Yang Lin, Xia Bing, Qian Tianbao, Wang Jie, Wang Yuanhe, Dai Jialin, Le Cuiyun, Yang Xiaorong, Wu Jun, Wu Wenxin, Xu Jianwei, Liu Youbin, Wang Jiawen
School of Forensic Medicine, Guizhou Medical University, Guiyang, 550000, Guizhou, China.
School of Biology and Engineering, Guizhou Medical University, Guiyang, 550000, Guizhou, China.
Heliyon. 2024 Sep 28;10(21):e38698. doi: 10.1016/j.heliyon.2024.e38698. eCollection 2024 Nov 15.
The mechanism underlying human umbilical cord mesenchymal stem cells (hUC-MSCs) regulating the stability of atherosclerotic plaque was explored by establishing mice models of atherosclerosis induced by a high-fat diet and hUC-MSCs intervention.
The ApoE mice atherosclerosis model was constructed using a high-fat diet, and mice were divided into a normal diet group (ND), high-fat diet group (HFD), hUC-MSCs treatment group (HFDM), while the blank control (BC) consisted of C57BL/6J mice. After successful establishment of the model, the feces, hearts, and aorta of mice were collected. Morphological features were detected using HE, oil red O, and Masson staining. Afterward, 16s rRNA gene sequences was used to detect the species and abundance of the intestinal flora in mice, and an atomic force microscope (AFM) was used to detect the Young's modulus of the fibrous cap of atherosclerotic plaques. Lastly, the expression level of the inflammatory factors NLRP3, IL-1β, and IL-18 were detected via immunohistochemistry and immunofluorescence assays.
In terms of morphological characteristics, the expression level of NLRP3, Young's modulus of the fibrous cap, and plaque stability were significantly reduced in HFD, whereas the ratio of Firmicutes to Bacteroidetes (F/B) was significantly increased. Interestingly, hUC-MSCs treatment reversed the above indices, thus enhancing plaque stability.
HFD led to dysregulation of intestinal flora homeostasis and induced aberrant expression levels of NLRP3, resulting in a decrease in the Young's modulus of plaques. However, hUC-MSCs treatment improved the biomechanical properties of plaque by modulating the intestinal flora and NLRP3, thereby elevating plaque stability and minimizing the risk of plaque rupture.
通过建立高脂饮食诱导的动脉粥样硬化小鼠模型及人脐带间充质干细胞（hUC-MSCs）干预，探讨hUC-MSCs调节动脉粥样硬化斑块稳定性的机制。
采用高脂饮食构建ApoE小鼠动脉粥样硬化模型，将小鼠分为正常饮食组（ND）、高脂饮食组（HFD）、hUC-MSCs治疗组（HFDM），空白对照组（BC）为C57BL/6J小鼠。模型成功建立后，收集小鼠粪便、心脏和主动脉。采用苏木精-伊红（HE）、油红O和Masson染色检测形态学特征。随后，利用16s rRNA基因序列检测小鼠肠道菌群的种类和丰度，并用原子力显微镜（AFM）检测动脉粥样硬化斑块纤维帽的杨氏模量。最后，通过免疫组织化学和免疫荧光分析检测炎症因子NLRP3、白细胞介素-1β（IL-1β）和白细胞介素-18（IL-18）的表达水平。
在形态学特征方面，高脂饮食组中NLRP3的表达水平、纤维帽的杨氏模量和斑块稳定性显著降低，而厚壁菌门与拟杆菌门的比例（F/B）显著增加。有趣的是，hUC-MSCs治疗逆转了上述指标，从而增强了斑块稳定性。
高脂饮食导致肠道菌群稳态失调，诱导NLRP3表达异常，导致斑块杨氏模量降低。然而，hUC-MSCs治疗通过调节肠道菌群和NLRP3改善了斑块的生物力学性能，从而提高了斑块稳定性，降低了斑块破裂的风险。
