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甘丙肽通过激活 AMPK/ACC 信号通路和改变巨噬细胞炎症表型来改善小鼠的肝脏炎症和纤维化。

Galanin ameliorates liver inflammation and fibrosis in mice by activating AMPK/ACC signaling and modifying macrophage inflammatory phenotype.

机构信息

Department of Gastroenterology, Huadong Hospital Affiliated to Fudan University, Shanghai, China.

Department of Geriatrics, Huadong Hospital Affiliated to Fudan University, Shanghai, China.

出版信息

Front Immunol. 2023 Apr 26;14:1161676. doi: 10.3389/fimmu.2023.1161676. eCollection 2023.

DOI:10.3389/fimmu.2023.1161676
PMID:37180164
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10169601/
Abstract

BACKGROUND AND AIMS

Galanin is a naturally occurring peptide that plays a critical role in regulating inflammation and energy metabolism, with expression in the liver. The exact involvement of galanin in non-alcoholic fatty liver disease and related fibrosis remains controversial.

METHODS

The effects of subcutaneously administered galanin were studied in mice with non-alcoholic steatohepatitis (NASH) induced by a high-fat and high-cholesterol diet for 8 weeks, and in mice with liver fibrosis induced by CCl for 7 weeks. The underlying mechanism was also studied on murine macrophage cells (J774A.1 and RAW264.7).

RESULTS

Galanin reduced inflammation, CD68-positive cell count, MCP-1 level, and mRNA levels of inflammation-related genes in the liver of NASH mice. It also mitigated liver injury and fibrosis caused by CCl. , galanin had anti-inflammatory effects on murine macrophages, including reduced phagocytosis and intracellular reactive oxygen species (ROS). Galanin also activated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) signaling.

CONCLUSION

Galanin ameliorates liver inflammation and fibrosis in mice, potentially by modifying macrophage inflammatory phenotype and activating AMPK/ACC signaling.

摘要

背景和目的

甘丙肽是一种内源性肽,在调节炎症和能量代谢方面发挥着关键作用,在肝脏中表达。甘丙肽在非酒精性脂肪性肝病及其相关纤维化中的确切作用仍存在争议。

方法

研究了皮下给予甘丙肽对高脂高胆固醇饮食诱导的非酒精性脂肪性肝炎(NASH)8 周和 CCl 诱导的肝纤维化 7 周小鼠的影响。还在小鼠巨噬细胞(J774A.1 和 RAW264.7)上研究了其潜在机制。

结果

甘丙肽降低了 NASH 小鼠肝脏中的炎症、CD68 阳性细胞计数、MCP-1 水平和炎症相关基因的 mRNA 水平。它还减轻了 CCl 引起的肝损伤和纤维化。甘丙肽对小鼠巨噬细胞具有抗炎作用,包括减少吞噬作用和细胞内活性氧(ROS)。甘丙肽还激活了 AMP 激活的蛋白激酶(AMPK)/乙酰辅酶 A 羧化酶(ACC)信号通路。

结论

甘丙肽可改善小鼠的肝脏炎症和纤维化,可能通过改变巨噬细胞的炎症表型和激活 AMPK/ACC 信号通路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/cf69596b2b34/fimmu-14-1161676-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/bea7bbb421db/fimmu-14-1161676-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/7b428b495fc2/fimmu-14-1161676-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/34d73d64bf65/fimmu-14-1161676-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/1b10c1be10ef/fimmu-14-1161676-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/b9657047518f/fimmu-14-1161676-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/cf69596b2b34/fimmu-14-1161676-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/bea7bbb421db/fimmu-14-1161676-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/7b428b495fc2/fimmu-14-1161676-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/34d73d64bf65/fimmu-14-1161676-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/1b10c1be10ef/fimmu-14-1161676-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/b9657047518f/fimmu-14-1161676-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3f05/10169601/cf69596b2b34/fimmu-14-1161676-g006.jpg

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