Yin Lei, Tian Fei, Li Zhengyong, Chen Wenqing, Liu Chang, Zhang Yilin, Liu Dongwei, Liu Zhangsuo
Department of Prevention and Health Care, Military Hospital of Henan Province, Zhengzhou, Henan Province, China.
Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, China.
J Transl Int Med. 2025 May 9;13(2):118-127. doi: 10.1515/jtim-2025-0022. eCollection 2025 Apr.
The incidence of idiopathic membranous nephropathy (IMN) has been increasing in recent years and is closely correlated with fine particulate matter particulate matter (PM) 2.5. Thus, the relationship between polycyclic aromatic hydrocarbons (PAHs), one of the main components of PM2.5, and IMN should be explored.
Patients with IMN and healthy control (HC) individuals were screened, and the concentrations and clinical indicators of blood PAHs were detected in these two groups for statistical analysis. Immortalized mouse podocyte cells were treated with 6.25, 12.5, and 25 μg/mL Benzo[b]fluoranthene (BbF) for 72 h. The cell morphology was observed, and the expressions of nephrin and synaptopodin (Synpo) were detected. On days 0 and 2, 1.25 mg/kg BbF was intratracheally administered to the rats. The rats were sacrificed on day 0, day 3, day 7, and day 14. The glomerulus was observed under a microscope, and the nephrin expression was detected.
Compared with the HC group, the total concentration of PAHs in the IMN group was significantly increased ( < 0.001), and the between-group diference was -3.031 μg/mL (95% confidence interval, -3.739 to -2.324). The total concentration of PAHs in the IMN group was significantly negatively correlated with total protein (TP) and albumin (ALB) and significantly positively correlated with β2 microglobulin (β2-MG) and 24-hour urine TP (24hTP). Among them, BbF was not only negatively correlated with TP and ALB but also positively correlated with cystatin C, β2-MG, and 24hTP and was positively correlated with anti-phospholipase A2 receptor ( < 0.05). In cell experiments, the cell morphology became irregular, the cytoplasm started to shrink, the number of cells decreased with increasing BbF concentration, and the expressions of nephrin and Synpo decreased with increasing BbF concentration. In animal experiments, glomeruli had marked inflammatory cell infiltration in hematoxylin and eosin staining, mesangial cell proliferation and increased mesangial matrix in periodic acid-Schif staining, and deposition of a small number of immune complexes in Masson staining over time, and the nephrin expression gradually decreased.
This study showed that the total concentration of PAHs in the blood of patients with IMN significantly increased, and BbF is significantly correlated with the disease severity of IMN, suggesting that PAHs are correlated with IMN occurrence and development and may play a certain role in IMN.
近年来，特发性膜性肾病（IMN）的发病率呈上升趋势，且与细颗粒物（PM）2.5密切相关。因此，应探讨PM2.5的主要成分之一多环芳烃（PAHs）与IMN之间的关系。
筛选IMN患者和健康对照（HC）个体，检测两组血液中PAHs的浓度及临床指标并进行统计分析。用6.25、12.5和25μg/mL的苯并[b]荧蒽（BbF）处理永生化小鼠足细胞72小时。观察细胞形态，检测nephrin和突触足蛋白（Synpo）的表达。在第0天和第2天，对大鼠气管内注射1.25mg/kg BbF。在第0天、第3天、第7天和第14天处死大鼠。在显微镜下观察肾小球，并检测nephrin的表达。
与HC组相比，IMN组PAHs的总浓度显著升高（<0.001），组间差异为-3.031μg/mL（95%置信区间，-3.739至-2.324）。IMN组PAHs的总浓度与总蛋白（TP）和白蛋白（ALB）显著负相关，与β2微球蛋白（β2-MG）和24小时尿TP（24hTP）显著正相关。其中，BbF不仅与TP和ALB呈负相关，还与胱抑素C、β2-MG和24hTP呈正相关，且与抗磷脂酶A2受体呈正相关（<0.05）。在细胞实验中，随着BbF浓度增加，细胞形态变得不规则，细胞质开始收缩，细胞数量减少，nephrin和Synpo的表达降低。在动物实验中，苏木精-伊红染色显示肾小球有明显的炎性细胞浸润，高碘酸-希夫染色显示系膜细胞增殖和系膜基质增加，随着时间推移，Masson染色显示有少量免疫复合物沉积，nephrin表达逐渐降低。
本研究表明，IMN患者血液中PAHs的总浓度显著升高，且BbF与IMN的疾病严重程度显著相关，提示PAHs与IMN的发生发展相关，可能在IMN中起一定作用。
