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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.

作者信息

Zhao Yan, Zhao Haogang, Wang Xin, Dai Wei, Ren Xuhua, Wang Jing, Cai Guohong

机构信息

Department of Liver Diseases and Interventional Radiology, Xi'an International Medical Center Hospital, Northwest University, Xi'an 710100, China.

State Key Laboratory for Manufacturing Systems Engineering, Xi'an 710054, China.

出版信息

Cancers (Basel). 2025 Aug 14;17(16):2653. doi: 10.3390/cancers17162653.

Abstract

: 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. : 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. : The sectioned volumes of normal and HCC liver tissues were 204.8 mm and 212.8 mm, 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. : 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

肝脏血管生成的改变在包括肝细胞癌(HCC)在内的肝脏疾病发展中起着显著作用,但仍未得到充分研究。本研究评估了肝脏微血管成像方法,并提供了野生型(WT)小鼠和HCC小鼠模型中肝脏血管系统特征和结构的高分辨率定量解剖数据。:将Akt/Ras或睡美人转座子注射到C57BL/6小鼠体内以诱导HCC。对正常和Akt/Ras小鼠的肝脏组织进行苏木精和伊红染色、Masson三色染色、Ki67染色和淋巴管内皮受体-1染色。使用前沿的高清荧光显微光学切片断层扫描技术,对WT和Akt/Ras HCC小鼠的肝脏进行了高精度微血管可视化。:正常和HCC肝脏组织的切片体积分别为204.8立方毫米和212.8立方毫米。与Akt/Ras HCC小鼠组织相关的微血管系统扭曲、紊乱,并被肿瘤结节压缩。在四个肿瘤结节中,肝动脉路径更多地围绕肿瘤边缘,而门静脉占据中心位置并构成进入肿瘤的主要血管。HCC和癌旁肝硬化组织的孔隙率明显低于正常组织。癌旁肝硬化组织肝血窦中央血管半径明显高于正常组织;然而,癌旁肝硬化组织的肝血窦密度较低。:本研究为正常肝脏微血管以及肝硬化和HCC病例中的改变提供了更深入的理解,补充了对肝脏形态和生理学的科学认识。这种涉及新型3D肝脏微血管的直接研究方法可用于肝脏疾病的多尺度生理和病理生理研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a310/12385133/f2f0ce1b0142/cancers-17-02653-g001.jpg

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