Department of Gastroenterology, First Affiliated Hospital of Anhui Medical University, Key Laboratory of Digestive Disease of Anhui Province, Hefei, 230022, China.
Department of Critical Care Medicine of Cardiothoracic Surgery, First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China.
Curr Med Sci. 2022 Jun;42(3):498-504. doi: 10.1007/s11596-022-2530-7. Epub 2022 May 17.
Melatonin has been reported to suppress inflammation and alleviate liver fibrosis, but its effect on autophagy in liver fibrosis has not been studied. This study investigated the effect of melatonin on autophagy in an animal model of liver fibrosis and the hepatic stellate cell (HSC)-T6 cell line.
The model was established in rats through carbon tetrachloride treatment, and melatonin was administered at three doses (2.5, 5.0, and 10.0 mg/kg). Haematoxylin and eosin staining and Van Gieson's staining were performed to examine the pathological changes of liver. The expression of alpha-smooth muscle actin (α-SMA) and Beclin1 in liver tissues was detected by immunohistochemical staining. The protein levels of α-SMA, Beclin1 and LC3 in the animal model were detected by Western blot analysis, and gene levels of Beclin1 and LC3 were detected by quantitative real-time PCR (qRT-PCR) in the animal model. HSC-T6 cells were activated by platelet-derived growth factor-BB (PDGF-BB). The expression of α-SMA, Beclin1 and collagen I was detected by Western blot analysis, and the gene expression of Beclin1 and LC3 was detected by qRT-PCR.
Melatonin reduced the expression of α-SMA, Beclin1 and LC3 in liver tissues. In addition, melatonin inhibited the activation of HSC-T6 cells and the expression of α-SMA, Beclin1 and LC3 in these cells. These results revealed that melatonin could inhibit autophagy and HSC activation.
Melatonin might ameliorate liver fibrosis by regulating autophagy, suggesting that melatonin is a potential therapeutic agent for liver fibrosis.
有报道称褪黑素可抑制炎症反应，减轻肝纤维化，但褪黑素对肝纤维化自噬的影响尚未得到研究。本研究旨在探讨褪黑素对肝纤维化动物模型及肝星状细胞（HSC）-T6 细胞系自噬的影响。
采用四氯化碳处理大鼠建立模型，并给予褪黑素（2.5、5.0 和 10.0mg/kg）三个剂量进行治疗。采用苏木精-伊红（HE）染色和 Van Gieson 染色观察肝脏的病理变化。免疫组化染色检测肝组织中α-平滑肌肌动蛋白（α-SMA）和 Beclin1 的表达。Western blot 分析检测动物模型中α-SMA、Beclin1 和 LC3 的蛋白水平，实时荧光定量 PCR（qRT-PCR）检测动物模型中 Beclin1 和 LC3 的基因水平。血小板衍生生长因子-BB（PDGF-BB）激活 HSC-T6 细胞，Western blot 分析检测α-SMA、Beclin1 和胶原 I 的表达，qRT-PCR 检测 Beclin1 和 LC3 的基因表达。
褪黑素降低了肝组织中α-SMA、Beclin1 和 LC3 的表达。此外，褪黑素抑制了 HSC-T6 细胞的激活及其细胞中α-SMA、Beclin1 和 LC3 的表达。这些结果表明，褪黑素可抑制自噬和 HSC 的激活。
褪黑素可能通过调节自噬改善肝纤维化，提示褪黑素可能是肝纤维化的一种潜在治疗药物。
