基于血管生成信号探讨孕前PM_(2.5)暴露对子代成年小鼠心脏功能的影响  

Effects of preconception PM_(2.5) exposure on the cardiac function of offspring adult mice based on angiogenic signaling

作　　者：张英英 孙谊然 白文琳[1] 孙文 雷立健[1] ZHANG Ying-ying;SUN Yi-ran;BAI Wen-lin;SUN Wen;LEI Li-jian(School of Public Health,Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学公共卫生学院,太原030001

出　　处：《环境卫生学杂志》2023年第12期882-889,共8页JOURNAL OF ENVIRONMENTAL HYGIENE

基　　金：国家自然科学基金青年项目(82103938);山西省高等学校科技创新项目(2020L0176);山西医科大学校级博士启动基金项目(XD1916);山西省基础研究计划青年项目(20210302124038)。

摘　　要：目的探讨孕前细颗粒物(PM_(2.5))暴露对子代成年小鼠心脏功能的影响及其作用机制。方法28只8周龄雌性C57BL/6J小鼠随机分为对照组和PM_(2.5)暴露组,每组14只。暴露组小鼠采用3 mg/kg的PM_(2.5)混悬液进行鼻腔滴注,对照组采用经空白采样膜处理的悬液进行滴注,隔天1次,持续4周。染毒结束后将各组雌鼠与正常雄鼠按雌雄2∶1的比例合笼过夜,次日早晨观察到阴栓则确定为妊娠。对两组雌鼠的子代小鼠进行体重监测并持续喂养至第10周,6只进行心功能检测,3只进行心脏组织的病理学切片,4只进行生物学机制探讨,检测缺氧诱导因子-1α(HIF-1α)/血管内皮生长因子(VEGF)信号通路以及血管生成分子标志物,包括血小板内皮细胞粘附分子(CD31)、血管生成素1(Ang1)和血管性血友病因子(vWF)的mRNA表达水平。结果与对照组相比,孕前PM_(2.5)暴露对子代小鼠(出生后第7天)的体重增加有显著抑制作用;成年后小鼠表现出左心室质量(LVM)、左心室舒张末期前壁厚度(LVAW-d)和左心室舒张末期后壁厚度(LVPW-d)显著增大的结构水平变化,心脏收缩功能参数左心室射血分数(EF)、左心室短轴缩短率(FS)和每搏输出量(SV)显著降低、心脏舒张功能参数等容收缩时间(IVRT)升高以及心脏功能综合参数心肌功能指数(Tei)显著升高的功能水平变化,同时伴有心脏增大、炎性细胞浸润、血管异常等病理水平变化。进一步分子生物学检测结果表明孕前PM_(2.5)暴露对子代成年小鼠血管生成过程产生影响。结论孕前PM_(2.5)暴露可能通过HIF-1α/VEGF信号干扰血管生成过程,进而引起成年子代心脏功能的改变。Objective To investigate the effects of preconception exposure to fine particulate matter(PM_(2.5))on the cardiac function of offspring adult mice and its underlying mechanism.Methods Twenty-eight 8-week-old female C57BL/6J mice were randomly divided into control group and PM_(2.5) exposure group,with 14 mice per group.The exposure group received intranasal infusion of a PM_(2.5) suspension at 3 mg/kg,while the control group received a suspension treated with a blank sampling membrane,once every two days for four weeks.At the end of the exposure,the female mice in each group were caged with normal male mice overnight at a ratio of 2∶1,and the presence of vaginal plugs on the next morning indicated the occurrence of pregnancy.The offspring of the two groups were fed and monitored for body weight until the 10th week.Six mice were examined for cardiac function,3 mice were examined for pathological changes on heart slices,and 4 mice were examined for the mRNA expression levels of the hypoxia-inducible factor-1α(HIF-1α)/vascular endothelial growth factor(VEGF)signaling pathway and angiogenesis markers,including platelet-endothelial cell adhesion molecule(CD31),angiopoietin-1,and von Willebrand factor(vWF).Results Compared with the control group,preconception PM_(2.5) exposure had a significant inhibitory effect on the body weight of offspring mice(post-natal day 7).Offspring adult of the exposure group showed significantly increased left ventricular mass(LVM),left ventricular end-diastolic anterior wall thickness(LVAW-d),and left ventricular end-diastolic posterior wall thickness(LVPW-d);significantly decreased systolic parameters of left ventricular ejection fraction(EF),left ventricular fractional shortening(FS),and stroke volume(SV);significantly increased diastolic parameter(isovolumic contraction time,IVRT)and myocardial function parameter(Tei);and pathological changes including heart enlargement,inflammatory cell infiltration,and vascular abnormalities.Further molecular analysis showed that preconception PM_

关 键 词：孕前 细颗粒物(PM_(2.5)) 心脏功能 血管生成 

分 类 号：R114[医药卫生—卫生毒理学]