α3β1整合素在乙型肝炎病毒相关性肾炎肾组织的表达及与足细胞减少的关系

Expression ofα3β1 integrin in renal tissue of hepatitis B virus associated glomerulonephritis and its relation with podocyte reduction

目的探讨乙型肝炎病毒相关性肾炎(HBV-GN)患者肾组织肾小球足细胞数和α3β1整合素的变化在HBV-GN发病中的作用,并分析足细胞绝对数目及相对密度与临床指标的相关性。方法以2011至2018年22例HBV-GN患者的活检肾组织切片为HBV-GN组,30例肾脏肿瘤患者手术切除远离肿瘤的正常肾组织切片为对照组,用肾母细胞瘤抑制基因(WT1)单克隆抗体行免疫组化染色标记足细胞,采用人工计数和病理图像分析技术,估算单个肾小球足细胞绝对数目,测定单个肾小球中足细胞相对密度。用α3多克隆抗体和β1多克隆抗体对肾小球免疫组化染色,测定肾小球α3β1整合素的平均光密度值。结果HBV-GN组肾小球足细胞绝对数目及相对密度较对照组下降(P均<0.01),α3β1整合素表达水平较对照组下降(0.14±0.01 vs 0.05±0.01,P<0.01)。HBVGN患者足细胞绝对数目和相对密度分别与24 h尿蛋白呈负相关(r=-0.488,P=0.000;r=-0.470,P=0.000);与肾小球α3β1整合素表达水平分别呈正相关(r=0.314,P=0.023;r=0.299,P=0.031)。结论HBV-GN患者肾小球α3β1整合素表达下降可能引起足细胞黏附功能下降,致足细胞脱落,使肾小球足细胞数下降,造成患者蛋白尿,这些改变可能与HBV-GN的发病及进展有关。

Objective To explore the role of the changes of glomerular podocyte number andα3β1 integrin in the pathogenesis of hepatitis B virus associated glomerulonephritis(HBV-GN)and analyze the associations of absolute number and relative density of podocytes with clinical indexes.Methods Biopsy kidney tissue sections of 22 HBV-GN patients from 2011 to 2018 were selected as the HBV-GN group,normal kidney tissue sections removed from the renal tumor of 30 patients underwent surgical resection were as the control group.With Wilms'tumor suppressor gene(WT1)monoclonal antibody,immunohistochemical staining was performed to target podocytes.Podocyte number per glomerulus(Npodo)and podocyte numerical density(Nv)in a single glomerulus were determined by manual counting and pathological image analysis.The average optical density of glomerularα3β1 integrin was measured by immunohistochemical staining with polyclonal antibody againstα3β1.Results Compared with control group,Npodo,Nv andα3β1 integrin expression significantly decreased in HBV-GN group(all P<0.01).Npodo and Nv in HBV-GN group were negatively correlated with 24-h urinary protein,respectively(r=-0.488,P=0.000;r=-0.470,P=0.000)and were positively correlated withα3β1 integrin expression level(r=0.314,P=0.023;r=0.299,P=0.031).Conclusions Decreased expression of glomerularα3β1 integrin in HBV-GN patients may lead to the decrease of podocyte adhesion,podocyte abscission,the decrease of podocyte number and resulting in proteinuria in patients.These changes may be related to the pathogenesis and progress of HBV-GN.