Background:Intestinal microcirculation is a critical interface for nutrient exchange and energy transfer,and is essential for maintaining physiological integrity.Our study aimed to elucidate the relationships among in...Background:Intestinal microcirculation is a critical interface for nutrient exchange and energy transfer,and is essential for maintaining physiological integrity.Our study aimed to elucidate the relationships among intestinal microhemodynamics,genetic background,sex,and microbial composition.Methods:To dissect the microhemodynamic landscape of the BALB/c,C57BL/6J,and KM mouse strains,laser Doppler flowmetry paired with wavelet transform analysis was utilized to determine the amplitude of characteristic oscillatory patterns.Microbial consortia were profiled using 16S rRNA gene sequencing.To augment our investigation,a broad-spectrum antibiotic regimen was administered to these strains to evaluate the impact of gut microbiota depletion on intestinal microhemodynamics.Immunohistochemical analyses were used to quantify platelet endothelial cell adhesion molecule-1(PECAM-1),estrogen receptorα(ESR1),and estrogen receptorβ(ESR2)expression.Results:Our findings revealed strain-dependent and sex-related disparities in microhemodynamic profiles and characteristic oscillatory behaviors.Significant differences in the gut microbiota contingent upon sex and genetic lineage were observed,with correlational analy-ses indicating an influence of the microbiota on microhemodynamic parameters.Following antibiotic treatment,distinct changes in blood perfusion levels and velocities were observed,including a reduction in female C57BL/6J mice and a general decrease in perfusion velocity.Enhanced erythrocyte aggregation and modulated endothelial function post-antibiotic treatment indicated that a systemic response to microbiota depletion impacted cardiac amplitude.Immunohistochemical data revealed strain-specific and sex-specific PECAM-1 and ESR1 expression patterns that aligned with observed intestinal microhemodynamic changes.Conclusions:This study highlights the influence of both genetic and sex-specific factors on intestinal microhemodynamics and the gut microbiota in mice.These findings also emphasize a substantial correlation between intestinal microhemodynamics and the compositional dynamics of the gut bacterial community.展开更多
BACKGROUND 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 add...BACKGROUND 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.AIM To investigate the sexual dimorphism and genetic heterogeneity of liver microcirculatory function in mice.METHODS 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 receptorα,andβ.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.RESULTS 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 sexdependent 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.CONCLUSION 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.展开更多
基金supported by the CAMS Innovation Fund for Medical Sciences[2022-I2M-1-026]the Beijing Municipal Natural Science Foundation[No.7212068]the National Natural Science Foundation of China[No.81900747].
文摘Background:Intestinal microcirculation is a critical interface for nutrient exchange and energy transfer,and is essential for maintaining physiological integrity.Our study aimed to elucidate the relationships among intestinal microhemodynamics,genetic background,sex,and microbial composition.Methods:To dissect the microhemodynamic landscape of the BALB/c,C57BL/6J,and KM mouse strains,laser Doppler flowmetry paired with wavelet transform analysis was utilized to determine the amplitude of characteristic oscillatory patterns.Microbial consortia were profiled using 16S rRNA gene sequencing.To augment our investigation,a broad-spectrum antibiotic regimen was administered to these strains to evaluate the impact of gut microbiota depletion on intestinal microhemodynamics.Immunohistochemical analyses were used to quantify platelet endothelial cell adhesion molecule-1(PECAM-1),estrogen receptorα(ESR1),and estrogen receptorβ(ESR2)expression.Results:Our findings revealed strain-dependent and sex-related disparities in microhemodynamic profiles and characteristic oscillatory behaviors.Significant differences in the gut microbiota contingent upon sex and genetic lineage were observed,with correlational analy-ses indicating an influence of the microbiota on microhemodynamic parameters.Following antibiotic treatment,distinct changes in blood perfusion levels and velocities were observed,including a reduction in female C57BL/6J mice and a general decrease in perfusion velocity.Enhanced erythrocyte aggregation and modulated endothelial function post-antibiotic treatment indicated that a systemic response to microbiota depletion impacted cardiac amplitude.Immunohistochemical data revealed strain-specific and sex-specific PECAM-1 and ESR1 expression patterns that aligned with observed intestinal microhemodynamic changes.Conclusions:This study highlights the influence of both genetic and sex-specific factors on intestinal microhemodynamics and the gut microbiota in mice.These findings also emphasize a substantial correlation between intestinal microhemodynamics and the compositional dynamics of the gut bacterial community.
基金Supported by the Beijing Municipal Natural Science Foundation,No.7212068the National Natural Science Foundation of China,No.81900747.
文摘BACKGROUND 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.AIM To investigate the sexual dimorphism and genetic heterogeneity of liver microcirculatory function in mice.METHODS 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 receptorα,andβ.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.RESULTS 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 sexdependent 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.CONCLUSION 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.
