Pan Xiaoyu, Jia Zhuoya, Zhen Ruoxi, Yue Lin, Niu Shu, Ban Jiangli, Chen Shuchun
Department of Internal Medicine, Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei, People's Republic of China.
Diabetes Metab Syndr Obes. 2023 Jun 28;16:1941-1952. doi: 10.2147/DMSO.S421650. eCollection 2023.
Studies have shown that atherosclerotic plaques are associated with changes in the microbial composition of the intestinal flora and obesity, and that the small intestine plays an irreplaceable role in regulating intestinal flora homeostasis, but the role of the small intestine in the development of obesity-related atherosclerosis remains understudied. Therefore, this study explores the role of the small intestine in obesity-induced atherosclerosis and its molecular mechanisms.
In the GSE59054 data, small intestine tissue samples from 3 normal and 3 obese mice were analyzed using bioinformatics methods. Screening for differentially expressed genes (DEGs) using the GEO2R tool. The DEGs were next processed for bioinformatics analysis. We constructed an obese mouse model and measured aortic arch pulse wave velocity (PWV). Aortic and small intestine tissues were stained with hematoxylin-eosin (HE) to observe pathological changes. Finally, immunohistochemistry was performed to verify the expression of small intestinal proteins.
We identified a total of 122 DEGs. Pathway analysis revealed that BMP4, CDH5, IL1A, NQO1, GSTM1, GSTA3, CAV1 and MGST2 were mainly enriched in the Fluid shear stress and atherosclerosis pathway. In addition, BMP4, NQO1 and GSTM1 are closely related to atherosclerosis. Ultrasound and pathological findings suggest the presence of obesity atherosclerosis. Immunohistochemistry verified high expression of BMP4 and low expression of NQO1 and GSTM1 in obese small intestine tissues.
The altered expression of BMP4, NQO1 and GSTM1 in small intestine tissues during obesity may be related to atherosclerosis, and Fluid shear stress and atherosclerosis pathway may be the molecular mechanism of their role.
研究表明，动脉粥样硬化斑块与肠道菌群微生物组成变化及肥胖有关，且小肠在调节肠道菌群稳态中发挥着不可替代的作用，但小肠在肥胖相关动脉粥样硬化发生发展中的作用仍研究不足。因此，本研究探讨小肠在肥胖诱导的动脉粥样硬化中的作用及其分子机制。
在GSE59054数据中，使用生物信息学方法分析3只正常小鼠和3只肥胖小鼠的小肠组织样本。使用GEO2R工具筛选差异表达基因（DEG）。接下来对DEG进行生物信息学分析。我们构建了肥胖小鼠模型并测量主动脉弓脉搏波速度（PWV）。用苏木精-伊红（HE）对主动脉和小肠组织进行染色以观察病理变化。最后，进行免疫组织化学以验证小肠蛋白的表达。
我们共鉴定出122个DEG。通路分析显示，BMP4、CDH5、IL1A、NQO1、GSTM1、GSTA3、CAV1和MGST2主要富集在流体切应力与动脉粥样硬化通路中。此外，BMP4、NQO1和GSTM1与动脉粥样硬化密切相关。超声和病理结果提示存在肥胖性动脉粥样硬化。免疫组织化学证实肥胖小肠组织中BMP4高表达，NQO1和GSTM1低表达。
肥胖期间小肠组织中BMP4、NQO1和GSTM1表达的改变可能与动脉粥样硬化有关，流体切应力与动脉粥样硬化通路可能是其发挥作用的分子机制。
