龚瑜;刘宏坤;郑芝欣;顾亮亮;

• 1:南阳市中心医院

摘要(Abstract)：

目的探讨曲美他嗪辅助治疗急性脑梗死(acute cerebral infarction,ACI)患者的临床疗效、不良反应及对Th17/Treg细胞及其相关细胞因子水平的影响。方法纳入南阳市中心医院84例急性脑梗死患者为研究对象,分为对照组(n=42)和观察组(n=42)。对照组采用常规治疗,观察组在常规治疗的基础辅助曲美他嗪口服(3次/d,20mg/次),2组均治疗2周。观察2组患者治疗后的临床疗效、不良反应及Th17比例、Treg比例、Th17/Treg比值及其相关细胞因子水平。结果 2周后,观察组和对照组总有效率分别为97.62%和83.33%,与对照组相比,观察组总有效率显著升高(97.62%vs 83.33%,P=0.026)。2组患者治疗前Th17比例、Treg比例、Th17/Treg比值、血清IL-17A和TGF-β水平相比,差异均无统计学意义(P>0.05);2周后,与对照组相比,观察组Th17比例、Th17/Treg比值和血清IL-17A水平显著降低,而Treg比例及血清TGF-β水平显著升高,差异均有统计学意义(P<0.05)。2组不良反应发生率比较差异无统计学意义(P=0.724)。结论曲美他嗪辅助治疗ACI临床疗效显著,可能与改善ACI患者Th17/Treg细胞平衡有关,且不增加药物不良反应。

关键词(KeyWords)： 急性脑梗死;曲美他嗪;Th17细胞;Treg细胞;IL-17A;TGF-β;炎症因子

Abstract:

Keywords:

基金项目(Foundation): 河南省医学科技攻关计划普通项目(编号：201702127)

作者(Authors): 龚瑜;刘宏坤;郑芝欣;顾亮亮;

参考文献(References)：

• [1]PIAO J M,WU W,YANG Z X,et al.MicroRNA-381Favors Repair of Nerve Injury Through Regulation of the SDF-1/CXCR4Signaling Pathway via LRRC4in A-cute Cerebral Ischemia after Cerebral Lymphatic Blockage[J].Cell Physiol Biochem,2018,46(3):890-906.DOI:10.1159/000488821．
• [2]HANNE L,BRUNECKER P,GRITTNER U,et al.Right insular infarction and mortality after ischaemic stroke[J].Eur J Neurol,2017,24(1):67-72.DOI:10.1111/ene.13131．
• [3]ZHANG T,XIANG L.Elevated Plasma Haptoglobin Level as a Potential Marker for Poor Prognosis in Acute Cerebral Infarction[J].Eur Neurol,2018,79(3):154-160.DOI:10.1159/000487648．
• [4]ZHAO X J,LI Q X,LIU T J,et al.Predictive values of CSS and NIHSS in the prognosis of patients with acute cerebral infarction:A comparative analysis[J].Medicine(Baltimore),2018,97(39):e12419.DOI:10.1097/MD.0000000000012419．
• [5]WU X,LIU X,HUANG H,et al.Effects of major ozonated autoheamotherapy on functional recovery,ischemic brain tissue apoptosis and oxygen free radical damage in the rat model of cerebral ischemia[J].J Cell Biochem,2019,120(4):6772-6780.DOI:10.1002/jcb.27978．
• [6]CHEN L,YANG Q,DING R,et al.Carotid thickness and atherosclerotic plaque stability,serum inflammation,serum MMP-2and MMP-9were associated with acute cerebral infarction[J].Exp Ther Med,2018,16(6):5253-5257.DOI:10.3892/etm.2018.6868．
• [7]VON K R,DZIALOWSKI I.Imaging of cerebral ischemic edema and neuronal death[J].Neuroradiology,2017,59(6):545-553.DOI:10.1007/s00234-017-1847-6．
• [8]ORSINI F,FUMAGALLI S,CSASZAR E,et al.Mannose-Binding Lectin Drives Platelet Inflammatory Phenotype and Vascular Damage After Cerebral Ischemia in Mice via IL(Interleukin)-1α[J].Arterioscler Thromb Vasc Biol,2018,38(11):2678-2690.DOI:10.1161/ATVBAHA.118.311058．
• [9]MAO L,LI P,ZHU W,et al.Regulatory T cells ameliorate tissue plasminogen activator-induced brain haemorrhage after stroke[J].Brain,2017,140(7):1914-1931.DOI:10.1093/brain/awx111．
• [10]LI S,DAI Q,YU J,et al.Identification of IL-17A-derived neural cell type and dynamic changes of IL-17Ain serum/CSF of mice with ischemic stroke[J].Neurol Res,2017,39(6):552-558.DOI:10.1080/01616412.2017.1315863．
• [11]GELDERBLOM M,GALLIZIOLI M,LUDEWIG P,et al.IL-23(Interleukin-23)-Producing Conventional Dendritic Cells Control the Detrimental IL-17(Interleukin-17)Response in Stroke[J].Stroke,2018,49(1):155-164.DOI:10.1161/STROKEAHA.117.019101．
• [12]DOLATI S,AHMADI M,KHALILI M,et al.Peripheral Th17/Treg imbalance in elderly patients with ischemic stroke[J].Neurol Sci,2018,39(4):647-654.DOI:10.1007/s10072-018-3250-4．
• [13]BAJNOK A,BERTA L,ORBAN C,et al.Cytokine production pattern of T lymphocytes in neonatal arterial ischemic stroke during the first month of life-a case study[J].J Neuroinflammation,2018,15(1):191.DOI:10.1186/s12974-018-1229-y．
• [14]KONG T,PARK J M,JANG J H,et al.Immunomodulatory effect of CD200-positive human placenta-derived stem cells in the early phase of stroke[J].Exp Mol Med,2018,50(1):e425.DOI:10.1038/emm.2017.233．
• [15]ZHANG H,NIU H,YUAN X,et al.Trimetazidine combined with berberine on endothelial function of patients with coronary heart disease combined with primary hypertension[J].Exp Ther Med,2018,16(2):1318-1322.DOI:10.3892/etm.2018.6278．
• [16]LI R,TANG X,JING Q,et al.The effect of trimetazidine treatment in patients with type 2diabetes undergoing percutaneous coronary intervention for AMI[J].Am J Emerg Med,2017,35(11):1657-1661.DOI:10.1016/j.ajem.2017.05.024．
• [17]DENORME F,MANNE B K,PORTIER I,et al.Platelet necrosis mediates ischemic stroke outcome in mice[J].Blood,2020,135(6):429-440.DOI:10.1182/blood.2019002124．
• [18]LYDEN P.Using the National Institutes of Health Stroke Scale:A Cautionary Tale[J].Stroke,2017,48(2):513-519.DOI:10.1161/STROKEAHA.116.015434．
• [19]HASAN T F,RABINSTEIN A A,MIDDLEBROOKSE H,et al.Diagnosis and Management of Acute Ischemic Stroke[J].Mayo Clinic Proc,2018,93(4):523-538.DOI:10.1016/j.mayocp.2018.02.013．
• [20]RAMBAUD T,LEGRIS N,BEJOT Y,et al.Acute ischemic stroke in adolescents[J].Neurology,2020,94(2):e158-e169.DOI:10.1212/WNL.0000000000008783．
• [21]ZHAO X P,ZHAO Y,QIN X Y,et al.Non-invasive Vagus Nerve Stimulation Protects Against Cerebral Ischemia/Reperfusion Injury and Promotes Microglial M2Polarization Via Interleukin-17A Inhibition[J].JMol Neurosci,2019,67(2):217-226.DOI:10.1007/s12031-018-1227-7．
• [22]SUN W,DING Z,XU S,et al.Crosstalk between TLR2and Sphk1in microglia in the cerebral ischemia/reperfusion-induced inflammatory response[J].Int J Mol Med,2017,40(6):1750-1758.DOI:10.3892/ijmm.2017.3165．
• [23]HE X,LI S,LIU B,et al.Major contribution of the 3/6/7class of TRPC channels to myocardial ischemia/reperfusion and cellular hypoxia/reoxygenation injuries[J].Proc Natl Acad Sci U S A,2017,114(23):E4582-E4591.DOI:10.1073/pnas.1621384114．
• [24]PENG L,YIN J,WANG S,et al.TGF-β2/Smad3Signaling Pathway Activation Through Enhancing VEGFand CD34 Ameliorates Cerebral Ischemia/Reperfusion Injury After Isoflurane Post-conditioning in Rats[J].Neurochem Res,2019,44(11):2606-2618.DOI:10.1007/s11064-019-02880-8．
• [25]LOU Z,WANG A P,DUAN X M,et al.Upregulation of NOX2and NOX4 Mediated by TGF-βSignaling Pathway Exacerbates Cerebral Ischemia/Reperfusion Oxidative Stress Injury[J].Cell Physiol Biochem,2018,46(5):2103-2113.DOI:10.1159/000489450．
• [26]刘冲．急性脑梗死患者血清IL-8、IL-17、IL-18水平变化[J]．中国实用神经疾病杂志，2013,16(3):32-33．
• [27]GELDERBLOM M,WEYMAR A,BERNREUTHERC,et al.Neutralization of the IL-17axis diminIshes neutrophil invaslon and protects from ischemic stroke[J].Blood,2012,120(18):3793-3802.DOI:10.1182/blood-2012-02-412726．
• [28]NOH M Y,LEE W M,LEE S J,et al.Regulatory Tcells increase after treatment with poly(ADP-ribose)polymerase-1inhibitor in ischemic stroke patients[J].Int Immunopharmacol,2018,60:104-110.DOI:10.1016/j.intimp.2018.04.043．
• [29]苏建，刘辉，耿海威，等．不同剂量乌司他丁对大面积脑梗死患者转化生长因子β1和预后的影响[J]．中国实用神经疾病杂志，2018,21(22):63-68.DOI:10.12083/SYSJ.2018.22.529．
• [30]ZHOU Z,ZHANG J,LI X,et al.Protein microarray analysis identifies key cytokines associated with malignant middle cerebral artery infarction[J].Brain Behav,2017,7(8):e00746.DOI:10.1002/brb3.746．
• [31]WANG Z,ZHOU Y,YU Y,et al.Lipopolysaccharide preconditioning increased the level of regulatory B cells in the spleen after acute ischaemia/reperfusion in mice[J].Brain Res,2018,1701:46-57.DOI:10.1016/j.brainres.2018.05.036．
• [32]TANG S G,LIU X Y,WANG S P,et al.Trimetazidine prevents diabetic cardiomyopathy by inhibiting Nox2/TRPC3-induced oxidative stress[J].J Pharmacol Sci,2019,139(4):311-318.DOI:10.1016/j.jphs.2019.01.016．
• [33]PETROVICS L,NAGY T,HARDI P,et al.The effect of trimetazidine in reducing the ischemia-reperfusion injury in rat epigastric skin flaps[J].Clin Hemorheol Microcirc,2018,69(3):405-415.DOI:10.3233/CH-170335．
• [34]AMINI N,SARKAKI A,DIANAT M,et al.Protective effects of naringin and trimetazidine on remote effect of acute renal injury on oxidative stress and myocardial injury through Nrf-2regulation[J].Pharmacol Rep,2019,71(6):1059-1066.DOI:10.1016/j.pharep.2019.06.007.