Chang Hong, Lu Zuneng
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue. 2016 Mar;28(3):272-6.
To investigate the clinical significance of serum microRNA-151a-3p (miR-151a-3p) expression in peripheral blood of patients with acute cerebral infarction (ACI), and to analyze the correlation between miR-151a-3p and related inflammatory factors, in order to obtain new evidence and ideas in the diagnosis and treatment of ACI.
A retrospective analysis was conducted. The clinical data of patients with ACI admitted to Department of Neurology of People's Hospital of Wuhan University from April to July in 2004 were enrolled. 114 ACI patients with first onset and duration of 2-14 days served as the research objects, and in the same period 58 healthy persons with matched age, and gender served as healthy control group. The risk factors of cerebral infarction in ACI patients and levels of serum miR-151a-3p, interleukins (IL-6, IL-8), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) in all the subjects were completely recorded. The correlation between serum miR-151a-3p and the area and type of cerebral infarction, the causes of infarction as well as the inflammatory cytokines was analyzed. The correlation of 10-year survival rate of patients with different expression levels of miR-151a-3p in patients with ACI was analyzed.
A total of 114 patients with ACI were enrolled, with 59 male, 55 female, and age ranged 48-63 years with a mean of (55.0±6.7) years. Large infarction was found in 25 cases, middle sized infarction in 26 cases, small infarction in 53 cases, and lacunar infarction in 10 cases. According to the modified Trial of Org 10172 in acute stroke treatment (TOAST), the patients were classified as thrombotic cerebral infarction (AT) 92 cases, embolism (CE) from cardiac origin 10 cases, and small arterial occlusive cerebral infarction (SAD) 12 cases. After eliminating the influence of cerebral infarction risk factors on the expression level of miRNAs, and compared with that of healthy control group, the level of serum miR-151a-3p expression was significantly increased in ACI group (2-ΔΔCt: 2.28±1.85 vs. 1.27±0.98, P < 0.01); the levels of serum miR-151a-3p in large, middle, small, lacunar infarction groups were markedly up-regulated (2-ΔΔCt: 1.78±1.02, 1.92±1.11, 2.22±1.54, 2.61±1.82 vs. 1.27±0.98, all P < 0.05) with no significant difference among different infarction groups. The serum miR-151a-3p expression in AT and CE groups was significantly higher than that of the healthy control group (2-ΔΔCt: 2.01±1.45, 1.99±0.89 vs. 1.27±0.98, both P < 0.05), but no significant difference was found between SAD group and healthy control group (2-ΔΔCt: 1.72±0.30 vs. 1.27±0.98, P > 0.05). The levels of serum IL-6, IL-8, CRP and TNF-α in ACI group were all higher than those of healthy control group [IL-6 (ng/L): 45.21±14.33 vs. 39.70±13.15, IL-8 (μg/L): 29.12±14.92 vs. 22.50±10.12, CRP (mg/L): 6.61±3.02 vs. 5.40±2.75, TNF-α (ng/L): 65.20±16.14 vs. 55.70±14.35, all P < 0.05]. In addition, higher expression of serum pro-inflammatory mediators IL-6, IL-8, CRP and TNF-α were positively correlated with miR-151a-3p (R2 value were 0.092, 0.055, 0.034, 0.036, all P < 0.05). Ten-year survival rate was higher in patients with low expression of miR-151a-3p [with 1.27±1.98 as the boundary, 48.57% (17/35) vs. 34.18% (27/79), log-rank = 3.411, P = 0.045].
Up-regulated serum miR-151a-3p may be involved in the pathophysiology of ACI. Therefore, miR-151a-3p may be used as a reference to predict the severity of neurological deficit in clinic.
探讨急性脑梗死(ACI)患者外周血血清微小RNA-151a-3p(miR-151a-3p)表达的临床意义,分析miR-151a-3p与相关炎症因子的相关性,以期为ACI的诊治提供新的依据和思路。
采用回顾性分析。选取武汉大学人民医院神经内科2004年4月至7月收治的ACI患者的临床资料。114例首发且病程为2~14天的ACI患者作为研究对象,同期选取58例年龄、性别相匹配的健康人作为健康对照组。完整记录ACI患者脑梗死的危险因素及所有研究对象血清miR-151a-3p、白细胞介素(IL-6、IL-8)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)水平。分析血清miR-151a-3p与脑梗死面积、类型、梗死原因以及炎症细胞因子之间的相关性。分析不同miR-151a-3p表达水平的ACI患者10年生存率的相关性。
共纳入114例ACI患者,其中男性59例,女性55例,年龄48~63岁,平均(55.0±6.7)岁。大面积梗死25例中,等面积梗死26例,小面积梗死53例,腔隙性梗死10例。根据改良急性卒中治疗Org 10172试验(TOAST),患者分为血栓性脑梗死(AT)92例、心源性栓塞(CE)10例、小动脉闭塞性脑梗死(SAD)12例。排除脑梗死危险因素对miRNAs表达水平的影响后,与健康对照组相比,ACI组血清miR-151a-3p表达水平显著升高(2-ΔΔCt:2.28±1.85比1.27±0.98,P<0.01);大面积、等面积、小面积、腔隙性梗死组血清miR-151a-3p水平均明显上调(2-ΔΔCt:1.78±1.02、1.92±1.11、2.22±1.54、2.61±1.82比1.27±0.98,均P<0.05),不同梗死组间差异无统计学意义。AT组和CE组血清miR-151a-3p表达明显高于健康对照组(2-ΔΔCt:2.01±1.45、1.99±0.89比1.27±0.98,均P<0.05),但SAD组与健康对照组比较差异无统计学意义(2-ΔΔCt:1.72±0.30比1.27±0.98,P>0.05)。ACI组血清IL-6、IL-8、CRP和TNF-α水平均高于健康对照组[IL-6(ng/L):45.21±14.33比39.70±13.15,IL-8(μg/L):29.12±14.92比22.50±10.12,CRP(mg/L):6.61±3.02比5.40±2.75,TNF-α(ng/L):65.20±16.14比55.70±14.35,均P<0.05]。此外,血清促炎介质IL-6、IL-8、CRP和TNF-α的高表达与miR-151a-3p呈正相关(R2值分别为0.092、0.055、0.034、0.036,均P<0.05)。miR-151a-3p低表达患者的10年生存率较高[以1.27±1.98为界,48.57%(17/35)比34.18%(27/79),log-rank=3.411,P=0.045]。
血清miR-151a-3p上调可能参与了ACI的病理生理过程。因此,miR-151a-3p可能作为临床预测神经功能缺损严重程度的参考指标。