Department of Radiology, Second Xiangya Hospital of Central South University, Changsha, Hunan 410011, P.R. China.
Department of Radiology, The Second People's Hospital of Hunan Province, Changsha, Hunan 410007, P.R. China.
Mol Med Rep. 2021 Sep;24(3). doi: 10.3892/mmr.2021.12310. Epub 2021 Jul 23.
Hepatic ischemia/reperfusion injury (HIRI) is a complex pathophysiological process that may develop after liver transplantation and resection surgery, as well as in uncontrolled clinical conditions. Bone marrow‑derived mesenchymal stem cells (BM‑MSCs) are potential targets for liver diseases. Thus, the present study aimed to investigate the effects of superoxide dismutase 2 (SOD2) overexpression in BM‑MSCs on HIRI by constructing a HIRI rat model. The adenoviral vector containing SOD2 and the corresponding control vector were designed and constructed, and SOD2‑overexpressing BM‑MSCs were injected into the tail vein of the rats. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, as well as pathological changes and the remnant liver regeneration rate were determined. The activities of SOD and glutathione peroxidase (GSH‑Px), and malondialdehyde (MDA) content were measured. Reactive oxygen species (ROS) were determined with 2',7'‑-dichlorofluorescein diacetate and measured via fluorescence microscopy. Cell apoptosis was assessed using TUNEL staining. Moreover, the expression levels of Bax, Bcl‑2 and caspase‑3 were detected via western blotting. SOD2‑overexpressing BM‑MSCs significantly reduced the elevation of serum AST and ALT levels. Furthermore, SOD2‑overexpressing BM‑MSCs enhanced SOD and GSH‑Px activities, and suppressed the production of MDA and ROS. Histopathological findings revealed that SOD2‑overexpressing BM‑MSCs decreased the number of TUNEL‑positive cells in the liver. It was also found that SOD2‑overexpressing BM‑MSCs promoted Bcl‑2 expression, but inhibited Bax and caspase‑3 expression in HIRI. Collectively, these findings suggest that SOD2‑overexpressing BM‑MSCs may provide therapeutic support in HIRI by inhibiting oxidative stress and hepatocyte apoptosis.
肝缺血/再灌注损伤（HIRI）是一种复杂的病理生理过程，可能发生在肝移植和切除术以及不受控制的临床情况下。骨髓间充质干细胞（BM-MSCs）是肝脏疾病的潜在靶点。因此，本研究旨在通过构建 HIRI 大鼠模型来探讨过表达超氧化物歧化酶 2（SOD2）的 BM-MSCs 对 HIRI 的影响。设计并构建了含有 SOD2 的腺病毒载体和相应的对照载体，并将 SOD2 过表达的 BM-MSCs 注入大鼠尾静脉。测定天冬氨酸氨基转移酶（AST）和丙氨酸氨基转移酶（ALT）水平以及肝组织病理学变化和剩余肝再生率。测定 SOD 和谷胱甘肽过氧化物酶（GSH-Px）的活性以及丙二醛（MDA）含量。使用 2'，7'-二氯荧光素二乙酸酯测定活性氧（ROS）并通过荧光显微镜进行测量。使用 TUNEL 染色评估细胞凋亡。此外，通过 Western blot 检测 Bax、Bcl-2 和 caspase-3 的表达水平。SOD2 过表达的 BM-MSCs 显著降低了血清 AST 和 ALT 水平的升高。此外，SOD2 过表达的 BM-MSCs 增强了 SOD 和 GSH-Px 的活性，并抑制了 MDA 和 ROS 的产生。组织病理学发现表明，SOD2 过表达的 BM-MSCs 减少了肝中 TUNEL 阳性细胞的数量。还发现 SOD2 过表达的 BM-MSCs 促进了 Bcl-2 的表达，但抑制了 HIRI 中 Bax 和 caspase-3 的表达。综上所述，这些发现表明 SOD2 过表达的 BM-MSCs 可能通过抑制氧化应激和肝细胞凋亡为 HIRI 提供治疗支持。
