Clough Geraldine F, Chipperfield Andrew J, Thanaj Marjola, Scorletti Eleonora, Calder Philip C, Byrne Christopher D
Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, United Kingdom.
Faculty of Engineering and Physical Sciences, University of Southampton, Southampton, United Kingdom.
Front Physiol. 2020 Jun 3;11:551. doi: 10.3389/fphys.2020.00551. eCollection 2020.
BACKGROUND/AIMS: Increasing evidence shows that non-alcoholic fatty liver disease (NAFLD) is associated with dysregulation of microvascular perfusion independently of established cardio-metabolic risk factors. We investigated whether hepatic manifestations of NAFLD such as liver fibrosis and liver fat are associated with microvascular hemodynamics through dysregulation of neurovascular control.
Microvascular dilator (post-occlusive reactive hyperemia) and sympathetically mediated constrictor (deep inspiratory breath-hold) responses were measured at the forearm and finger, respectively, using laser Doppler fluximetry. Non-linear complexity-based analysis was used to assess the information content and variability of the resting blood flux (BF) signals, attributable to oscillatory flow-motion activity, and over multiple sampling frequencies.
Measurements were made in 189 adults (113 men) with NAFLD, with ( = 65) and without ( = 124) type 2 diabetes mellitus (T2DM), age = 50.9 ± 11.7 years (mean ± SD). Microvascular dilator and constrictor capacity were both negatively associated with age ( = -0.178, = 0.014, and = -0.201, = 0.007, respectively) and enhanced liver fibrosis (ELF) score ( = -0.155, = 0.038 and = -0.418, < 0.0001, respectively). There was no association with measures of liver fat, obesity or T2DM. Lempel-Ziv complexity (LZC) and sample entropy (SE) of the BF signal measured at the two skin sites were associated negatively with age ( < 0.01 and < 0.001) and positively with ELF score ( < 0.05 and < 0.0001). In individuals with an ELF score ≥7.8 the influence of both neurogenic and respiratory flow-motion activity on LZC was up-rated ( < 0.0001).
Altered microvascular network functionality occurs in adults with NAFLD suggesting a mechanistic role for dysregulated neurovascular control in individuals at risk of severe liver fibrosis.
背景/目的：越来越多的证据表明，非酒精性脂肪性肝病（NAFLD）与微血管灌注失调有关，且独立于已确定的心血管代谢危险因素。我们研究了NAFLD的肝脏表现，如肝纤维化和肝脂肪，是否通过神经血管控制失调与微血管血流动力学相关。
分别使用激光多普勒血流仪在前臂和手指测量微血管扩张剂（闭塞后反应性充血）和交感神经介导的收缩剂（深吸气屏气）反应。基于非线性复杂度的分析用于评估静息血流（BF）信号的信息含量和变异性，这些信号归因于振荡血流运动活动，并涉及多个采样频率。
对189名患有NAFLD的成年人（113名男性）进行了测量，其中有（n = 65）和没有（n = 124）2型糖尿病（T2DM），年龄为50.9±11.7岁（平均值±标准差）。微血管扩张剂和收缩剂能力均与年龄呈负相关（分别为r = -0.178，P = 0.014和r = -0.201，P = 0.007）以及与增强肝纤维化（ELF）评分呈负相关（分别为r = -0.155，P = 0.038和r = -0.418，P < 0.0001）。与肝脂肪、肥胖或T2DM的测量指标无关联。在两个皮肤部位测量的BF信号的Lempel-Ziv复杂度（LZC）和样本熵（SE）与年龄呈负相关（P < 0.01和P < 0.001），与ELF评分呈正相关（P < 0.05和P < 0.0001）。在ELF评分≥7.8的个体中，神经源性和呼吸性血流运动活动对LZC的影响均增强（P < 0.0001）。
患有NAFLD的成年人存在微血管网络功能改变，提示神经血管控制失调在有严重肝纤维化风险的个体中起机制性作用。
