目的:探讨狼疮性肾炎(lupus nephritis, LN)患者足细胞损伤与肾组织巨噬细胞浸润的关系,探索LN足细胞损伤的潜在机制。方法:选择初次诊治经肾活检组织病理学检查确诊为LN的患者60例作为病例组,其中肾疾病活动指数≥4分的38例纳入活动组,另选择10例因肾外伤行肾切除患者的正常肾组织作为对照组。通过光学显微镜和电子显微镜观察肾组织及足细胞的损伤,通过免疫组化、免疫荧光等方法检测60例LN患者及10例正常对照组患者的肾组织中足细胞特异性蛋白nephrin的表达和巨噬细胞(CD68 ⁺细胞)的浸润情况。多组间比较采用方差分析,组间两两比较采用LSD检验,两变量的相关性分析采用Pearson相关分析。 结果:(1)与正常对照组相比,LN患者nephrin表达显著减少,并且活动组LN患者肾nephrin的表达显著低于非活动组(P<0.05);(2)LN患者肾组织巨噬细胞明显多于正常对照组,主要分布在肾小球中,且活动组浸润的巨噬细胞数量多于非活动组(P<0.05);(3) LN患者肾组织中nephrin的表达与巨噬细胞的浸润呈负相关(r=0.761, P<0.001)。结论:LN肾组织中巨噬细胞浸润可能是狼疮肾炎足细胞损伤的重要机制之一。

Objective: To investigate the relationship between the expression of nephrin and the infiltration of macrophages in renal tissues in patients with lupus nephritis (LN), and to provide the evidence of potential mechanism of podocyte injury in LN.Methods: In the study, 60 patients who were first diagnosed with LN by pathology were selected including 38 active LN patients with r-SLEDAI≥4, and another 10 patients of normal renal tissue were excised as a normal control group. The renal tissue and podocyte injury were observed through light and transmission electron microscope. The expression of nephrin and the infiltration of macrophages (CD68 ⁺cells) in the renal tissue of the 60 LN patients and 10 normal cases were detected by immunohistochemical and immunofluorescence method. Different statistical analysis methods were used to analyze the correlation between the variables. Variance analysis was used for comparison among the groups, while LSD test was used for comparison between every two groups. Pearson correlation analysis was used to analyze the correlation between the variables.Results: (1)Of all the LN patients, 24 h urinary protein [(3.94±1.76) vs. (1.56±0.68), P<0.05], erythrocyte sedimentation rate (ESR) [(79.83±6.3) vs. (40.1±10.5), P<0.05] and serum creatinine [(106.58±14.9) vs. (79.1±9.89), P<0.05] were significantly increased in active group than those in inactive group, while C3 [(0.34±0.12) vs. (0.78±0.11), P<0.05], C4 [(0.07±0.04) vs. (0.17±0.10), P<0.05] and eGFR [(62.42±5.16) vs. (81.33±4.53), P<0.05] were significantly decreased in active group. (2)Compared with the normal control group, the expression of nephrin in renal tissue of the LN patients was significantly decreased, and the expression of nephrin in the active patients was significantly lower than that in inactive group (P<0.05). (3)Compared with the normal control group, the number of infiltrated macrophages in the LN patients was significantly increased, especially in the active patients (P<0.05). Macrophages were mainly found in glomeruli. (4)There was a significant negative correlation between the expression of nephrin and macrophage infiltration in renal tissues of the LN patients (r=0.761, P<0.001).Conclusion: Macrophage infiltration in renal tissues may be one of the potential mechanisms of podocyte injury in lupus nephritis.