Page 81 - 南京医科大学学报自然科学版

第43卷第5期 南京医科大学学报（自然科学版）
2023年5月 Journal of Nanjing Medical University（Natural Sciences） ·663 ·

·基础研究·

高脂饮食通过小肠上皮组织外泌体促进心脏纤维化

赫义君，盛云露，夏 凡，丁国宪 *
南京医科大学第一附属医院老年医学科，江苏 南京 210029

［摘 要］ 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。
［关键词］ 高脂饮食；小肠上皮组织外泌体；心脏纤维化；心脏成纤维细胞
［中图分类号］ R329.26 ［文献标志码］ A ［文章编号］ 1007⁃4368（2023）05⁃663⁃06
doi：10.7655/NYDXBNS20230511

Highfat diet promotes cardiac fibrosis through exosomes from small intestinal epithelium

*
HE Yijun，SHENG Yunlu，XIA Fan，DING Guoxian
Department of Geriatric Endocrinology，the First Affiliated Hospital of Nanjing Medical University，Nanjing 210029，
China

［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.
［Key words］ high fat diet；exosomes from small intestinal epithelium；myocardial fibrosis；cardiac fibroblasts
［J Nanjing Med Univ，2023，43（05）：663⁃668］

随着当今社会经济快速发展，人们的饮食习惯 为全世界的健康难题，不仅影响美观，更能引起心
也在不断变化，开始摄入越来越多高能量、高脂肪 脏纤维化，进而导致病理性心肌重构、心脏舒张功
［1］
的食物。这种不良的饮食方式造成的肥胖逐渐成 能和收缩功能进行性下降，最终导致心力衰竭 。
研究发现，高脂饮食（high fat diet，HFD）饲喂小鼠8周

［基金项目］ 国家自然科学基金（81801383，82071579） 即可诱发小鼠心脏组织中Ⅰ型、Ⅲ型胶原沉积，IL⁃6、
［2］
∗
通信作者（Corresponding author），E⁃mail：dinggx@njmu.edu.cn IL⁃1β、TNF⁃α等炎症因子表达升高 ；而饲喂 18~