巨噬细胞在非酒精性脂肪性肝病中的作用

罗雨欣; 郭金波; 张晓岚

doi:10.3969/j.issn.1001-5256.2020.03.046

巨噬细胞在非酒精性脂肪性肝病中的作用

DOI: 10.3969/j.issn.1001-5256.2020.03.046

河北医科大学第二医院消化内科

基金项目:

国家自然科学基金资助项目(81900522)；

详细信息

中图分类号: R575.5
计量
- 文章访问数: 837
- HTML全文浏览量: 33
- PDF下载量: 233
- 被引次数: 0
出版历程
- 收稿日期: 2019-10-17
- 出版日期: 2020-03-20

Research advances in the role of macrophages in nonalcoholic fatty liver disease

Department of Gastroenterology,The Second Hospital of Hebei Medical University

Research funding:

摘要

摘要: 随着生活水平的提高,非酒精性脂肪性肝病(NAFLD)发病率逐年升高并且趋于年轻化,但其具体发病机制尚未明确。巨噬细胞作为参与NAFLD发病的重要细胞之一,一直广受关注。针对肝脏巨噬细胞的来源及分类、巨噬细胞在NAFLD肝脏炎症中的作用和其活化的机制、靶向巨噬细胞药物进行阐述,旨在为临床治疗NAFLD提供参考。
- 非酒精性脂肪性肝病 /
- 巨噬细胞 /
- 治疗学
Abstract: With the improvement of living standard,the incidence rate of nonalcoholic fatty liver disease( NAFLD) is gradually increasing year by year and its age of onset tends to become younger,but its pathogenesis remains unclear. Macrophages are important cells involved in the pathogenesis of NAFLD and have attracted great attention. This article elaborates on the origin and classification of liver macrophages,the role of macrophages in liver inflammation and related activation mechanism,and the drugs targeting macrophages,in order to provide a reference for the clinical treatment of NAFLD.
- non-alcoholic fatty liver disease /
- macrophages /
- therapeutics

HTML全文

参考文献(34)

[1] YOUNOSSI ZM,MARCHESINI G,PINTO-CORTEZ H,et al.Epidemiology of nonalcoholic fatty liver disease and nonalcoholic steatohepatitis:Implications for liver transplantation[J].Transplantation,2019,103(1):22-27.

[2] YOUNOSSI Z,TACKE F,ARRESE M,et al. Global perspectives on non-alcoholic fatty liver disease and non-alcoholic steatohepatitis[J]. Hepatology,2019,69(6):2672-2682.

[3] ZHU JZ,ZHOU QY,WANG YM,et al. Prevalence of fatty liver disease and the economy in China:A systematic review[J].World J Gastroenterol,2015,21(18):5695-5706.

[4] BIJNEN M,JOSEFS T,CUIJPERS I,et al. Adipose tissue macrophages induce hepatic neutrophil recruitment and macrophage accumulation in mile[J]. Gut,2018,67(7):1317-1327.

[5] MRIDHA AR,WREE A,AAB R,et al. NLRP3 inflammasome blockade reduces liver inflammation and fibrosis in experimental NASH in mice[J]. J Hepatol,2017,66(5):1037-1046.

[6] IMAJO K,FUJITA K,YONEDA M,et al. Hyperresponsivity to low-dose endotoxin during progression to nonalcoholic steatohepatitis is regulated by leptin-mediated signaling[J].Cell Metab,2012,16(1):44-54.

[7] YAMADA S,KAMADA N,AMIYA T,et al. Gut microbiotamediated generation of saturated fatty acids elicits inflammation in the liver in murine high-fat diet-induced steatohepatitis[J]. BMC Gastroenterol,2017,17(1):136.

[8] GADD VL,SKOIEN R,POWELL EE,et al. The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease[J]. Hepatology,2014,59(4):1393-1405.

[9] PARK JW,JEONG G,KIM SJ,et al. Predictors reflecting the pathological severity of non-alcoholic fatty liver disease:Comprehensive study of clinical and immunohistochemical findings in younger Asian patients[J]. J Gastroenterol Hepatol,2007,22(4):491-497.

[10] TOSELLO-TRAMPONT AC,LANDES SG,NGUYEN V,et al.Kuppfer cells trigger nonalcoholic steatohepatitis development in diet-induced mouse model through tumor necrosis factor-αproduction[J]. J Biol Chem,2012,287(48):40161-40172.

[11] SONG M,SCHUSCHKE DA,ZHOU Z,et al. Kupffer cell depletion protects against the steatosis,but not the liver damage,induced by marginal-copper,high-fructose diet in male rats[J]. Am J Physiol Gastrointest Liver Physiol,2015,308(11):g934-g945.

[12] RENSEN SS,SLAATS Y,NIJHUIS J,et al. Increased hepatic myeloperoxidase activity in obese subjects with nonalcoholic steatohepatitis[J]. Am J Pathol,2009,175(4):1473-1482.

[13] JINDAL A,BRUZZI S,SUTTI S,et al. Fat-laden macrophages modulate lobular inflammation in nonalcoholic steatohepatitis(NASH)[J]. Exp Mol Pathol,2015,99(1):155-162.

[14] STANTON MC,CHEN SC,JACKSON JV,et al. Inflammatory signals shift from adipose to liver during high fat feeding and influence the development of steatohepatitis in mice[J]. J Inflamm(Lond),2011,8:8.

[15] du PLESSIS J,van PELT J,KORF H,et al. Association of adipose tissue inflammation with histological severity of nonalcoholic fatty liver disease[J]. Gastroenterology,2015,149(3):635-648,e14.

[16] WREE A,EGUCHI A,MCGEOUGH MD,et al. NLRP3 inflammasome activation results in hepatocyte pyroptosis,liver inflammation,and fibrosis in mice[J]. Hepatology,2014,59(3):898-910.

[17] GONG Z,ZHOU J,ZHAO S,et al. Chenodeoxycholic acid activates NLRP3 inflammasome and contributes to cholestatic liver fibrosis[J]. Oncotarget,2016,7(51):83951-83963.

[18] BÄCKHED F,DING H,WANG T,et al. The gut microbiota as an environmental factor that regulates fat storage[J]. Proc Natl Acad Sci U S A,2004,101(44):15718-15723.

[19] YE JZ,LI YT,WU WR,et al. Dynamic alterations in the gut microbiota and metabolome during the development of methionine-choline-defcient diet-induced nonalcoholic steatohepatitis[J]. World J Gastroenterol,2018,24(23):2468-2481.

[20] ROBERT O,BOUJEDIDI H,BIGORGNE A,et al. Decreased expression of the glucocorticoid receptor-GILZ pathway in Kupffer cells promotes liver inflammation in obese mice[J]. J Hepatol,2016,64(4):916-924.

[21] SVENDSEN P,GRAVERSEN JH,ETZERODT A,et al. Antibody-directed glucocorticoid targeting to CD163 in M2-type macrophages attenuates fructose-induced liver inflammatory changes[J]. Mol Ther Methods Clin Dev,2017,4:50-61.

[22] LEFEBVRE E,MOYLE G,RESHEF R,et al. Antifibrotic effects of the dual CCR2/CCR5 antagonist cenicriviroc in animal models of liver and kidney fibrosis[J]. PLo S One,2016,11(6):e0158156.

[23] KRENKEL O,PUENGEL T,GOVAERE O,et al. Therapeutic inhibition of inflammatory monocyte recruitment reduces steatohepatitis and liver fibrosis[J]. Hepatology,2018,67(4):1270-1283.

[24] FRIEDMAN SL,RATZIU V,HARRISON SA,et al. A randomized,placebo-controlled trial of cenicriviroc for treatment of nonalcoholic steatohepatitis with fibrosis[J]. Hepatology,2018,67(5):1754-1767.

[25] IACOBINI C,MENINI S,RICCI C,et al. Galectin-3 ablation protects mice from diet-induced NASH:A major scavenging role for galectin-3 in liver[J]. J Hepatol,2011,54(5):975-983.

[26] NOMOTO K,NISHIDA T,NAKANISHI Y,et al. Deficiency in galectin-3 promotes hepatic injury in CDAA diet-induced nonalcoholic fatty liver disease[J]. Sci World J,2012,2012:959824.

[27] JEFTIC I,JOVICIC N,PANTIC J,et al. Galectin-3 ablation enhances liver steatosis,but attenuates inflammation and IL-33-dependent fibrosis in obesogenic mouse model of nonalcoholic steatohepatitis[J]. Mol Med,2015,21:453-465.

[28] TRRABER PG,ZOMER E. Therapy of experimental NASH and fibrosis with galectin inhibitors[J]. PLo S One,2013,8(12):e83481.

[29] HARRISON SA,MARRI SR,CHALASANI N,et al. Randomised clinical study:GR-MD-02,a galectin-3 inhibitor,vs.placebo in patients having non-alcoholic steatohepatitis with advanced fibrosis[J]. Aliment Pharmacol Ther,2016,44(11-12):1183-1198.

[30] YAO J,ZHOU CS,MA X,et al. FXR agonist GW4064 alleviates endotoxin-induced hepatic inflammation by repressing macrophage activation[J]. World J Gastroenterol,2014,20(39):14430-14441.

[31] NEUSCHWANDER-TETRI BA,LOOMBA R,SANYAL AJ,et al.Farnesoid X nuclear receptor ligand obeticholic acid for non-cirrhotic,non-alcoholic steatohepatitis(FLINT):A multicentre,randomised,placebo-controlled trial[J]. Lancet,2015,385(9972):956-965.

[32] YAMAMOTO T,NAKADE Y,YAMAUCHI T,et al. Glucagonlike peptide-1 analogue prevents nonalcoholic steatohepatitis in non-obese mice[J]. World J Gastroenterol,2016,22(8):2512-2523.

[33] ARMSTRONG MJ,GAUNT P,AITHAL GP,et al. Liraglutide safety and efficacy in patients with non-alcoholic steatohepatitis(LEAN):A multicentre,double-blind,randomised,placebo-controlled phase 2 study[J]. Lancet,2016,387(10019):679-690.

[34] ALASFOOR S,ROHM TV,BOSCH AJT,et al. Imatinib reduces non-alcoholic fatty liver disease in obese mice by targeting inflammatory and lipogenic pathways in macrophages and liver[J]. Sci Rep,2018,8(1):15331.

施引文献

资源附件(0)

访问统计