Department of Pharmacology and Toxicology, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.
Biology Department, Faculty of Sciences-I, Lebanese University, Beirut, Lebanon.
Physiol Rep. 2020 Jan;8(2):e14339. doi: 10.14814/phy2.14339.
Multiple clinical studies documented renal damage in chronic cigarette smokers (CS) irrespective of their age and gender. Premenopausal female smokers are known to exert a certain cardiovascular and renal protection with undefined mechanisms. Given the multiple demographic variables within clinical studies, this experimental study was designed to be the first to assess whether gender-biased CS-induced kidney damage truly exists between premenopausal female and age-matched C57Bl6J male mice when compared to their relative control groups. Following 6 weeks of CS exposure, cardiac function, inflammatory marker production, fibrosis formation, total and glomerular ROS levels, and glomerulotubular homeostasis were assessed in both genders. Although both CS-exposed male and female mice exhibited comparable ROS fold change relative to their respective control groups, CS-exposed male mice showed a more pronounced fibrotic deposition, inflammation, and glomerulotubular damage profile. However, the protection observed in CS-exposed female group was not absolute. CS-exposed female mice exhibited a significant increase in fibrosis, ROS production, and glomerulotubular alteration but with a pronounced anti-inflammatory profile when compared to their relative control groups. Although both CS-exposed genders presented with altered glomerulotubular homeostasis, the alteration phenotype between genders was different. CS-exposed males showed a significant decrease in Bowman's space along with reduced tubular diameter consistent with an endocrinization pattern of chronic tubular atrophy, suggestive of an advanced stage of glomerulotubular damage. CS-exposed female group, on the other hand, displayed glomerular hypertrophy with a mild tubular dilatation profile suggestive of an early stage of glomerulotubular damage that generally precedes collapse. In conclusion, both genders are prone to CS-induced kidney damage with pronounced female protection due to a milder damage slope.
多项临床研究记录了慢性吸烟（CS）者的肾脏损害，无论其年龄和性别如何。已知绝经前女性吸烟者具有未定义的机制发挥一定的心血管和肾脏保护作用。鉴于临床研究中的多个人口统计学变量，这项实验研究旨在首次评估与年龄匹配的 C57Bl6J 雄性小鼠的相对对照组相比，绝经前女性和 CS 诱导的肾脏损伤是否确实存在性别偏见。在 CS 暴露 6 周后，评估了两性的心脏功能、炎症标志物产生、纤维化形成、总和肾小球 ROS 水平以及肾小球肾小管稳态。尽管 CS 暴露的雄性和雌性小鼠的 ROS 折叠变化与各自的对照组相比相当，但 CS 暴露的雄性小鼠显示出更明显的纤维化沉积、炎症和肾小球肾小管损伤特征。然而，在 CS 暴露的雌性组中观察到的保护并非绝对的。与相对对照组相比，CS 暴露的雌性小鼠表现出明显的纤维化、ROS 产生和肾小球肾小管改变，但具有明显的抗炎特征。尽管暴露于 CS 的两种性别都表现出肾小球肾小管稳态的改变，但性别之间的改变表型不同。CS 暴露的雄性表现出明显的 Bowman 空间减少以及管状直径减小，与慢性肾小管萎缩的内分泌化模式一致，提示肾小球肾小管损伤的晚期。另一方面，CS 暴露的雌性组显示出肾小球肥大和轻微的管状扩张特征，提示肾小球肾小管损伤的早期阶段，通常先于塌陷。总之，两性都容易受到 CS 诱导的肾脏损伤的影响，由于损伤斜率较轻，女性保护作用明显。
