脑梗死继发癫痫患者血清miR-146a表达与脑电图严重程度及炎性因子水平的关系
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摘要
目的检测miR-146a在脑梗死继发癫痫患者血清中的表达,探究其与患者脑电图及炎性因子水平的关系。方法选取2016年6月至2018年5月收治的脑梗死患者123例,按照是否继发癫痫分为脑梗死继发癫痫组(67例)和单一脑梗死组(56例),招募同期健康体检者60例作为对照组。采集空腹静脉血,荧光实时定量PCR(qRT-PCR)检测血清miR-146a水平,同时对所有患者行脑电图检查,酶联免疫吸附(ELISA)法检测患者血清中肿瘤坏死因子-α(TNF-α)、白细胞介素-2(IL-2)、IL-10、IL-1β等炎性因子水平,Pearson检验进行相关性分析。结果与对照组比较,脑梗死继发癫痫组和单一脑梗死组患者血清miR-146a、IL-10水平均明显降低,TNF-α、IL-2、IL-1β水平明显增高,差异有统计学意义(P<0.05)。与单一脑梗死组比较,脑梗死继发癫痫组患者miR-146a、IL-10水平均明显降低,TNF-α、IL-2、IL-1β水平明显增高,差异有统计学意义(P<0.05)。与脑电图正常患者比较,脑电图轻、中、重度异常患者血清miR-146a水平显著降低(P<0.05),且miR-146a水平随着患者脑电图异常程度增加逐渐降低(P<0.05)。Pearson分析表明,血清miR-146a水平与TNF-α、IL-2、IL-1β水平负相关(r=-0.615、r=-0.542、r=-0.568,P<0.05),与IL-10水平正相关(r=0.459,P<0.05)。结论 miR-146a在脑梗死继发癫痫患者血清低表达,与血清TNF-α、IL-2、IL-1β水平负相关,与IL-10水平正相关,且随着患者脑电图严重程度增加而降低。
Objective To detect the expression levels of miR 146 a in patients with epilepsy secondary to cerebral infarction, and to explore the relationship between the electroencephalogram(ECG) and inflammatory factors levels of patients.Methods A total of 123 patients with cerebral infarction who were admitted and treated in our hospital from June 2016 to May 2018 were divided into epilepsy secondary to cerebral infarction group(n=67) and simple cerebral infarction group(n=56), at the same time, the other 60 healthy subjects who underwent physical examination were enrolled as control group.The fasting venous blood specimens were collected,and the serum levels of miR 146 a were detected by fluorescence real time quantitative PCR(qRT PCR),meanwhile, electroencephalogram examination was performed in all the patients.Moreover the serum levels of tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), IL-10, IL-1β were detected by enzyme linked immunosorbent assay(ELISA), the correlation analysis was conducted by Pearson test.Results As compared with those in control group, the serum levels of miR 146 a and IL-10 in epilepsy secondary to cerebral infarction group and simple cerebral infarction group were significantly decreased, however the serum levels of TNF-α, IL-2 and IL-1β in both groups were significantly increased(P<0.05). As compared with those in simple cerebral infarction group, the serum levels of miR 146 a and IL-10 in epilepsy secondary to cerebral infarction group were significantly decreased, however the serum levels of TNF-α, IL-2 and IL-1β were significantly increased(P<0.05). As compared with those in patients with normal ECG,the serum levels of miR-146 a were significantly decreased in patients with little and middle degree abnormal ECG,moreover, with the increase of abnormal ECG degree, the serum levels of miR 146 a were significantly decreased(P<0.05). Pearson analysis showed that serum levels of miR 146 a were negatively correlated with the levels of TNF-α, IL-2 and IL-1β(r=-0.615, r=-0.542, r=-0.568,respectively,P<0.05), however,which were positively correlated with the levels of IL-10(r=0.459,P<0.05).Conclusion The serum levels of MiR 146 a are decreased in patients with epilepsy secondary to cerebral infarction, which are negatively related with the levels of serum TNF-α, IL-2 and IL-1β, and are positively related with the levels of IL-10, moreover, with the increase of abnormal ECG degree,which are gradually decreased.
Objective To detect the expression levels of miR 146 a in patients with epilepsy secondary to cerebral infarction, and to explore the relationship between the electroencephalogram(ECG) and inflammatory factors levels of patients.Methods A total of 123 patients with cerebral infarction who were admitted and treated in our hospital from June 2016 to May 2018 were divided into epilepsy secondary to cerebral infarction group(n=67) and simple cerebral infarction group(n=56), at the same time, the other 60 healthy subjects who underwent physical examination were enrolled as control group.The fasting venous blood specimens were collected,and the serum levels of miR 146 a were detected by fluorescence real time quantitative PCR(qRT PCR),meanwhile, electroencephalogram examination was performed in all the patients.Moreover the serum levels of tumor necrosis factor-α(TNF-α), interleukin-2(IL-2), IL-10, IL-1β were detected by enzyme linked immunosorbent assay(ELISA), the correlation analysis was conducted by Pearson test.Results As compared with those in control group, the serum levels of miR 146 a and IL-10 in epilepsy secondary to cerebral infarction group and simple cerebral infarction group were significantly decreased, however the serum levels of TNF-α, IL-2 and IL-1β in both groups were significantly increased(P<0.05). As compared with those in simple cerebral infarction group, the serum levels of miR 146 a and IL-10 in epilepsy secondary to cerebral infarction group were significantly decreased, however the serum levels of TNF-α, IL-2 and IL-1β were significantly increased(P<0.05). As compared with those in patients with normal ECG,the serum levels of miR-146 a were significantly decreased in patients with little and middle degree abnormal ECG,moreover, with the increase of abnormal ECG degree, the serum levels of miR 146 a were significantly decreased(P<0.05). Pearson analysis showed that serum levels of miR 146 a were negatively correlated with the levels of TNF-α, IL-2 and IL-1β(r=-0.615, r=-0.542, r=-0.568,respectively,P<0.05), however,which were positively correlated with the levels of IL-10(r=0.459,P<0.05).Conclusion The serum levels of MiR 146 a are decreased in patients with epilepsy secondary to cerebral infarction, which are negatively related with the levels of serum TNF-α, IL-2 and IL-1β, and are positively related with the levels of IL-10, moreover, with the increase of abnormal ECG degree,which are gradually decreased.
引文
1 陈夏东,赵霁,夏子锐,等.矢状窦、大脑镰旁脑膜瘤手术与继发性癫痫的控制及防治.国际神经病学神经外科学杂志,2017,44:151-154.
2 邢孔鸯,黄绮娟,林丽卿,等.脑梗死继发癫痫的临床研究.中风与神经疾病,2015,32:926-928.
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5 郭育英,廖海燕,谢彩云,等.老年脑卒中患者癫痫发作的临床特点、脑电图表现及其危险因素分析.国际神经病学神经外科学杂志,2017,44:507-511.
6 刘首峰,巫嘉陵.脑梗死后癫痫的发病机制研究进展.临床神经病学杂志,2016,29:223-224.
7 徐菲,金平,王玉.脑卒中后癫痫发作的相关危险因素分析.中华疾病控制杂志,2017,21:179-182.
8 Meissner L,Gallozzi M,Balbi M,et al.Temporal profile of microRNA expression in contused cortex following traumatic brain injury in mice.J Neurotrauma,2015,33:713-720.
9 Kaalund SS,Ven MT,Bak M,et al.Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance.Epilepsia,2015,55:2017-2027.
10 Jiang Y,Li L,Tan X,et al.miR-210 mediates vagus nerve stimulation-induced antioxidant stress and anti-apoptosis reactions following cerebral ischemia/reperfusion injury in rats.J Neurochem,2015,134:173-181.
11 An N,Zhao W,Liu Y,et al.Elevated serum miR-106b and miR-146a in patients with focal and generalized epilepsy.Epilepsy Res,2016,127:311-316.
12 Wang L,Chopp M,Szalad A,et al.The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy.Neuroscience,2014,259:155-163.
13 Yousefzadeh N,Alipour MR,Soufi FG.Deregulation of NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.J Physiol Biochem,2015,71:51-58.
14 郑艳,陈岚,余倩.癫痫患者血清白细胞介素-1β及肿瘤坏死因子-α表达及其与脑电图的关系.中国老年学杂志,2017,37:1217-1219.
15 曾玮.急性脑梗死后继发癫痫患者的视频脑电图特点分析.内科,2016,11:927-928.
16 Vezzani A,Fujinami RS,White HS,et al.Infections,inflammation and epilepsy.Acta Neuropathol,2016,131:211-234.
17 Fregnan F,Muratori L,Simes AR,et al.Role of inflammatory cytokines in peripheral nerve injury.Neural Regen Res,2012,7:2259-2266.
18 Patel DC,Wallis G,Dahle EJ,et al.Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.Eneuro,2017,4:105-117.
19 Diamond ML,Ritter AC,Failla MD,et al.IL-1β associations with posttraumatic epilepsy development:A genetics and biomarker cohort study.Epilepsia,2015,56:991-1001.
20 Li Q,Tian Y,Wang ZF,et al.Involvement of the spinal NALP1 inflammasome in neuropathic pain and aspirin-triggered-15-epi-lipoxin A4 induced analgesia.Neuroscience,2013,254:230-240.
2 邢孔鸯,黄绮娟,林丽卿,等.脑梗死继发癫痫的临床研究.中风与神经疾病,2015,32:926-928.
3 Maxeiner HG,Schneider EM,Kurfiss ST,et al.Cerebrospinal fluid and serum cytokine profiling to detect immune control of infectious and inflammatory neurological and psychiatric diseases.Cytokine,2014,69:62-67.
4 Henshall DC.MicroRNA and epilepsy:Profiling,functions and potential clinical applications.Curr Opin Neurol,2014,27:199-205.
5 郭育英,廖海燕,谢彩云,等.老年脑卒中患者癫痫发作的临床特点、脑电图表现及其危险因素分析.国际神经病学神经外科学杂志,2017,44:507-511.
6 刘首峰,巫嘉陵.脑梗死后癫痫的发病机制研究进展.临床神经病学杂志,2016,29:223-224.
7 徐菲,金平,王玉.脑卒中后癫痫发作的相关危险因素分析.中华疾病控制杂志,2017,21:179-182.
8 Meissner L,Gallozzi M,Balbi M,et al.Temporal profile of microRNA expression in contused cortex following traumatic brain injury in mice.J Neurotrauma,2015,33:713-720.
9 Kaalund SS,Ven MT,Bak M,et al.Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-convergence on axonal guidance.Epilepsia,2015,55:2017-2027.
10 Jiang Y,Li L,Tan X,et al.miR-210 mediates vagus nerve stimulation-induced antioxidant stress and anti-apoptosis reactions following cerebral ischemia/reperfusion injury in rats.J Neurochem,2015,134:173-181.
11 An N,Zhao W,Liu Y,et al.Elevated serum miR-106b and miR-146a in patients with focal and generalized epilepsy.Epilepsy Res,2016,127:311-316.
12 Wang L,Chopp M,Szalad A,et al.The role of miR-146a in dorsal root ganglia neurons of experimental diabetic peripheral neuropathy.Neuroscience,2014,259:155-163.
13 Yousefzadeh N,Alipour MR,Soufi FG.Deregulation of NF-кB-miR-146a negative feedback loop may be involved in the pathogenesis of diabetic neuropathy.J Physiol Biochem,2015,71:51-58.
14 郑艳,陈岚,余倩.癫痫患者血清白细胞介素-1β及肿瘤坏死因子-α表达及其与脑电图的关系.中国老年学杂志,2017,37:1217-1219.
15 曾玮.急性脑梗死后继发癫痫患者的视频脑电图特点分析.内科,2016,11:927-928.
16 Vezzani A,Fujinami RS,White HS,et al.Infections,inflammation and epilepsy.Acta Neuropathol,2016,131:211-234.
17 Fregnan F,Muratori L,Simes AR,et al.Role of inflammatory cytokines in peripheral nerve injury.Neural Regen Res,2012,7:2259-2266.
18 Patel DC,Wallis G,Dahle EJ,et al.Hippocampal TNFα Signaling Contributes to Seizure Generation in an Infection-Induced Mouse Model of Limbic Epilepsy.Eneuro,2017,4:105-117.
19 Diamond ML,Ritter AC,Failla MD,et al.IL-1β associations with posttraumatic epilepsy development:A genetics and biomarker cohort study.Epilepsia,2015,56:991-1001.
20 Li Q,Tian Y,Wang ZF,et al.Involvement of the spinal NALP1 inflammasome in neuropathic pain and aspirin-triggered-15-epi-lipoxin A4 induced analgesia.Neuroscience,2013,254:230-240.