母亲孕期高脂饮食促进子代主动脉血管内皮间充质转变  

Maternal high-fat diet during pregnancy promotes aortic endothelial to mesenchymal transition in offspring

作　　者：何慧 朱沅 董豆豆 丁萌 姜天宇 莫晓川 王筑婷 欧海龙 HE Hui;ZHU Yuan;DONG Doudou;DING Meng;JIANG Tianyu;MO Xiaochuan;WANG Zhuting;OU Hailong(Department of Biochemistry and Molecular Biology,School of Basic Medicine,Guizhou Medical University,Guiyang,Guizhou 561113,China)

机构地区：[1]贵州医科大学基础医学院生物化学与分子生物学教研室,贵州省贵阳市561113

出　　处：《中国动脉硬化杂志》2024年第11期939-946,共8页Chinese Journal of Arteriosclerosis

基　　金：国家自然科学基金(32260232和32060219);贵州省科技基金(黔科合基础-ZK[2022]重点038)。

摘　　要：[目的]研究小鼠在孕期给予高脂饲料喂养对其成年子代主动脉血管内皮间充质转化情况的影响。[方法]将孕鼠随机分为正常饮食组、高脂饮食组,待母鼠分娩后,子代小鼠正常饮食16周。采用Western blot、RT-qPCR检测相关蛋白表达情况,免疫荧光及免疫组织化学染色对小鼠血管行病理分析。[结果]与母亲孕期正常饮食的子代小鼠相比,孕期高脂饮食的子代小鼠血管内炎症分子表达、血管巨噬细胞浸润、单核细胞-内皮层黏附明显增加(P<0.05)。血管内皮型一氧化氮合酶(eNOS)和一氧化氮(NO)水平则显著降低(P<0.05)。对主动脉弓内弯处进行免疫荧光检测,发现孕期高脂饮食子代小鼠内膜上的CD31水平降低,α平滑肌肌动蛋白(α-SMA)则上升。Western blot结果显示母亲孕期高脂饮食子代小鼠血管内膜CD31、血管内皮钙黏蛋白(VE-cadherin)表达降低(P<0.05),α-SMA、波形蛋白的表达增加(P<0.05);同时,母亲孕期高脂饮食子代小鼠主动脉弓内弯处转化生长因子β(TGF-β)/Smad信号活性增强、血管胞外基质的沉积增多。另外,孕期高脂饮食后,其子代血管的Krüppel样因子2(KLF2)的mRNA和蛋白表达均分别降低了76%和59%。[结论]孕期高脂饮食可以导致其子代主动脉血管内皮间充质发生转变。该结果对动脉粥样硬化等血管性疾病的早期预防具有一定的意义。Aim To study the effect of maternal high-fat diet during pregnancy on endothelial to mesenchymal transition of aortic vessels in adult offspring.Methods The pregnant mice were randomly divided into normal diet group and high-fat diet group,and the offspring mice were fed normally for 16 weeks after the mother gave birth.Western blot and RT-qPCR were used to detect the expression and transcription of related proteins,and immunofluorescence and im-munohistochemical staining were used for pathological analysis.Results Compared with the offspring of maternal nor-mal diet during pregnancy,the expressions of vascular inflammatory factors,macrophage infiltration,monocyte-endothelium adhesion were significantly increased in the offspring of maternal high-fat diet(OHF)during pregnancy(P<0.05).Vas-cular endothelial nitric oxide synthase(eNOS)activity,nitric oxide(NO)level were dramatically reduced(P<0.05).Immunofluorescence results showed reduced endothelial cell marker CD31 and increased mesenchymal markerα-smooth muscle actin(α-SMA)in OHF.Western blot analysis further confirmed the results,which showed that maternal high fat diet reduced vascular endothelial-cadherin(VE-cadherin)and CD31 and increasedα-SMA and Vimentin in the offspring(P<0.05).The maternal high fat diet increased the extracellular matrix protein disposition and transforming growth factor beta(TGF-β)/Smad signaling in endothelium(P<0.05).Moreover,the maternal high fat diet reduced Kruppel-like factor 2(KLF2)expression by 76%in mRNA level and 59%in protein level(P<0.05).Conclusion Maternal high-fat diet during pregnancy lead to a transition of endothelial to mesenchyme in the offspring aorta.The results provide a clue for prevention of vascular disease in early stage.

关 键 词：高脂饮食 内皮间充质转化 Krüppel样因子2 小鼠 母亲孕期 子代 

分 类 号：R5[医药卫生—内科学] R363[医药卫生—临床医学]