Akbari-Kordkheyli Vahid, Azizi Soheil, Khonakdar-Tarsi Abbas
Student Research Committee, Mazandaran University of Medical Sciences, Sari, Iran.
Department of Laboratory Medicine, Faculty of Allied Medical Sciences, Mazandaran University of Medical Sciences, Sari, Iran.
Iran J Basic Med Sci. 2019 Jul;22(7):789-796. doi: 10.22038/ijbms.2019.34967.8313.
Liver ischemia-reperfusion injuries (I/RI) are typically the main causes of liver dysfunction after various types of liver surgery especially liver transplantation. Radical components are the major causes of such direct injuries. We aimed to determine the beneficial effects of silibinin, a potent radical scavenger on liver I/RI.
Thirty-two rats were divided into 4 groups. Group I: VEHICLE, the rats underwent laparotomy and received DMSO, group II: SILI, laparotomy was done and silibinin was administered. Group III: I/R, the rats received DMSO and were subjected to a liver I/R procedure and group IV: I/R+SILI, the animals underwent the I/R procedure and received silibinin. After 1 hr of ischemia followed by 3 hr reperfusion, blood was collected to evaluate the serum marker of liver injuries. Hepatic tissue was harvested to investigate glycogen content, histological changes, and vasoregulatory gene expression.
Results showed that serum AST, ALT, LDH, GGT, ALP, and hyaluronic acid (HA) increased significantly in I/R group compared with the VEHICLE group. Silibinin reduced this elevation except for GGT. Silibinin inhibited hepatocyte vacuolization and degeneration, endothelium damages, sinusoidal congestion and inflammation, and glycogen depletion during I/R. ET-1 mRNA was overproduced in the I/R group compared with the VEHICLE group which was decreased by silibinin. KLF2 and eNOS expression was reduced during I/R compared with the VEHICLE group. Silibinin elevated KLF2 expression but had no meaningful effect on eNOS expression.
Silibinin protected the liver from I/RI. Silibinin could improve liver circulation by preventing sinusoidal congestion, inflammation, and perhaps modification of the vasoregulatory gene expression.
肝缺血再灌注损伤（I/RI）通常是各类肝脏手术尤其是肝移植术后肝功能障碍的主要原因。自由基成分是此类直接损伤的主要原因。我们旨在确定水飞蓟宾（一种有效的自由基清除剂）对肝脏I/RI的有益作用。
32只大鼠分为4组。第一组：载体组，大鼠接受剖腹手术并给予二甲基亚砜（DMSO）；第二组：水飞蓟宾组，进行剖腹手术并给予水飞蓟宾；第三组：I/R组，大鼠接受DMSO并进行肝脏I/R手术；第四组：I/R+水飞蓟宾组，动物进行I/R手术并给予水飞蓟宾。缺血1小时后再灌注3小时，采集血液以评估肝损伤的血清标志物。采集肝组织以研究糖原含量、组织学变化和血管调节基因表达。
结果显示，与载体组相比，I/R组血清天冬氨酸氨基转移酶（AST）、丙氨酸氨基转移酶（ALT）、乳酸脱氢酶（LDH）、γ-谷氨酰转移酶（GGT）、碱性磷酸酶（ALP）和透明质酸（HA）显著升高。除GGT外，水飞蓟宾减轻了这种升高。水飞蓟宾抑制了I/R期间的肝细胞空泡化和变性、内皮损伤、肝血窦充血和炎症以及糖原消耗。与载体组相比，I/R组内皮素-1（ET-1）mRNA过度产生，水飞蓟宾使其降低。与载体组相比，I/R期间Krüppel样因子2（KLF2）和内皮型一氧化氮合酶（eNOS）表达降低。水飞蓟宾提高了KLF2表达，但对eNOS表达无显著影响。
水飞蓟宾可保护肝脏免受I/RI损伤。水飞蓟宾可通过防止肝血窦充血、炎症以及可能对血管调节基因表达的调节来改善肝脏循环。
