Ciftel Sedat, Mercantepe Tolga, Aktepe Riza, Pinarbas Esra, Ozden Zulkar, Yilmaz Adnan, Mercantepe Filiz
Department of Gastroenterology and Hepatology, Erzurum Regional Education and Research Hospital, 25070 Erzurum, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey.
Biomedicines. 2024 Oct 10;12(10):2299. doi: 10.3390/biomedicines12102299.
BACKGROUND/OBJECTIVES: Acute mesenteric ischemia can lead to severe liver damage due to ischemia-reperfusion (I/R) injury. This study investigated the protective effects of trimetazidine (TMZ) and dexmedetomidine (DEX) against liver damage induced by mesenteric artery I/R via endoplasmic reticulum stress (ERS) mechanisms.
Twenty-four rats were divided into four groups: control, I/R, I/R+TMZ, and I/R+DEX. TMZ (20 mg/kg) was administered orally for seven days, and DEX (100 µg/kg) was given intraper-itoneally 30 min before I/R induction. Liver tissues were analyzed for creatinine, alanine ami-notransferase (ALT), aspartate aminotransferase (AST), thiobarbituric acid reactive substances (TBARS), and total thiol (TT) levels.
Compared with the control group, the I/R group presented significantly increased AST, ALT, TBARS, and TT levels. TMZ notably reduced creatinine levels. I/R caused significant liver necrosis, inflammation, and congestion. TMZ and DEX treatments reduced this histopathological damage, with DEX resulting in a more significant reduction in infiltrative areas and vascular congestion. The increase in the expression of caspase-3, Bax, 8-OHdG, C/EBP homologous protein (CHOP), and glucose-regulated protein 78 (GRP78) decreased with the TMZ and DEX treatments. In addition, Bcl-2 positivity decreased both in the TMZ and DEX treatments.
Both TMZ and DEX have protective effects against liver damage. These effects are likely mediated through the reduction in ERS and apoptosis, with DEX showing slightly superior protective effects compared with TMZ.
背景/目的：急性肠系膜缺血可因缺血再灌注（I/R）损伤导致严重肝损伤。本研究通过内质网应激（ERS）机制，探讨曲美他嗪（TMZ）和右美托咪定（DEX）对肠系膜动脉I/R所致肝损伤的保护作用。
将24只大鼠分为四组：对照组、I/R组、I/R+TMZ组和I/R+DEX组。TMZ（20mg/kg）口服给药7天，DEX（100μg/kg）在诱导I/R前30分钟腹腔注射。分析肝组织中的肌酐、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、硫代巴比妥酸反应性物质（TBARS）和总巯基（TT）水平。
与对照组相比，I/R组的AST、ALT、TBARS和TT水平显著升高。TMZ显著降低肌酐水平。I/R导致明显的肝坏死、炎症和充血。TMZ和DEX治疗减轻了这种组织病理学损伤，DEX使浸润区域和血管充血的减轻更为显著。TMZ和DEX治疗后，半胱天冬酶-3、Bax、8-羟基脱氧鸟苷、C/EBP同源蛋白（CHOP）和葡萄糖调节蛋白78（GRP78）的表达增加有所减少。此外，TMZ和DEX治疗中Bcl-2阳性率均降低。
TMZ和DEX对肝损伤均有保护作用。这些作用可能是通过减少ERS和细胞凋亡介导的，与TMZ相比，DEX的保护作用略优。
