急性脑梗死感染对抗氧化能力与血小板参数的影响
刘云红 孙明洁△ 张佑健 马 冰
河南省人民医院,河南 郑州 450003
基金项目:2017年度河南省医学科技攻关计划项目(编号:201702214)
作者简介:刘云红,Email:lyhhxf@163.com
△通信作者:孙明洁,Email:lhwsmj@126.com
【摘要】 目的 探讨急性脑梗死合并感染患者抗氧化能力与血小板参数的变化。方法 选取2016-01—2017-12河南省人民医院收治的急性脑梗死合并感染患者67例为研究组,同时选取同期入院治疗的脑梗死未合并感染患者70例为对照组,分别检测2组抗氧化能力指标和血小板参数,分析急性脑梗死感染对抗氧化能力和血小板参数的影响。另将研究组按照不同感染程度分组,分析急性脑梗死不同感染程度患者的抗氧化能力指标和血小板参数变化。结果 研究组总抗氧化能力(TAC)、过氧化氢酶(CAT)、超氧化物岐化酶(SOD)等抗氧化能力指标与血小板平均容积(MPV)、血小板体积分布宽度(PDW)、血小板计数(PLT)及大型血小板比率(P-LCR)等血小板参数均明显差于对照组,差异有统计学意义(P<0.05);研究组重度感染患者抗氧化能力指标和血小板参数均明显差于轻度感染者,差异有统计学意义(P<0.05)。结论 脑梗死合并感染患者抗氧化能力指标和血小板参数明显较无感染患者较差,且随着感染程度的加重越来越差,治疗过程中应给予充分重视。
【关键词】 急性脑梗死;感染;抗氧化能力;血小板参数;过氧化氢酶
【中图分类号】 R743.33 【文献标识码】 A 【文章编号】 1673-5110(2019)02-0144-05 DOI:10.12083/SYSJ.2019.02.028
Effect of infection on the anti-oxidative capacity and platelet parameter in acute cerebral infarction patients
LIU Yunhong,SUN Hongjie,ZHANG Youjian,MA Bing
Henan Province People's Hospital,Zhengzhou 450003,China
【Abstract】 Objective To discuss the variations of the anti-oxidative capacity and platelet parameter in co-infected patients with the acute cerebral infarction (ACI).Methods Sixty-seven co-infected patients with ACI and seventy patients with ACI without infection admitted to our hospital from January 2016 to December 2017 were served as a research group and a control group,respectively.The total anti-oxidative capacity (TAC) and platelet parameter of both groups were measured.The effect of ACI and infection level on TAC and platelet parameter were studied.Results There is a significant difference about TAC,CAT,SOD,MPV,PDW,PLT and P-LCR in the research group and control group (P<0.05).The anti-oxidative capacity and platelet parameter in the severe infection were lower than the mild infection (P<0.05).Conclusion The co-infected patients with ACI decreased the anti-oxidative capacity and platelet parameter,and the more severe infection,the worse.More attention should be given to in the treatment of the co-infected patients with ACI.
【Key words】 Acute cerebral infarction;Infection;Anti-oxidative capacity;Platelet parameter;Catalase
急性脑梗死发病急,病情危重,可引起不同程度的脑功能和肢体功能障碍,免疫力低下。因此,更容易合并感染,而感染又会加重基础疾病,诱发重要脏器功能衰竭,对患者生命健康安全构成威胁[1-2]。研究报道,急性脑梗死合并感染后患者抗氧化能力和血小板指标均发生明显变化,而抗氧化能力和血小板参数均与机体整体状态密切相关,其变化程度可预测疾病的严重程度,研究价值极高[3]。本研究通过分析急性脑梗死合并感染患者抗氧化能力和血小板参数的变化,旨在为临床应用该指标对急性脑梗死的恢复治疗提供帮助。
1 资料和方法
1.1 病例资料 选取2016-01—2017-12河南省人民医院收治的急性脑梗死合并感染患者67例为研究组,男42例,女25例,年龄45~79(56.47±7.26)岁,神经功能缺损评分(26.85±5.37)分。感染部位:呼吸道感染38例(56.72%),泌尿系统感染16例(23.88%),胃肠道感染9例(13.43%),皮肤及软组织感染4例(5.97%),其中重度感染18例,中度感染28例,轻度感染21例。同时选取急性脑梗死未合并感染70例为对照组,男46例,女24例,年龄45~80(57.04±7.61)岁,神经功能缺损评分(27.39±6.02)分。入组标准:(1)急性脑梗死符合卫生部疾病控制司、中华医学会神经病学分会制定的《中国脑血管病防治指南》中相关诊断标准,并经头颅MRI和CT检查确诊;(2)感染诊断符合中华人民共和国卫生部制定的《医院感染诊断标准(试行)》中相关诊断标准;(3)无合并脑出血或占位性病变;(4)患者知情同意。排除标准:(1)肿瘤患者;(2)合并肝肾衰竭、充血性心力衰竭和血液系统疾病患者;(3)半年内有大的手术史、外伤史患者;(4)入院前服用改变凝血功能药物患者。尊重患者知情同意权,签订知情通知书,自愿参加本研究,并报请本院伦理委员会批准。2组性别、年龄、基础病情等一般资料比较差异无统计学意义(P>0.05),具有可比性。
1.2 方法 抽取空腹外周静脉血3 mL,应用XT-1800i全自动五分类细胞分析仪(日本希森美康株式会社)检测血小板相关参数;应用酶联免疫法检测抗氧化能力指标,总抗氧化能力(TAC)、过氧化氢酶(CAT)、超氧化物岐化酶(SOD)等试剂盒均由南京建成生物工程公司提供,检测步骤严格按照试剂盒说明执行。
1.3 统计学方法 采用SPSS 14.0统计学软件,计量资料用均数±标准差(x±s)表示,行t检验;计数资料用率(%)表示,行χ2检验;单因素多样本行方差F检验,以P<0.05为差异有统计学意义。
2 结果
2.1 2组抗氧化能力指标和血小板参数比较 研究组TAC、CAT、SOD等抗氧化能力指标与MPV、PDW、PLT及P-LCR等血小板参数均明显差于对照组,差异有统计学意义(P<0.05)。见表1、表2。
2.2 研究组不同感染程度患者抗氧化能力指标和血小板参数比较 研究组重度感染患者抗氧化能力指标和血小板参数均明显差于中度和轻度感染者,差异有统计学意义(P<0.05)。见表3、表4。
表1 2组抗氧化能力指标比较 (x±s)
Table 1 Comparison of antioxidant ability to two groups (x±s)
组别 |
n |
TAC(U/mL) |
CAT(nU/mL) |
SOD(nU/mL) |
研究组 |
67 |
8.04±0.85 |
35.81±3.92 |
70.89±6.92 |
对照组 |
70 |
10.26±1.31 |
41.92±4.24 |
81.43±7.54 |
t值 |
|
11.7103 |
8.7477 |
8.5137 |
P值 |
|
<0.001 |
<0.001 |
<0.001 |
表2 2组血小板参数比较 (x±s)
Table 2 Comparison of platelet parameter in two groups (x±s)
组别 |
n |
MPV(fL) |
PDW(fL) |
PLT(×109个/L) |
P-LCR/% |
研究组 |
67 |
12.83±1.21 |
16.03±1.82 |
155.31±14.29 |
42.89±4.94 |
对照组 |
70 |
11.01±1.04 |
13.64±1.67 |
171.92±16.73 |
36.90±3.97 |
t值 |
|
9.454 4 |
8.013 9 |
6.235 8 |
7.839 5 |
P值 |
|
<0.001 |
<0.001 |
<0.001 |
<0.001 |
表3 研究组不同感染程度患者抗氧化能力指标比较 (x±s)
Table 3 Comparison of antioxidant capacity in patients with different infection degrees (x±s)
感染程度 |
n |
TAC(U/mL) |
CAT(nU/mL) |
SOD(nU/mL) |
重度 |
18 |
6.15±0.68 |
32.24±3.38 |
65.51±6.68 |
中度 |
28 |
8.78±0.39 |
36.91±4.02 |
73.49±6.88 |
轻度 |
21 |
10.31±0.27 |
42.29±4.31 |
81.35±7.52 |
F值 |
|
405.7 |
31.55 |
24.62 |
P值 |
|
<0.001 |
<0.001 |
<0.001 |
表4 研究组不同感染程度患者血小板参数比较 (x±s)
Table 4 Comparison of different degree of infection in patients with platelet parameter (x±s)
感染程度 |
n |
MPV(fL) |
PDW(fL) |
PLT(×109个 /L) |
P-LCR/% |
重度 |
18 |
14.33±1.29 |
17.83±1.91 |
141.96±12.39 |
46.01±4.54 |
中度 |
28 |
12.11±1.14 |
15.24±1.73 |
157.22±13.73 |
42.97±4.18 |
轻度 |
21 |
10.46±1.01 |
13.09±1.57 |
173.15±16.42 |
36.15±3.76 |
F值 |
|
55.56 |
36.27 |
23.14 |
29.72 |
P值 |
|
<0.001 |
<0.001 |
<0.001 |
<0.001 |
3 讨论
急性脑梗死患者的微循环状态较差,更易合并感染,而患者感染后,对急性脑梗死的恢复又进一步造成影响[4-5]。因此,对急性脑梗死并发感染的控制和预防愈加重要。研究报道,对于急性脑梗死合并感染者,抗氧化能力和血小板参数是两个极具代表性的指标[6-7]。急性脑梗死形成时,由于自由基损伤,解毒系统失活,致氧化应激损伤,氧化剂过剩,机体脑组织中抗氧化防御系统紊乱,过量的氧自由基作用会使细胞膜产生脂质过氧化反应,导致质膜被破坏,形成功能障碍,继而引起神经元调亡和死亡[8-11]。研究证实,大脑有较强的抗氧化应激损伤能力,主要通过抗氧化剂和超氧化物岐化酶(SOD)的作用清除机体内氧化应激反应所形成的过剩自由基,其含量可部分反映机体清除自由基的能力,间接反映急性脑梗死的严重程度[12-14]。过氧化氢酶(CAT)能迅速清除细胞内代谢产生的毒素,保护机体巯基酶,通过清除机体内的过氧化氢和脂质过氧化物,阻断氧自由基对细胞膜的损伤,是生物体内的重要抗氧化物[15-18]。本研究中,研究组TAC、CAT、SOD等抗氧化能力指标明显低于对照组,重度感染患者明显低于中度和轻度感染者,提示TAC、CAT、SOD等抗氧化能力指标与急性脑梗死合并感染密切相关,含量越低说明症状越严重[19-20]。
急性脑梗死患者发生感染时,机体会产生免疫系统紊乱和凝血功能障碍,而凝血系统中的血小板参与介导感染患者的凝血功能和全身炎症网络效应,其数量与形态变化,可提示炎性反应状态和疾病严重程度[21-25]。研究表明[26-30],机体在脑梗死发生过程中,血小板被激活,形态也由盘状转变为球状,膜表面积增加。另外,血栓形成过程会消耗大量血小板,促使骨髓和储存池释放体积更大、活性更高的新血小板,新血小板通过黏附及激活循环系统中的单核细胞促使梗死后炎性反应[31-43]。
本研究显示,观察组MPV、PDW和P-LCR值较对照组明显升高,PLT计数明显降低(P<0.05)。这可能因为机体在严重炎性反应时,由于骨髓代偿反应导致巨核细胞增生,使骨髓中巨核细胞代谢和血小板生成及活性紊乱,引起MPV升高。但巨核细胞产生的血小板本身并不成熟,且大小不一、形态各异,体积分布不均,致PDW增大[44-45]。而炎性反应所导致的血管内皮细胞损伤,激活了内源性凝血系统,使血小板过度聚集,形成微血栓,加剧了PLT消耗性减少。
本研究进一步分析了脑梗死合并不同程度感染患者血小板参数的变化,结果表明,MPV、PDW和P-LCR值越高,PLT越低,合并感染越严重,说明血小板参数值能够表现急性脑梗死合并感染的严重程度,对该类患者的诊断与治疗有积极的指导意义。因此,机体抗氧化能力和血小板参数检测对于急性脑梗死感染患者的诊断及治疗均有积极的指导意义,但急性脑梗死感染的抗氧化能力研究在临床上尚十分匮乏,作为一项重要的急性脑梗死感染研究指标,在以后的工作中应进行更加细致的研究。
4 参考文献
[1] LIM H H,JEONG I H,AN G D,et al.Early prediction of severity in acute ischemic stroke and transient ischemic attack using platelet parameters and neutrophil-to-lymphocyte ratio[J].J Clin Lab Anal,2018:e22714.
[2] STAR M,FLASTER M.Advances and controversies in the management of cerebral venous thrombosis[J].Neurol Clin,2013,31(3):765-783.
[3] 柯俊吉,王建平.红细胞分布宽度对急性脑梗死患者近期预后的预测价值[J].中国实用神经疾病杂志,2018,21(3):253-257.
[4] SOMEYA H,FUJIWARA H,NAGATA K,et al.Thymosin beta 4 is associated with RUNX 2 expression through the Smad and Akt signaling pathways in mouse dental cpithelial cclls[J].Int J Mol Med,2015,35(5):1 169-1 178.
[5] 张宏伟,赵俊娜,李舟,等.急性脑梗死卒中相关性肺炎的危险因素分析[J].中国实用神经疾病杂志,2017,20(8):68-70.
[6] MUNDAY J C,EZE A A,BAKER N,et al.Trypanoso-ma brucei aquag-lyceroporin 2 is a high-affinity transporter for pentamidine and melaminophenyl arsenic drugs and the ma in genetic determinantof resistance to of resistance to these drugs[J].J Antimicrob Chemother,2014,69(3):651-663.
[7] KUDOH R,MIKAMI K,KITAJIMA M,et al.Spontaneous Micro-Aggregation of Platelets Predicts Clinical Outcome in Acute Ischemic Stroke[J].J Stroke Cerebrovasc Dis,2018,27(8):2 074-2 081.
[8] 王裕鹏,孙石磊.抗氧化剂与脑小血管病关系的研究进展[J].中国实用神经疾病杂志,2017,20(11):81-83;封三.
[9] CHEN S H,LIN M T,CHANG C P.Ischemic and oxidative damage to the hy-pothalamus may be responsible for heat stroke[J].Curr Neuropharmacol,2013,11(2):129-140.
[10] LI W,XIE X,WEI D,et al.Baseline platelet parameters for predicting early platelet response and clinical outcomes in patients with non-cardioembolic ischemic stroke treated with clopidogrel[J].Oncotarget,2017,8(55):93 771-93 784.
[11] SPORNS P B,HANNING U,SCHWINDT W,et al.Ischemic Stroke:What Does the Histological Composition Tell Us About the Origin of the Thrombus?[J].Stroke,2017,48(8):2 206-2 210.
[12] SELVARATNAM J,ROBAIRE B.Overexpression of catalase in mice reduces age-related oxidative stress and maintains sperm production[J].Exp Gerontol,2016,84:12-20.
[13] BAYAR N,KÜÇÜKSEYMEN S,ERKAL Z,et al.Relationship between mean platelet volume and ischemic stroke in patients with patent foramen ovale[J].Turk Kardiyol Dern Ars,2017,45(1):9-15.
[14] CELIK T,KAYA M G,AKPEK M,et al.Predictive value ofadmission platelet volume indices for in-hosp“al major adverse cardiovascular events in acute sT-segment elevation myocaldial inftion[J].Angiologr,2015,66 (2):155-162.
[15] TASDEMIR S,ERDEM H B,SAHIN I,et al.Correl-ation with Platelet Parameters and Genetic Markers of Thrombophilia Panel (Factor II g.20210G>A,Factor V Leiden,MTHFR (C677T,A1298C),PAI-1,β-Fibrinogen,Factor XIIIA (V34L),Glycoprotein IIIa (L33P) in Ischemic Strokes[J].Neuromolecular Med,2016,18(2):170-176.
[16] CHEN Y,XIAO Y,LIN Z,et al.The Role of Circulating Platelets Microparticles and Platelet Parameters in Acute Ischemic Stroke Patients[J].J Stroke Cerebrovasc Dis,2015,24(10):2 313-2 320.
[17] SCHMALBACH B,STEPANOW O,JOCHENS A,et al.Determinants of platelet-leukocyte aggregation and platelet activation in stroke[J].Cerebrovasc Dis,2015,39(3/4):176-80.
[18] 黄海峰.ABCD2 评分对短暂性脑缺血发作患者早期双抗血小板治疗的指导价值[J].中国实用神经疾病杂志,2016,19(19):109-110.
[19] MARQUARDT L,ANDERS C,BUGGLE F,et al.Leukocyte-platelet aggregates in acute and subacute ischemic stroke[J].Cerebrovasc Dis,2009,28(3):276-282.
[20] SALAT D,PENALBA A,GARCA-BERROCOSOT,et al.Immunological biomarkers improve theaccuracy of clinical risk models of infection in the acute phase of ischemic stroke[J].Cerebrovascular diseases,2013,35(3):220-227.
[21] ABELA L,TOELLES P,HACKENBERG A,et al.Fatal outcome of rhino-orbital-cerebral mucormycosis due to bilateral internal carotid occlusion in a child after hematopoietic stem cell transplantation[J].Pediatr Infect Dis J,2013,32(10):1 149-1 150.
[22] WALTER U,KOLBASKE S,PATEJDL R,et al.Insu-lar stroke is associated with acute sympathetic hyperactivation and immunodepression[J].Eur J Neurol,2013,20(1):153-159.
[23] 曾倩,龙秀英,宋春江.复发性脑梗死相关危险因素分析[J].中国实用神经疾病杂志,2018,21(1):37-39.
[24] BRYANTP A,NORONHA J.Acute neck infection[J].N Engl J Med,2014,371(16):1 534.
[25] JIN R,ZHU X,LI U L,et al.Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice[J].Stroke,2013,44(4):1 135-1 143.
[26] RATNASINGHAM Y,KRISTENSEN L H,GAMMELGAARD L,et al.Arterial ischemic stroke as a complication to disseminated infection with Fusobacterium necrophorum[J].Neuropediatrics,2014,45(2):120-122.
[27] DEVOS D,SEVIN M,DE GAALON S,et al.Management of ischemic stroke in the hyperacute phase[J].Panminerva Medica,2013,55(1):59-78.
[28] STAR M,FLASTER M.Advaces and controversies in the management of cerebral venous thrombosis[J].Neurol Clin,2013,31(3):765-783.
[29] SOMEYA H,FUJIWARA H,NAGATA K,et al.Thymosin beta 4 is associated with RUNX 2 expression through the Smad and AKt signaling pathways in mouse dental cpithelial cclls[J].Int J Mol Med,2015,35(5):169-178.
[30] MUNDAY J C,EZEA A,BAKER N,et al.Trypanoso-ma brucei aquag-lyceroporin 2 is a high-affinity trans-porter for pentamidine and melaminophenyl arsenic drugs and the ma in genetic determinantof resistance to of resistance to these druds[J].JAntimierob Chemother,2014,69(3):651-663.
[31] CHEN S H,LIN M T,CHANG C P.Ischemic and oxi-dative damage to the hy-pothalamus may be reaponsi-ble for heat stroke[J].Curr Neuropharmacol,2013,11(2):129-140.
[32] SELVARATNAM J,ROBAIRE B.Overexpression of catalase in mice reduces age-related oxidative stress and maintains sperm prodyction[J].Exp Gerontol,2016,84:12-20.
[33] CELIK T,KAYA M G,AKPEK M,et al.Predictivev-alue ofadmission platelet volume indices for in-hosp ”al major adverse cardiovascular events in acute sT-segment elevation myocardial inftion[J].Angiologr,2015,66(2):155-162.
[34] JIN R,ZHU X,LI U L,et al.Simvastatin attenuates stroke-induccd splenic atophy and lung susceptibility to spontaneous baceoal infection in mice[J].Stroke,2013,44(4):1 135-1 143.
[35] SALAT D,PENALBA A,GARCIA-BERROCOSOT,et al.Immunological biomarkers improve theaccuracy of clinical risk models of infection in the acute phase of ischemic stroke[J].Cerebrovasc Dis,2013,35(3):220-227.
[36] ABELA L,TOELLES P,HACKENBERG A,et al.Fatal outcome of rhino-orbital-cerebral mucormycosis due to bilateral internal carotid occlusion in a child after hematopoietic stem cell transplantation[J].Pediatr Infect Dis J,2013,32(10):1 149-1 150.
[37] WALTERU,KOLBASKES,PATEJDLR,et al.Insular stroke is associated with acute sympathetic hyperactivation and immunodepression[J].EurJNeurol,2013,20(1):153-159.
[38] JIN R,ZHU X,LIU L,et al.Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibilityto spontaneous bacterial infection in mice[J].Stroke,2013,44(4):1 135-1 143.
[39] RATNASINGHAM Y,KRISTENSEN L H,GAMME-LGAARD L,et al.Arterial ischemic strokerium necrophorum[J].Neurpediatrics,2014,45(2):120-122.
[40] DEVOS D,SEVIN M,DEGAALONS,etal.Manage-ment of ischemic stroke in the hyperacute phase[J].Panminerva Medica,2013,55(1):59-78.
[41] HOU H,ZHANG G,WANG H,et al.High matrix metalloproteinase-9 expression inures angiogenesis and basement membrane degradation in atroke prone spontanously hypertensive rats after cerebrane infarction[J].Neural Regen Res,2014,9(11):1 154-1 162.
[42] SOMEYA H,FUJIWARA H,NAGASA K,et al.Thymosin beta 4 is associated with RUNX2 expression through the Smad and AKt signaling pathways in mouse dental epithelial cells[J].Int J Mol Med,2015,35(5):1 169-1 178.
[43] METALS PATE KA,LYONS CE,DORSEY JL,et al.Platelet actrivation and platelet-monocyte aggregate formation contribute to decreased platelet countduring acute simian immunodeficiency virus infection in pig-tailed marcaques[J].J Infeet Dis,2013,208(6):874-883.
[44] ARMAN M,KRAUEL K,TILLEY DO,et al.Amplifieation of bacteria induced platelet activation is triggered by FeyRIIA,integrity aIIbβ3,and platelet factor 4[J].Boos,2014,123(20):3 166-3 174.
[45] FAMAKIN BM.The immune response to acute focal cerebral is chemistry and associated post-stroke immunodepression:a focused review[J].Aging Dis,2014,5(5):307-326.
(收稿2018-04-25)
本文责编:夏保军
本文引用信息:刘云红,孙明洁,张佑健,马冰.急性脑梗死感染对抗氧化能力与血小板参数的影响[J].中国实用神经疾病杂志,2019,22(2):144-148.DOI:10.12083/SYSJ.2019.02.028
Reference information:LIU Yunhong,SUN Hongjie,ZHANG Youjian,MA Bing.Effect of infection on the anti-oxidative capacity and platelet parameter in acute cerebral infarction patients[J].Chinese Journal of Practical Nervous Diseases,2019,22(2):144-148.DOI:10.12083/SYSJ.2019.02.028