Department of Basic Sciences, School of Veterinary Medicine, Shiraz University, Shiraz, Iran.
Organ Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Iran J Allergy Asthma Immunol. 2021 Feb 11;20(1):88-97. doi: 10.18502/ijaai.v20i1.5415.
Ischemia/reperfusion (I/R) injury in cadaveric liver transplantation is not avoidable. Liver I/R injury is an important phenomenon in hepatic damage. MicroRNA-21 (miR-21) plays an important role in I/R injury. The present study aimed to determine the expression pattern of miR-21 in liver I/R injury/recovery and its correlation with the immunologic transmission signals pathways several days post-reperfusion. In an animal model for I/R in the liver, 40 male Balb/c mice were divided into 3 groups. The animals were monitored for 3 and 24 hours, and also for 4, 7, 14, and 28 days post-reperfusion. Liver tissue damage was assessed by histopathology. The plasma alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total antioxidant capacity (TAC) levels were measured with enzymatic assays. MiR-21, programmed cell death 4 (PDCD4) mRNA, T-cell-restricted intracellular antigen 1 (TIA1) mRNA, and fas ligand (FASL) mRNA expression levels were measured; using reverse transcription-polymerase chain reaction (RT-PCR) at different times after the reperfusion in liver tissue and blood. Histopathology and plasma ALT, AST, ALP, and TAC levels confirmed liver damage induced by I/R injury. MiR-21 increased by twofold in the liver tissue and on the inflammatory phase after 24 hours of reperfusion; it then continued to decrease up to day 7 post-reperfusion. Afterward, it continued to rise slightly up to day 14 post-reperfusion. This trend was in parallel with the recovery of the liver damage. MiR-21 expression level in the liver and blood is a predictor of the extent of I/R injury.
在尸体供肝移植中，缺血再灌注（I/R）损伤是不可避免的。肝 I/R 损伤是肝损伤的重要现象。微小 RNA-21（miR-21）在 I/R 损伤中发挥重要作用。本研究旨在确定 miR-21 在肝 I/R 损伤/恢复中的表达模式及其与再灌注后数天免疫传递信号通路的相关性。在肝 I/R 的动物模型中，将 40 只雄性 Balb/c 小鼠分为 3 组。动物在 3 和 24 小时以及再灌注后 4、7、14 和 28 天进行监测。通过组织病理学评估肝组织损伤。通过酶法测定血浆丙氨酸氨基转移酶（ALT）、天冬氨酸氨基转移酶（AST）、碱性磷酸酶（ALP）和总抗氧化能力（TAC）水平。使用逆转录-聚合酶链反应（RT-PCR）测量 miR-21、程序性细胞死亡因子 4（PDCD4）mRNA、T 细胞限制性细胞内抗原 1（TIA1）mRNA 和 Fas 配体（FASL）mRNA 的表达水平，在再灌注后不同时间在肝组织和血液中。组织病理学和血浆 ALT、AST、ALP 和 TAC 水平证实了 I/R 损伤引起的肝损伤。miR-21 在肝组织中增加了两倍，并在再灌注后 24 小时的炎症期增加；然后继续下降至再灌注后第 7 天。之后，它继续略微上升至再灌注后第 14 天。这种趋势与肝损伤的恢复平行。肝和血液中 miR-21 的表达水平是 I/R 损伤程度的预测指标。
