Genetic Biology, Islamic Azad University of Tonekabon, Tonekabon, Iran.
Anatomy and Cell Biology Department, Faculty of Medicine, Mazandaran University of Medical Sciences, Sari, Mazandaran, Iran.
Mol Biol Rep. 2020 May;47(5):3271-3280. doi: 10.1007/s11033-020-05383-w. Epub 2020 Apr 5.
The mitochondrial damage has a pivotal role in triggering apoptosis and cell death. This study assessed the effect of silibinin on optical atrophy-1 (OPA1) and mitofusin-1 (MFN1) gene expression in liver tissue during hepatic warm ischemia-reperfusion (IR). Four groups of rats, eight rats each were designed: Vehicle: the rats received normal saline and encountered to laparotomy, Sili: silibinin (60 mg/kg) was administered to animals, IR: the rats received the normal saline and insulted by liver IR procedure, and IR + Sili: silibinin was injected to rats. All groups were subjected to the same process of injection of the solvent or silibinin (30 min before laparotomy or ischemia and immediately after the reperfusion), intraperitoneally (IP). After 3 h of reperfusion, blood and liver tissue samples were collected for future examinations. Our results showed no significant differences between the Vehicle and Sili groups in all assessed parameters. In IR + Sili, the increased serum levels of AST and ALT in comparison with the control group were markedly reduced by silibinin treatment. Silibinin lowered the elevated expression of OPA1 and MFN1 mRNAs in the IR group. Histology revealed silibinin could decline tissue degeneration compared to the IR group. Electron microscopy of control and silibinin groups showed no fusion of mitochondria and tissue degradation both of which were observed in the IR group. The extent of tissue destruction and mitochondrial fusion decreased significantly with silibinin treatment. Silibinin has a protective effect on liver cells against IR induced injuries by preserving mitochondrial membrane.
线粒体损伤在触发细胞凋亡和死亡中起着关键作用。本研究评估了水飞蓟宾对肝热缺血再灌注(IR)过程中肝组织中光学萎缩-1(OPA1)和线粒体融合蛋白-1(MFN1)基因表达的影响。设计了四组大鼠,每组 8 只:对照组:大鼠接受生理盐水处理,并进行剖腹手术;Sili 组:给予大鼠水飞蓟宾(60mg/kg);IR 组:大鼠接受生理盐水处理,并受到肝 IR 过程的损伤;IR+Sili 组:水飞蓟宾注射至大鼠。所有组均接受相同的溶剂或水飞蓟宾注射过程(剖腹手术或缺血前 30 分钟和再灌注后立即进行),腹膜内(IP)。再灌注 3 小时后,采集血液和肝组织样本进行进一步检查。我们的结果表明,在所有评估参数中,对照组和 Sili 组之间没有显著差异。与对照组相比,IR+Sili 组大鼠血清中天冬氨酸转氨酶(AST)和丙氨酸转氨酶(ALT)水平升高,而水飞蓟宾治疗明显降低了这些升高的酶水平。水飞蓟宾降低了 IR 组 OPA1 和 MFN1 mRNA 的表达水平。组织学显示,与 IR 组相比,水飞蓟宾组可减少组织退化。电镜观察发现,与对照组相比,IR 组线粒体融合和组织降解,而在水飞蓟宾组则未观察到这两种情况。水飞蓟宾治疗后,组织破坏和线粒体融合的程度显著降低。水飞蓟宾通过维持线粒体膜对肝细胞具有保护作用,防止 IR 引起的损伤。