背景:在急性心肌梗死和肺栓塞患者中已证实肠道菌群失调会导致循环中肠屏障通透性增加和脂多糖(LPS)易位。
目的:我们研究了急性缺血性中风(AIS)中循环LPS浓度的变化及其后果,包括预后。
方法:我们研究了98例AIS患者,年龄74±12岁,包括74例(75.5%)溶栓患者。我们测定了血清LPS和zonulin,肠道通透性的标志,随着蛋白质羰基化(PC),纤维蛋白凝块特性,和入院时的凝血酶生成,24小时零3个月.使用NIH卒中量表(NIHSS)评估卒中严重程度。使用改良的Rankin量表(mRS)评估卒中功能结局,并在3个月时评估卒中相关死亡率。
结果:入院时血清LPS和zonulin与症状发作时间相关(r=0.57,p<0.0001和r=0.40,p<0.0001)。基线LPS与PC相关(r=0.51,p<0.0001),但与凝血和纤溶标志物无关。溶栓患者的LPS水平在24小时时升高(p<0.001),并与NIHSS评分(r=0.31,p=0.002)和PC(r=0.32,p=0.0057)相关。在24小时测量的LPS和连体蛋白水平都增加了具有不利的mRS的几率(OR=1.22,95CI,1.04-1.42和2.36,95CI,每单位1.24-4.49)。LPS升高,但不是zonulin,与卒中相关死亡率相关(OR=1.26,95CI,每单位1.02~1.55).
结论:在AIS患者中,肠通透性主要是由自症状发作以来的时间增加引起的。我们的发现表明,溶栓后LPS有进一步上升的趋势,会对神经功能结局和3个月死亡率产生不利影响。
BACKGROUND: Gut dysbiosis leading to increased intestinal barrier permeability and translocation of lipopolysaccharide (LPS) in the circulation has been demonstrated in patients with acute myocardial infarction and pulmonary embolism.
OBJECTIVE: We investigated changes in circulating LPS concentrations in acute ischemic stroke (AIS) and their consequences, including prognosis.
METHODS: We studied 98 AIS patients, aged 74±12 years, including 74 (75.5%) thrombolysed individuals. We determined serum LPS and
zonulin, a marker of gut permeability, along with protein carbonylation (PC), fibrin clot properties, and thrombin generation on admission, at 24 hours and 3 months. Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke functional outcome using modified Rankin Scale (mRS) and stroke-related mortality were evaluated at 3 months.
RESULTS: Serum LPS and
zonulin on admission were associated with time since symptom onset (r=0.57, p<0.0001 and r=0.40, p<0.0001). Baseline LPS correlated with PC (r=0.51, p<0.0001) but not with coagulation and fibrinolysis markers. LPS levels increased at 24 hours in thrombolysed patients (p<0.001) and correlated with the NIHSS score (r=0.31, p=0.002) and PC (r=0.32, p=0.0057). Both LPS and
zonulin levels measured at 24 hours increased the odds of having unfavorable mRS (OR=1.22, 95%CI, 1.04-1.42 and 2.36, 95%CI, 1.24-4.49 per unit). Elevated LPS, but not
zonulin, was associated with stroke-related mortality (OR=1.26, 95%CI, 1.02-1.55 per unit).
CONCLUSIONS: In AIS patients intestinal permeability is mainly driven by increasing time since the symptom onset. Our findings suggest that LPS with a trend toward its further rise following thrombolysis adversely affect neurological functional outcomes and 3-month mortality.