Sheen Jiunn-Ming, Chen Yu-Chieh, Hsu Mei-Hsin, Tain You-Lin, Huang Ying-Hsien, Tiao Mao-Meng, Li Shih-Wen, Huang Li-Tung
Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta-Pei Road, Niao Sung, Kaohsiung 833, Taiwan.
Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Linkou, Taoyuan 333, Taiwan.
Int J Mol Sci. 2016 Aug 20;17(8):1365. doi: 10.3390/ijms17081365.
Bile duct ligation (BDL)-treated rats display cholestasis and liver damages. The potential protective activity of melatonin in young BDL rats in terms of apoptosis, mitochondrial function, and endoplasmic reticulum (ER) homeostasis has not yet been evaluated. Three groups of young male Sprague-Dawley rats were used: one group received laparotomy (Sham), a second group received BDL for two weeks (BDL), and a third group received BDL and intraperitoneal melatonin (100 mg/day) for two weeks (BDL + M). BDL group rats showed liver apoptosis, increased pro-inflamamtory mediators, caspases alterations, anti-apoptotic factors changes, and dysfunction of ER homeostasis. Melatonin effectively reversed apoptosis, mainly through intrinsic pathway and reversed ER stress. In addition, in vitro study showed melatonin exerted its effect mainly through the melatonin 2 receptor (MT2) in HepG2 cells. In conclusion, BDL in young rats caused liver apoptosis. Melatonin rescued the apoptotic changes via the intrinsic pathway, and possibly through the MT2 receptor. Melatonin also reversed ER stress induced by BDL.
胆管结扎（BDL）处理的大鼠表现出胆汁淤积和肝损伤。褪黑素对年轻BDL大鼠在细胞凋亡、线粒体功能和内质网（ER）稳态方面的潜在保护作用尚未得到评估。使用了三组年轻雄性Sprague-Dawley大鼠：一组接受剖腹手术（假手术组），第二组接受BDL手术两周（BDL组），第三组接受BDL手术并腹腔注射褪黑素（100毫克/天）两周（BDL + M组）。BDL组大鼠表现出肝细胞凋亡、促炎介质增加、半胱天冬酶改变、抗凋亡因子变化以及ER稳态功能障碍。褪黑素有效地逆转了细胞凋亡，主要通过内源性途径，并逆转了内质网应激。此外，体外研究表明褪黑素主要通过HepG2细胞中的褪黑素2受体（MT2）发挥作用。总之，幼鼠的BDL导致肝细胞凋亡。褪黑素通过内源性途径挽救了凋亡变化，可能是通过MT2受体。褪黑素还逆转了BDL诱导的内质网应激。
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