Department of Anatomy, School of Medicine, Kurdistan University of Medical Sciences, Sanandaj, Iran.
Department of Anatomy, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran.
J Cell Biochem. 2018 Feb;119(2):1716-1725. doi: 10.1002/jcb.26331. Epub 2017 Sep 7.
Therapeutic effects of melatonin (MEL) in targeting CCl -induced liver fibrosis has been widely known, but there is no study comparing oxidative and fibrogenic changes in co- and post-treatment of MEL with CCl , which was further aimed in this experiment. Male SD rats were injected with CCl (1 mL/kg/i.p./daily) dissolved 1:1 in olive oil for 1 month. Some animals received MEL (20 mg/kg/i.p./daily) diluted in 1 mL PBS in combination with CCl (co-treatment), and some rats were treated with MEL, beginning with injection of the last dose of CCl for one month (post-treatment). The groups were control, CCl , CCl -co vehicle, CCl -post vehicle, post-CCl , MEL co-treatment, and MEL post-treatment. MEL post-treatment group showed significantly lower lipid deposition, serum malondialdehyde (MDA), serum alanine aminotransferase (ALT), and liver hydroxyproline. This group also had low expressions of Bax and transforming growth factor-β1 (TGF-β1). MEL post-treatment group revealed higher sera levels of albumin, superoxide dismutase (SOD) and glutathione peroxidase (GPx). Expression levels of metalloproteinase-13 (MMP-13) and Bcl2 was also higher in this group (P ≤ 0.05 vs co-treatment). Results of the present study indicated that MEL post-treatment is more powerful in reduction of CCl -induced liver fibrosis through reduction of oxidative stress and maintenance of matrix balance.
褪黑素（MEL）在靶向 CCl 诱导的肝纤维化中的治疗效果已被广泛知晓，但目前尚无研究比较 MEL 与 CCl 共同和序贯治疗时氧化和纤维生成变化，本实验旨在进一步探讨这一问题。雄性 SD 大鼠以橄榄油 1:1 溶解的 CCl （1 mL/kg/ip/天）连续腹腔注射 1 个月。部分动物接受腹腔注射 MEL（20 mg/kg/天）与 CCl 联合治疗（共同治疗组），部分动物于 CCl 末次注射后开始接受 MEL 治疗（1 个月，序贯治疗组）。实验分组为对照组、CCl 组、CCl 共同溶剂组、CCl 序贯溶剂组、CCl 后组、MEL 共同治疗组和 MEL 序贯治疗组。与共同治疗组相比，MEL 序贯治疗组肝组织脂质沉积、血清丙氨酸氨基转移酶（ALT）、血清丙二醛（MDA）、羟脯氨酸含量显著降低，Bax 和转化生长因子-β1（TGF-β1）表达下调。同时，MEL 序贯治疗组血清白蛋白、超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GPx）水平升高，基质金属蛋白酶-13（MMP-13）和 Bcl2 表达上调（与共同治疗组比较，P 均<0.05）。研究结果表明，MEL 序贯治疗通过减轻氧化应激和维持基质平衡，对 CCl 诱导的肝纤维化具有更强的抑制作用。
