Liver microcirculation disturbance in nonalcoholic fatty liver disease
-
摘要: 目前非酒精性脂肪性肝病发病机制尚不完全清楚,但肝脏微循环灌注改变是疾病进展的一个重要特征,其中肝细胞脂肪蓄积是导致微血管损伤的关键。介绍了正常微循环功能及结构、神经调节,着重分析了肝病微循环变化机制继而引发的微观细胞分子水平变化及宏观影像学改变。故推测,探明肝脏微循环变化可为非酒精性脂肪性肝病的病理生物学提供新见解,优化无创诊断帮助识别高危人群及早期非酒精性脂肪性肝炎患者。Abstract: At present, the pathogenesis of nonalcoholic fatty liver disease ( NAFLD) is not completely clear, but hepatic microcirculation perfusion is an important feature of disease progression, in which lipid accumulation in hepatocytes is the key to microvascular injury. This article introduces the function, structure, and neuromodulation of normal microcirculation, with a focus on the mechanism of liver microcirculation disturbance and the changes in cellular molecules and imaging findings due to such disturbance. Therefore, clarification of liver microcirculation disturbance can provide new insights into the pathophysiology of NAFLD, and optimized noninvasive diagnostic methods may help to identify high-risk populations and patients in the early stage of nonalcoholic steatohepatitis.
-
Key words:
- nonalcoholic fatty liver disease /
- microcirculation /
- review
-
[1] YOUNOSSI ZM, KOENIG AB, ABDELATIF D, et al. Global epidemiology of nonalcoholic fatty liver disease-Meta-analytic assessment of prevalence, incidence, and outcomes[J]. Hepatology, 2016, 64 (1) :73-84. [2]WONG RJ, MARIA A, RAMSEY C, et al. Nonalcoholic steatohepatitis is the second leading etiology of liver disease among adults awaiting liver transplantation in the United States[J].Gastroenterology, 2015, 148 (3) :547-555. [3]National Workshop on Fatty Liver and Alcoholic Liver Disease, Chinese Society of Hepatology, Chinese Medical Association;Fatty Liver Expert Committee, Chinese Medical Doctor Association. Guidelines of prevention and treatment for nonalcoholic fatty liver disease:A 2018 update[J]. J Clin Hepatol, 2018, 34 (5) :947-957. (in Chinese) 中华医学会肝病学分会脂肪肝和酒精性肝病学组, 中国医师协会脂肪性肝病专家委员会.非酒精性脂肪性肝病防治指南 (2018年更新版) [J].临床肝胆病杂志, 2018, 34 (5) :947-957. [4]SAFIRI S, KHAZAEI S, MANSORI K, et al. Comments on increased risk of mortality by fibrosis stage in nonalcoholic fatty liver disease:Systematic review and meta-analysis[J]. Hepatology, 2017, 65 (5) :1358-1359. [5]BAFFY G. Origins of portal hypertension in nonalcoholic fatty liver disease[J]. Dig Dis Sci, 2018, 63 (3) :1-14. [6]LI B, SU Q. Relationship between advanced glycation endproducts and its receptor in nonalcoholic fatty liver diseases[J]. Int J Endocrinol Metab, 2017, 37 (3) :192-194. (in Chinese) 李博, 苏青.晚期糖基化终末产物及其受体与非酒精性脂肪性肝病的关系[J].国际内分泌代谢杂志, 2017, 37 (3) :192-194. [7]LIU QB, LI HW. Advanced glycation end products and atherosclerosis[J]. Chin J Cardiovasc Med, 2018, 23 (1) :87-91. (in Chinese) 刘青波, 李虹伟.晚期糖基化终末产物与动脉粥样硬化[J].中国心血管杂志, 2018, 23 (1) :87-91. [8]PAIZIS G, COOPER ME, SCHEMBRI JM, et al. Up-regulation of components of the renin-angiotensin system in the bile duct-ligated rat liver[J]. Gastroenterology, 2002, 123 (5) :1667-1676. [9]GARDEMANN A, PUSCHEL GP, JUNGERMANN K. Nervous control of liver metabolism and hemodynamics[M]//EJB Reviews. Springer Berlin Heidelberg, 1993:399-411. [10]AMENTA F, CAVALLOTTI C, FERRANRE F, et al. Cholinergic nerves in the human liver[J]. Histochem J, 1981, 13 (3) :419-424. [11]HYOGO H, YAMAGISHI S, IWAMOTO K, et al. Elevated levels of serum advanced glycation end products in patients with non-alcoholic steatohepatitis[J]. J Gastroenterol Hepatol, 2007, 22 (7) :1112-1119. [12]SAYEJ WN, KNIGHT LII PR, GUO WA, et al. Advanced glycation end products induce obesity and hepatosteatosis in CD-1 wildtype mice[J]. Biomed Res Int, 2016, 2016 (1) :7867852. [13]YANG YL, ZHENG LY, GU WM, et al. Effect of total glucosides of paeony regulate HMGB1, RAGE pathway on nonalcoholic fatty liver disease in rats[J]. Chin J Clin Pharmacol Ther, 2017, 22 (6) :611-616. (in Chinese) 杨以琳, 郑琳颖, 古伟明, 等.白芍总苷对非酒精性脂肪性肝病大鼠HMGB1、RAGE通路的调控作用[J].中国临床药理学与治疗学, 2017, 22 (6) :611-616. [14]PEREIRA ENGDS, SILVARES RR, FLORES EEI, et al. Hepatic microvascular dysfunction and increased advanced glycation end products are components of non-alcoholic fatty liver disease[J]. PLo S One, 2017, 12 (6) :e0179654. [15]HORIUCHI S. The liver is the main site for metabolism of circulating advanced glycation end products[J]. J Hepatol, 2002, 36 (1) :123-125. [16]PALMA-DURAN SA, KONTOGIANNI MD, VLASSOPOULOS A, et al. Serum levels of advanced glycation end-products (AGEs) and the decoy soluble receptor for AGEs (sRAGE) can discriminate non-alcoholic fatty liver disease in age-, sex-and BMI-matched normo-glycemic adults[J]. Metabolism, 2018, 83:120-127. [17]McCUSKEY RS, ITO Y, ROBERTSON GR, et al. Hepatic microvascular dysfunction during evolution of dietary steatohepatitis in mice[J]. Hepatology, 2004, 40 (2) :386-393. [18]FUJII M, SHIBAZAKI Y, WAKAMATSU K, et al. A murine model for non-alcoholic steatohepatitis showing evidence of association between diabetes and hepatocellular carcinoma[J]. Med Mol Morphol, 2013, 46 (3) :141-152. [19]LIEBIG M, HASSANZADA A, KMMERLING M, et al. Microcirculatory disturbances and cellular changes during progression of hepatic steatosis to liver tumors[J]. Exp Biol Med (Maywood) , 2018, 243 (1) :1-12. [20]YU ZY. How to deal with fatty liver donor in liver transplantation[D]. Hangzhou:Zhejiang University, 2015. (in Chinese) 俞志勇.脂肪肝供肝肝移植的回顾性研究[D].杭州:浙江大学, 2015. [21]MIYAO M, KOTANI H, ISHIDA T, et al. Pivotal role of liver sinusoidal endothelial cells in NAFLD/NASH progression[J].Lab Invest, 2015, 95 (10) :1130-1144. [22]MATSUKUMA S, TAKEO H, UTSUMI Y, et al. In hepatic venous outflow obstruction, alcoholic liver disease, and nonalcoholic fatty liver disease, centrilobular scars, CD34+vessels, and keratin 7+hepatocytes are in close proximity[J]. Virchows Archiv, 2017, 470 (4) :411-420. [23]ZHAO YH, DUAN SP. Study on the relationship between blood lipid and hemorheology in patients with fatty liver[J]. Hebei Med, 2013, 19 (2) :304-306. (in Chinese) 赵艳会, 段淑平.脂肪肝患者血脂与血液流变学关系的研究[J].河北医学, 2013, 19 (2) :304-306. [24]REEVES HL, FRIEDMAN SL. Activation of hepatic stellate cells—a key issue in liver fibrosis[J]. Front Biosci, 2002, 7 (1-3) :d808. [25]POISSON J, LEMOINNE S, BOULANGER C, et al. Liver sinusoidal endothelial cells:Physiology and role in liver diseases[J]. J Hepatol, 2016, 66 (1) :212-227. [26]DECARIS ML, LI KW, EMSON CL, et al. Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood[J]. Hepatology, 2017, 65 (1) :78-88. [27]NIU GH, GAO LW, QIAN JF, et al. Changes of platelet activation, hemorheology and nailfold microcirculation in patients with primary hepatocellular carcinoma[J]. Exp Lab Med, 2018, 36 (2) :234-236. (in Chinese) 牛国浩, 高立伟, 钱俊甫, 等.原发性肝癌患者血小板活化、血流变与甲襞微循环的变化研究[J].实验与检验医学, 2018, 36 (2) :234-236. [28]WANG Q, YANG L. Research progress in quantitative evaluation by imaging biomarker of liver microenvironment[J]. J Med Imaging, 2017, 27 (2) :333-336. (in Chinese) 王倩, 杨立.影像生物学标记定量评价肝脏微环境的研究进展[J].医学影像学杂志, 2017, 27 (2) :333-336. [29]STURESSON C, MILSTEIN DM, POST IC, et al. Laser speckle contrast imaging for assessment of liver microcirculation[J]. Microvasc Res, 2013, 87:34-40. [30]NASR P, HILLIGES A, THORELIUS L, et al. Contrast-enhanced ultrasonography could be a non-invasive method for differentiating none or mild from severe fibrosis in patients with biopsy proven non-alcoholic fatty liver disease[J]. Scand J Gastroenterol, 2016, 51 (9) :1126-1132. [31]ZHANG Y, JIA L. Double-blind study of aspirin in treating non-alcoholic fatty liver disease[J]. J Qiqihar Med Coll, 2015, 36 (31) :4687-4689. (in Chinese) 张影, 贾丽.阿司匹林治疗非酒精性脂肪肝的双盲研究[J].齐齐哈尔医学院学报, 2015, 36 (31) :4687-4689.
本文二维码
计量
- 文章访问数: 1107
- HTML全文浏览量: 27
- PDF下载量: 302
- 被引次数: 0