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文章:

小鼠肝细胞癌模型中微血管结构的高分辨率定量重建

High-Resolution Quantitative Reconstruction of Microvascular Architectures in Mouse Hepatocellular Carcinoma Models

原文发布日期:14 August 2025

DOI: 10.3390/cancers17162653

类型: Article

开放获取: 是

 

英文摘要:

Background/Objectives: Alterations in liver vascularization play a remarkable role in liver disease development, including hepatocellular carcinoma (HCC), but remain understudied. This study evaluated the hepatic microvascular imaging method and provided high-resolution quantitative anatomical data on the characteristics and architecture of liver vasculature in wild-type (WT) mice and HCC mouse models.Methods: C57BL/6 mice were injected with Akt/Ras or Sleeping Beauty transposon to induce HCC. Liver tissues from normal and Akt/Ras mice underwent hematoxylin and eosin, Masson’s trichrome, Ki67, and lymphatic endothelial receptor-1 staining. Using cutting-edge high-definition fluorescence micro-optical sectioning tomography, high-precision microvascular visualization of the liver was performed in WT and Akt/Ras HCC mice.Results: The sectioned volumes of normal and HCC liver tissues were 204.8 mm3and 212.8 mm3, respectively. The microvascular systems associated with the tissues of the Akt/Ras HCC mouse were twisted, disordered, and compressed by tumor nodules. In the four tumor nodules, the path of the hepatic artery was more around the tumor edge, whereas the portal vein occupied the central position and constituted the main blood vessel entering the tumors. The porosity of HCC and paracancerous cirrhotic tissues was significantly less than that of normal tissues. The radii of the central vessels in the hepatic sinusoid of paratumoral cirrhotic tissues were significantly higher than those of normal tissues; however, the hepatic sinusoid density of paratumoral cirrhotic tissues was lower.Conclusions: This research provides a deeper understanding of the normal liver microvasculature and alterations in cases of cirrhosis and HCC, which complements scientific insights into liver morphology and physiology. This straightforward research approach involving the novel 3D liver microvasculature can be used in multiscale physiological and pathophysiological studies regarding liver diseases.

 

摘要翻译: 

背景/目的:肝脏血管化改变在肝病(包括肝细胞癌)发展中扮演重要角色,但相关研究仍不充分。本研究评估了肝脏微血管成像方法,并提供了野生型小鼠及肝细胞癌小鼠模型中肝脏血管系统特征与结构的高分辨率定量解剖数据。方法:通过注射Akt/Ras或睡美人转座子诱导C57BL/6小鼠形成肝细胞癌。对正常小鼠和Akt/Ras小鼠肝组织进行苏木精-伊红染色、Masson三色染色、Ki67及淋巴管内皮受体-1染色。采用前沿的高清荧光显微光学切片断层成像技术,对野生型和Akt/Ras肝细胞癌小鼠肝脏进行高精度微血管可视化成像。结果:正常与肝细胞癌肝组织切片体积分别为204.8 mm³和212.8 mm³。Akt/Ras肝细胞癌小鼠组织相关微血管系统呈现扭曲、紊乱状态,并受肿瘤结节压迫。在四个肿瘤结节中,肝动脉路径更多分布于肿瘤边缘,而门静脉占据中心位置,构成进入肿瘤的主要血管。肝细胞癌及癌旁肝硬化组织的孔隙率显著低于正常组织。癌旁肝硬化组织肝血窦中央血管半径显著高于正常组织,但其肝血窦密度较低。结论:本研究深化了对正常肝脏微血管系统及肝硬化、肝细胞癌病理改变的认识,为肝脏形态与生理学研究提供了科学补充。这种基于新型三维肝脏微血管系统的简明研究方法,可应用于肝脏疾病的多尺度生理学与病理生理学研究。

 

 

原文链接:

High-Resolution Quantitative Reconstruction of Microvascular Architectures in Mouse Hepatocellular Carcinoma Models

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