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不同品系和性别的小鼠肾脏微血流动力学异质性评估

Evaluation of Renal Microhemodynamics Heterogeneity in Different Strains and Sexes of Mice.

作者信息

Xu Mengting, Fu Sunjing, Wang Bing, Song Xiaohong, Li Bingwei, Liu Xueting, Li Yuan, Wang Yingyu, Wang Qin, Ling Hao, Li Ailing, Liu Mingming, Zhang Xu

机构信息

Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China; International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing, China.

Department of Radiology, The Affiliated Changsha Central Hospital, Hengyang Medical School, University of South China, Changsha, China.

出版信息

Lab Invest. 2024 Jul;104(7):102087. doi: 10.1016/j.labinv.2024.102087. Epub 2024 May 24.

Abstract

Addressing the existing gaps in our understanding of sex- and strain-dependent disparities in renal microhemodynamics, this study conducted an investigation into the variations in renal function and related biological oscillators. Using the genetically diverse mouse models BALB/c, C57BL/6, and Kunming, which serve as established proxies for the study of renal pathophysiology, we implemented laser Doppler flowmetry conjoined with wavelet transform analyses to interrogate dynamic renal microcirculation. Creatinine, urea, uric acid, glucose, and cystatin C levels were quantified to investigate potential divergences attributable to sex and genetic lineage. Our findings reveal marked sexual dimorphism in metabolite concentrations, as well as strain-specific variances, particularly in creatinine and cystatin C levels. Through the combination of Mantel tests and Pearson correlation coefficients, we delineated the associations between renal functional metrics and microhemodynamics, uncovering interactions in female BALB/c mice for creatinine and uric acid, and in male C57BL/6 mice for cystatin C. Histopathologic examination confirmed an augmented microvascular density in female mice and elucidating variations in the expression of estrogen receptor β among the strains. These data collectively highlight the influence of both sex and genetic constitution on renal microcirculation, providing an understanding that may inform the etiologic exploration of renal ailments.

摘要

为了填补我们在理解肾脏微血流动力学中性别和品系依赖性差异方面的现有空白,本研究对肾功能和相关生物振荡器的变化进行了调查。利用基因多样化的小鼠模型BALB/c、C57BL/6和昆明小鼠(它们是研究肾脏病理生理学的既定替代模型),我们采用激光多普勒血流仪结合小波变换分析来研究动态肾脏微循环。对肌酐、尿素、尿酸、葡萄糖和胱抑素C水平进行定量,以研究性别和遗传谱系导致的潜在差异。我们的研究结果显示,代谢物浓度存在明显的性别二态性,以及品系特异性差异,特别是在肌酐和胱抑素C水平上。通过Mantel检验和Pearson相关系数的结合,我们描绘了肾功能指标与微血流动力学之间的关联,发现雌性BALB/c小鼠中肌酐和尿酸之间以及雄性C57BL/6小鼠中胱抑素C之间存在相互作用。组织病理学检查证实雌性小鼠的微血管密度增加,并阐明了各品系中雌激素受体β表达的变化。这些数据共同突出了性别和基因构成对肾脏微循环的影响,为肾脏疾病的病因探索提供了一种认识。

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