Wang Bing, Li Yuan, Ouyang Qin, Xu Meng-Ting, Wang Ying-Yu, Fu Sun-Jing, Liu Wei-Qi, Liu Xue-Ting, Ling Hao, Zhang Xu, Xiu Rui-Juan, Liu Ming-Ming
Institute of Microcirculation, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100005, China.
International Center of Microvascular Medicine, Chinese Academy of Medical Sciences, Beijing 100005, China.
World J Gastroenterol. 2025 Apr 21;31(15):101058. doi: 10.3748/wjg.v31.i15.101058.
The integrity and functionality of the hepatic microcirculation are essential for maintaining liver health, which is influenced by sex and genetic background. Understanding these variations is crucial for addressing disparities in liver disease outcomes.
To investigate the sexual dimorphism and genetic heterogeneity of liver microcirculatory function in mice.
We assessed hepatic microhemodynamics in BALB/c, C57BL/6J, and KM mouse strains using laser Doppler flowmetry and wavelet analysis. We analyzed the serum levels of alanine transaminase, glutamic acid aminotransferase, total bile acid, total protein, alkaline phosphatase, and glucose. Histological and immunohistochemical staining were employed to quantify microvascular density and the expression levels of cluster of differentiation (CD) 31, and estrogen receptor α, and β. Statistical analyses, including the Mantel test and Pearson correlation, were conducted to determine the relationships among hepatic function, microcirculation, and marcocirculation between different sexes and across genetic backgrounds.
We identified sex-based disparities in hepatic microhemodynamics across all strains, with males exhibiting higher microvascular perfusion and erythrocyte concentration, but lower blood velocity. Strain-specific differences were evident, particularly in the endothelial oscillatory characteristics of the erythrocyte concentration. No sex-dependent differences in estrogen receptor expression were observed, while significant variations in CD31 expression and microvascular density were observed. The correlations highlighted relationships between hepatic microhemodynamics and liver function indicators.
Our findings indicate the influence of genetic and sex differences on hepatic microcirculation and liver function, highlighting the necessity of incorporating both genetic background and sex into hepatic physiology studies and potential liver disease management strategies.
肝微循环的完整性和功能对于维持肝脏健康至关重要，而其受到性别和遗传背景的影响。了解这些差异对于解决肝病结局的差异至关重要。
研究小鼠肝脏微循环功能的性别二态性和遗传异质性。
我们使用激光多普勒血流仪和小波分析评估了BALB/c、C57BL/6J和KM小鼠品系的肝脏微血流动力学。我们分析了血清丙氨酸转氨酶、谷氨酸转氨酶、总胆汁酸、总蛋白、碱性磷酸酶和葡萄糖水平。采用组织学和免疫组织化学染色来量化微血管密度以及分化簇（CD）31、雌激素受体α和β的表达水平。进行了包括Mantel检验和Pearson相关性分析在内的统计分析，以确定不同性别和不同遗传背景之间肝功能、微循环和大循环之间的关系。
我们在所有品系中均发现了基于性别的肝脏微血流动力学差异，雄性表现出更高的微血管灌注和红细胞浓度，但血流速度较低。品系特异性差异明显，尤其是在红细胞浓度的内皮振荡特征方面。未观察到雌激素受体表达的性别依赖性差异，而观察到CD31表达和微血管密度存在显著差异。相关性分析突出了肝脏微血流动力学与肝功能指标之间的关系。
我们的研究结果表明遗传和性别差异对肝脏微循环和肝功能有影响，强调了将遗传背景和性别纳入肝脏生理学研究以及潜在肝病管理策略的必要性。
