Abdelsameea Ahmed A, Abbas Noha A T, Abdel Raouf Samar M
Department of Pharmacology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
Department of Pathology, Faculty of Medicine-Zagazig University, Zagazig, Egypt.
Naunyn Schmiedebergs Arch Pharmacol. 2017 Mar;390(3):311-319. doi: 10.1007/s00210-016-1330-7. Epub 2016 Dec 16.
Ischemia-reperfusion (IR) injury constitutes the most important cause of primary dysfunction of liver grafts. In this study, we have addressed the possible hepatoprotective action of liraglutide against partial warm hepatic IR injury in male rats. Rats were randomly assigned into: sham, IR, and liraglutide-pretreated IR groups. Liraglutide was administered 50 μg/kg s.c. twice daily for 14 days, and then, hepatic IR was induced by clamping portal vein and hepatic artery to left and median lobes for 30 min followed by reperfusion for 24 h. Serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma glutamyl transferase (GGT) activities were determined. Malondialdehyde (MDA) level, reduced glutathione (GSH) content, tumor necrosis factor-α (TNF-α), phosphoralated Akt (p-Akt), and caspase-3 levels of the liver were determined. Hematoxylin and eosin (H&E) stained sections from liver were examined as well as immunohistochemical sections for detection of Bcl-2 expression. IR injury increased ALT, AST, and GGT while decreased GSH and p-Akt with increase in MDA, TNF-α, and caspase-3 levels in the liver with necrosis and inflammatory cellular infiltration with decreased Bcl-2 expression. Pretreatment with liraglutide decreased ALT, AST, and GGT activities while increased glutathione content and Akt activation with decrements in MDA, TNF-α, and caspase-3 levels with attenuation of necrosis and inflammation while enhanced Bcl-2 expression in the liver. Liraglutide protects against IR injury of the liver through antiinflammatory and antioxidant actions as well as inhibition of apoptosis.
缺血再灌注（IR）损伤是肝移植原发性功能障碍的最重要原因。在本研究中，我们探讨了利拉鲁肽对雄性大鼠部分肝脏热缺血再灌注损伤可能的肝保护作用。将大鼠随机分为：假手术组、IR组和利拉鲁肽预处理的IR组。利拉鲁肽以50μg/kg皮下注射，每日两次，共14天，然后通过夹闭门静脉和肝动脉至左叶和中叶30分钟，随后再灌注24小时诱导肝脏IR。测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和γ-谷氨酰转移酶（GGT）活性。测定肝脏丙二醛（MDA）水平、还原型谷胱甘肽（GSH）含量、肿瘤坏死因子-α（TNF-α）、磷酸化Akt（p-Akt）和半胱天冬酶-3水平。检查肝脏苏木精和伊红（H&E）染色切片以及用于检测Bcl-2表达的免疫组织化学切片。IR损伤增加了ALT、AST和GGT，同时降低了GSH和p-Akt，肝脏中MDA、TNF-α和半胱天冬酶-3水平升高，伴有坏死和炎性细胞浸润，Bcl-2表达降低。利拉鲁肽预处理降低了ALT、AST和GGT活性，同时增加了谷胱甘肽含量和Akt激活，MDA、TNF-α和半胱天冬酶-3水平降低，坏死和炎症减轻，同时肝脏中Bcl-2表达增强。利拉鲁肽通过抗炎和抗氧化作用以及抑制细胞凋亡来保护肝脏免受IR损伤。
