Wang Hao, Ma Li, Guo Yuqiong, Ren Lingyu, Li Guangke, Sang Nan
Shanxi Key Laboratory of Coal-Based Emerging Pollutant Identification and Risk Control, Research Center of Environment and Health, College of Environment and Resource, Shanxi University, Taiyuan 030006, China.
Toxics. 2024 Dec 1;12(12):878. doi: 10.3390/toxics12120878.
As one of the most common air pollutants, fine particulate matter (PM) increases the risk of diseases in various systems, including the urinary system. In the present study, we exposed male and female C57BL/6J mice to PM for 8 weeks. Examination of renal function indices, including creatinine (CRE), blood urea nitrogen (BUN), uric acid (UA), and urinary microalbumin, indicated that the kidneys of female mice, not male mice, underwent early renal injury, exhibiting glomerular hyperfiltration. Meanwhile, pathological staining showed that the kidneys of female mice exhibited enlarged glomerulus that filled the entire Bowman's capsule in the female mice. Afterward, we explored the potential causes and mechanisms of glomerular hyperfiltration. Variations in mRNA levels of key genes involved in the renin-angiotensin system (RAS) and kallikrein-kinin system (KKS) demonstrated that PM led to elevated glomerular capillary hydrostatic pressure in female mice by disturbing the balance between the RAS and KKS, which in turn increased the glomerular filtration rate (GFR). In addition, we found that PM increased blood glucose levels in the females, which enhanced tubular reabsorption of glucose, attenuated macular dense sensory signaling, induced renal hypoxia, and affected adenosine triphosphate (ATP) synthesis, thus attenuating tubuloglomerular feedback (TGF)-induced afferent arteriolar constriction and leading to glomerular hyperfiltration. In conclusion, this study indicated that PM induced glomerular hyperfiltration in female mice by affecting RAS/KKS imbalances, as well as the regulation of TGF; innovatively unveiled the association between PM subchronic exposure and early kidney injury and its gender dependence; enriched the toxicological evidence of PM and confirmed the importance of reducing ambient PM concentrations.
作为最常见的空气污染物之一，细颗粒物（PM）会增加包括泌尿系统在内的各种系统疾病的风险。在本研究中，我们将雄性和雌性C57BL/6J小鼠暴露于PM中8周。对包括肌酐（CRE）、血尿素氮（BUN）、尿酸（UA）和尿微量白蛋白在内的肾功能指标进行检测，结果表明，雌性小鼠而非雄性小鼠的肾脏出现了早期肾损伤，表现为肾小球高滤过。同时，病理染色显示雌性小鼠的肾脏肾小球增大，充满了雌性小鼠的整个鲍曼囊。随后，我们探讨了肾小球高滤过的潜在原因和机制。肾素-血管紧张素系统（RAS）和激肽释放酶-激肽系统（KKS）中关键基因的mRNA水平变化表明，PM通过扰乱RAS和KKS之间的平衡，导致雌性小鼠肾小球毛细血管静水压升高，进而增加肾小球滤过率（GFR）。此外，我们发现PM使雌性小鼠血糖水平升高，这增强了肾小管对葡萄糖的重吸收，减弱了致密斑感觉信号，诱导肾缺氧并影响三磷酸腺苷（ATP）合成，从而减弱了管球反馈（TGF）诱导的入球小动脉收缩，导致肾小球高滤过。总之，本研究表明PM通过影响RAS/KKS失衡以及TGF的调节诱导雌性小鼠肾小球高滤过；创新性地揭示了PM亚慢性暴露与早期肾损伤及其性别依赖性之间的关联；丰富了PM的毒理学证据，并证实了降低环境PM浓度的重要性。
