only in bile duct epithelial cells but also in HSC,the expression of AQP4 was increased with the activation of HSC.At the cellular level,AQP4 had a strong expression in HSC.The expressions of AQP1 and AQP4 were increased with the progression of liver fibrosis stage and inflammation grade and positively correlated with both of them(P<0.05).Conclusion AQP1,AQP4 are closely related to the progress of liver fibrosis.AQP1 may be related to the formation of pathological arterial capillaries,AQP4 may participate in the activation of HSC and the formation of extracellular matrix(ECM)in the process of HBV liver fibrosis.