高脂饮食通过小肠上皮组织外泌体促进心脏纤维化
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国家自然科学基金(81801383,82071579)


Highfat diet promotes cardiac fibrosis through exosomes from small intestinal epithelium
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    目的:研究高脂饮食通过小肠上皮组织外泌体对小鼠心脏成纤维细胞增殖、分化、胶原蛋白合成的影响。方法:分别提取正常饮食/高脂饮食小鼠小肠上皮组织外泌体,与小鼠原代心脏成纤维细胞共培养,PKH26标记外泌体,示踪观察心脏成纤维细胞对外泌体的摄取情况;对心脏成纤维细胞进行荧光定量PCR,观察增殖、分化、纤维化、炎症等基因表达;利用免疫荧光染色观察心脏成纤维细胞α平滑肌肌动蛋白(alpha smooth muscleactin,α-SMA)、Ⅰ型、Ⅲ型胶原蛋白表达。结果:正常/高脂饮食小鼠小肠上皮组织外泌体均可被心脏成纤维细胞摄取,且两者摄取效率无差异。相比正常饮食组,高脂饮食小鼠小肠上皮组织外泌体可显著增加心脏成纤维细胞增殖分化、细胞外基质积聚、炎症等基因表达,合成α-SMA蛋白、Ⅰ型、Ⅲ型胶原蛋白能力增强。结论:高脂饮食可以通过小肠上皮组织外泌体促进心脏成纤维细胞增殖、分化及胶原产生。

    Abstract:

    Objective:To study the effects of high fat diet on the proliferation,differentiation and collagen synthesis of mouse cardiac fibroblasts through exosomes from small intestinal epithelium. Methods:Exosomes from small intestinal epithelium of normal/ high fat diet mice were extracted and co-cultured with primary mouse cardiac fibroblasts. Exosomes uptake of cardiac fibroblasts of the two groups was observed by PKH26 labeling,and the gene expressions of proliferation,differentiation,fibrosis and inflammation of cardiac fibroblasts were determined by PCR. Immunofluorescence staining was used to observe the expression of α-SMA,Col1a1 and Col3a1 in cardiac fibroblasts of the two groups. Results:The exosomes from small intestinal epithelium of normal/high -fat diet mice could be absorbed by cardiac fibroblasts,and there was no difference in uptake efficiency between them. Compared with the normal diet group,the small intestinal exosomes of mice fed with high fat diet could significantly increase the gene expression of cardiac fibroblasts,such as genes associated with proliferation,differentiation,extracellular matrix accumulation and inflammation,and enhance the ability to synthesize α - SMA,Col1a1 and Col3a1 protein. Conclusion:High fat diet can promote the proliferation, differentiation and collagen production of cardiac fibroblasts through exosomes from small intestinal epithelium.

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赫义君,盛云露,夏凡,丁国宪.高脂饮食通过小肠上皮组织外泌体促进心脏纤维化[J].南京医科大学学报(自然科学版),2023,(5):663-668

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  • 收稿日期:2023-01-30
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  • 在线发布日期: 2023-05-18
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