急性脑梗死患者血清IL-6、TNFα、S-100b变化及临床意义
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摘要
目的:分析急性脑梗死患者血清IL-6、TNFα、S-100b的动态变化规律及临床意义,探讨IL-6、TNFα、S-100b在急性脑梗死病理损伤中可能的作用机制。
方法:选择发病24小时以内的符合试验入选条件的颈内动脉系统急性脑梗死患者58例,同时收集相匹配的同期体检者30例作为对照组,用ELISA法测定血清IL-6、TNFα、S-100b浓度。病例组进行动态监测(于发病第1d、3d、7d、14d抽血),并同时记录患者神经功能缺损评分(NIHSS)。所有急性脑梗死患者依据发病后48-72h的脑CT或MR扫描结果计算脑梗死体积。
结果:1.急性脑梗死患者血清IL-6、TNFα、S-100b发病当天就明显增高,IL-6、TNFα发病后第1d即达高峰,S-100蛋白第3d达高峰。其后浓度随时间的推移逐渐下降。梗塞体积大的患者血清IL-6、TNFα、S-100b蛋白更高且持续时间更长。
2.血清IL-6、TNFα、S-100b的峰值浓度和脑梗死体积、NIHSS评分呈正相关。
3.发病后进展性脑卒中患者血清IL-6、TNFα和S-100b蛋白高峰水平高于无进展性脑卒中患者。
结论:急性脑梗死患者血清IL-6、TNFα和S-100b蛋白水平升高,他们可能从不同环节参与脑缺血后病理损伤,与进展性脑卒中相关。血清水平值能够反映脑缺血后病理损伤的程度和脑梗死体积大小,可作为急性脑梗死病人病情加重的标志物。
Abstrct:Objective:To analyze the changes and clinical significance of IL-6,TNFα, S-100b.and to explore their pathologic mechanism in the brain ischemia.
Methods:58 patients consecutively admittied with first-ever ischemic cerebral infarction within the first 24 hours from onset were included,and 30 healthy subjects were selected as controls.The serum level of IL-6,TNFαand S-100b was measured by enzyme linked immunosorbent assay.All the paitents that experienced stroke were observed on the 1st,3rd,7th day,the severity of stroke was scored at the same time using the NIH stroke Scale(NIHSS).The subsequent volume of brain lesion as a consequence of stroke was measured by CT or MRI within 48-72h after the onset.
Results:1.Both the serum levels of IL-6,TNFαand S-100b were significantly higher in patients within the first day after the onset than those of the contros.IL-6,TNFa attain the peaks within 24 hours after the attact,athough the S-100 peak was arrived on the 3rd day.They all decreased gradually after the peaks.
2.There was a positive correlation between both the peak levels of IL-6,TNFαand S-100b and the infarct volume and NIHSS..
3.Higher levels of IL-6,TNFαand S-100b in serum inpatients with neurological deterioration compared with paitents who retained clinically stable or improved course.
Conclusion:The serum levels of IL-6,TNFαand S-100b were upregulated,which may take part in the pathogenesis of acute cerebal infarction by deferent parthway.The levels of IL-6,TNFαand S-100b may reflect both the degree of pathologic lesion and the infarct volum.They may be markes for outcome in acute ischemic stroke.
方法:选择发病24小时以内的符合试验入选条件的颈内动脉系统急性脑梗死患者58例,同时收集相匹配的同期体检者30例作为对照组,用ELISA法测定血清IL-6、TNFα、S-100b浓度。病例组进行动态监测(于发病第1d、3d、7d、14d抽血),并同时记录患者神经功能缺损评分(NIHSS)。所有急性脑梗死患者依据发病后48-72h的脑CT或MR扫描结果计算脑梗死体积。
结果:1.急性脑梗死患者血清IL-6、TNFα、S-100b发病当天就明显增高,IL-6、TNFα发病后第1d即达高峰,S-100蛋白第3d达高峰。其后浓度随时间的推移逐渐下降。梗塞体积大的患者血清IL-6、TNFα、S-100b蛋白更高且持续时间更长。
2.血清IL-6、TNFα、S-100b的峰值浓度和脑梗死体积、NIHSS评分呈正相关。
3.发病后进展性脑卒中患者血清IL-6、TNFα和S-100b蛋白高峰水平高于无进展性脑卒中患者。
结论:急性脑梗死患者血清IL-6、TNFα和S-100b蛋白水平升高,他们可能从不同环节参与脑缺血后病理损伤,与进展性脑卒中相关。血清水平值能够反映脑缺血后病理损伤的程度和脑梗死体积大小,可作为急性脑梗死病人病情加重的标志物。
Abstrct:Objective:To analyze the changes and clinical significance of IL-6,TNFα, S-100b.and to explore their pathologic mechanism in the brain ischemia.
Methods:58 patients consecutively admittied with first-ever ischemic cerebral infarction within the first 24 hours from onset were included,and 30 healthy subjects were selected as controls.The serum level of IL-6,TNFαand S-100b was measured by enzyme linked immunosorbent assay.All the paitents that experienced stroke were observed on the 1st,3rd,7th day,the severity of stroke was scored at the same time using the NIH stroke Scale(NIHSS).The subsequent volume of brain lesion as a consequence of stroke was measured by CT or MRI within 48-72h after the onset.
Results:1.Both the serum levels of IL-6,TNFαand S-100b were significantly higher in patients within the first day after the onset than those of the contros.IL-6,TNFa attain the peaks within 24 hours after the attact,athough the S-100 peak was arrived on the 3rd day.They all decreased gradually after the peaks.
2.There was a positive correlation between both the peak levels of IL-6,TNFαand S-100b and the infarct volume and NIHSS..
3.Higher levels of IL-6,TNFαand S-100b in serum inpatients with neurological deterioration compared with paitents who retained clinically stable or improved course.
Conclusion:The serum levels of IL-6,TNFαand S-100b were upregulated,which may take part in the pathogenesis of acute cerebal infarction by deferent parthway.The levels of IL-6,TNFαand S-100b may reflect both the degree of pathologic lesion and the infarct volum.They may be markes for outcome in acute ischemic stroke.
引文
1.Tezono K,Sarker KP,kikuchi H,et al,Bioactivity of the vascular endothelial growth factor trapped in fibrin clotss Production of IL-6 and IL-8 in monocytes by fibrin clots[J],Haemostasis,2001;31(2):71-79
2.Matsui T,Mori T,Tateishi N,et al,Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats,J Cereb Blood Flow Metab,2002Jun,22(6):711-722.
3.陈兴洲,李宏建,陆兵勋.恶化性卒中[J].国外医学:脑血管病分册,2000,8(2):109.
4.陈明生,朱瑞芬,詹庆盈.脑梗塞患者血清TNF、IL含量的变化及其临床意义的研究[J].中国神经免疫学和神经病学杂志,2001;1(8):32-34.
5.Selzner N,Selzner M,Odermatt B,et al.ICAM-1 triggers liver regeneration through leukocyte recruitment and kupffer cell-dependent release of TNF-alpha/IL-6 in mice[J].gastroemerology,2003,124(3):692-700.
6.Kouwenhoven M,Carlstrom C,Ozenci V,et al.Matrix metalloproteinase and cytokine profiles in monocytes over the course of stroke.J Clin Immunol,2001,Sep;21(5):365-375.
7.Margaglione.Genetic modulation of plasma fibrinogen concentration:Possible importance of interleukin -6.J Thromb Thrombolysis,1996,3(1):51-56.
8.Vila N,Reverter JC,Yague J,etal.Interaction between interleukin-6 and the natural solicoagulant system in acut stroke.J interferon Cytokin Res,2000,20(3):325-329.
9.Zhu DY,Li R,Liu GQ,et al.Tumor necrosis factor alpha enhances the cytotoxicity induced by nitric oxide in cultured cerebral endothelial cell.Life Sci,2000,66:1325-1335.
10.钟照平,李国忠,李呼伦,人缺血脑组织中TNF-α和IL-1β的表达.细胞与分子免疫学杂志,2003 8;19(4):349-350.
11.Offner H,Subramanian S,Parker SM,Afentoulis ME,Vandenbark AA,Eperimental stroke induces massive,rapid activation of the peripheral immune system,J Cereb Blood Flow Metab,2005,Aug24;175(6):4103-4111.
12.Vila N,Castillo J,Davalos A,et al.Proinflammatory Cytokines and early neurological wersing in ischemic.Stroke.2000,31(10):2325-2329.
13.Castellanos M,Castillo J,Garcia MM,et al.Inflammation-mediated damage in progressing lacunar infarctions;a potential therapeutic target,Stroke,2002Apr;33(4):982-987.
14.Foerch C.Singer OC,et al.Evaluation of Serum S-100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction.Arch Neurol.2005 Jul.62(7):1130-1134.
15.Wunderlich MT,Ebert AD,Kratz T,et al.Early neurobehavioral outcome after stroke is relate to release of neurobiochemical markers of brain damage.Stroke,1999,30:1190-1195.
16.雷万龙,袁群芳,姚志彬.局灶脑缺血区星型胶质细胞可塑性变化的实验研究[J].神经解剖学杂志,2000,16(2):123.
17.Vila N,Castillo J,Davalos A,et al.Proinflammatory Cytokines and early neurological wersing in ischemic.Stroke.2000,31(10):2325-2329.
18.李红云,纪晓军,裴海涛等.进展性缺血性卒中[J].国外医学。脑血管疾病分册,2005,13:132-135
19.刘丽萍,王拥军.体温与卒中的关系.国外医学脑血管病分册.2004,12:267-270.
20.Vendrame M,Gemma C,de Mesquita D,et al.Anti-inflammatory effects of human cord blood cells in a rat model of stroke,Stem Cell Dev,2005,14(5):595-604.
1.Offner H,Subramanian S,Parker SM,Afentoulis ME,Vandenbark AA,Eperimental stroke induces massive,rapid activation of the peripheral immune system,J Cereb Blood Flow Metab,2005,Aug24;175(6):4103-4111.
2.Yamashita T,Sawamoto K,Suzuki S,et al.Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice:possible involvement of Star3activation in the protection of neurons,J Neurochem.2005 Jul;94(2):459-468.
3.Xing Z,Gaudie J,Cox G,et al,IL-6 is a anti-inflammatory Cytokime required for controlling local or systemic acute inflammatory response[J],J Clin Invest,1998,101:311
4.Missler U,Wiesmann M,Friedrich C,et al,S-100 protein and Neuron Specific Enolase concentrations in blood as indictors of infarction volume and prognosis in acute ischemic stroke,Stroke,1997,28:1956.
5.Foerch C.Singer OC,et al.Evaluation of Serum S-100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction.Arch Neurol.2005 Jul.62(7):1130-1134.
6.Matsui T,Mori T,Tateishi N,et al,Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats,J Cereb Blood Flow Metab,2002Jun,22(6):711-722.
7.Yasuda Y,Tateishi N,et al.Relationship between S-100beta and GFAP expression in astrocytes during infarction and glial scar formation after mild transient ischemia.Brain Res,2004.Sep 17 1021(1):20-31.
8.Vila N,Castillo J,Davalos A,et al.Proinflammatory Cytokines and early neurological wersing in ischemic.Stroke.2000,31(10):2325-2329.
9.Vila N,Reverter JC,Yague J,etal.Interaction between interleukin-6 and the natural solicoagulant system in acut stroke.J interferon Cytokin Res,2000,20(3):325-329.
10.刘尊敬,杨期东,刘运海等.脑梗死患者血清IL-6和sICAM-1变化及临床意义.中南大学学报医学版,2004;29(3):326-329.
11.Kouwenhoven M,Carlstrom C,Ozenci V,et al.Matrix metalloproteinase and cytokine profiles in monocytes over the course of stroke.J Clin Immunol,2001,Sep;21(5):365-375.
12.Waje-Andreassen U,Krakones J,et al.IL-6,an early marker for outcome in acute ischemic stroke,Acta Neurol scand,2005 Jun,111(6):360-365.
13.钟照平,李国忠,李呼伦,人缺血脑组织中TNF-α和IL-1β的表达.细胞与分子免疫学杂志,2003 8;19(4):349-350.
14.Castellanos M,Castillo J,Garcia MM,et al.Inflammation-mediated damage in progressing lacunar infarctions;a potential therapeutic target,Stroke,2002Apr;33(4):982-987.
15.MontanerJ,Rovira A,Molina CA,et al.Plasmatic level of neuroinflammatory makers predict the extent of difffusion-weighted image iesions in hyperacute stroke J Cereb Blood Flow Metab,2003Dec;23(12):1403-1407.
16.Tezono K,Sarker KP,kikuchi H,et al,Bioactivity of the vascular endothelial growth factor trapped in fibrin clotss Production of IL-6 and IL-8 in monocytes by fibrin clots[J],Haemostasis,2001;31(2):71-79.
17.Rallidisls,Paschos G,Liakos,GK,et al,Dietary alpha-linolenic acid decrease c-reactive protein,serum a myloid A and inteleukin-6 in dyslipidaemic patients[J],Atherosclerosis,2003;167(2):237-242.
18.Bruce AJ,Bioling W,Kindy MS,et al.Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors[J],Nav Med,1996,2(7):188-194.
19.Castillo J,MoroMA,Blanco M,et al.The release of tumor necrosis factor-alpha is associated with ischemic tolerance in humman stroke.Ann Neurol.2003Dec;54(6):811-819.
20.Ang ET,Wong PT,Moochhala S Ng YK,Cytokin changes in the horizontal diagonal band of Broca in the septum after running and stroke:a correlation to glial activation,Neuroscience,2004,129(2):337-347.
21.Dziedzic T,Gryz EA,Turaj W,Slowik A,et al.Serum interleukin-6 soluble receptor in relation to interleukin-6 in stroke patients J Mol Neurosci,2004;24(2):293-298.
22.Pera J Zawadzka M,Kamins Ka B,et al.Influence of chemical and ischemic preconditioning on cytokine expression after focal brain ischemia,J Neurosci Res,2004,Oct 1;78(1):132～140.
23.Foerch C,Otto B,et al.Serum S-100B predits a malignant course of infarction in patients with acute middle cerebral artery occlusion. Stroke,2004 Sep:35(9):2160～2164.
24.Foerch C,du Mesil de Rochemont R,Singer O,et al.S-100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artory occlusion,J Neurol Neurosurg Psychiatry,2003 Mar.74(3):322～325.
25.Infante JR,Martine ZA,Ochoa J,et al.Level of S-100 and neuron-specific enolase in cerebrospinal fluid from subjects with neurological pathologies.Rev Esp Med Nacl.2003 Jul-Aug;22(4):238-243.
2.Matsui T,Mori T,Tateishi N,et al,Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats,J Cereb Blood Flow Metab,2002Jun,22(6):711-722.
3.陈兴洲,李宏建,陆兵勋.恶化性卒中[J].国外医学:脑血管病分册,2000,8(2):109.
4.陈明生,朱瑞芬,詹庆盈.脑梗塞患者血清TNF、IL含量的变化及其临床意义的研究[J].中国神经免疫学和神经病学杂志,2001;1(8):32-34.
5.Selzner N,Selzner M,Odermatt B,et al.ICAM-1 triggers liver regeneration through leukocyte recruitment and kupffer cell-dependent release of TNF-alpha/IL-6 in mice[J].gastroemerology,2003,124(3):692-700.
6.Kouwenhoven M,Carlstrom C,Ozenci V,et al.Matrix metalloproteinase and cytokine profiles in monocytes over the course of stroke.J Clin Immunol,2001,Sep;21(5):365-375.
7.Margaglione.Genetic modulation of plasma fibrinogen concentration:Possible importance of interleukin -6.J Thromb Thrombolysis,1996,3(1):51-56.
8.Vila N,Reverter JC,Yague J,etal.Interaction between interleukin-6 and the natural solicoagulant system in acut stroke.J interferon Cytokin Res,2000,20(3):325-329.
9.Zhu DY,Li R,Liu GQ,et al.Tumor necrosis factor alpha enhances the cytotoxicity induced by nitric oxide in cultured cerebral endothelial cell.Life Sci,2000,66:1325-1335.
10.钟照平,李国忠,李呼伦,人缺血脑组织中TNF-α和IL-1β的表达.细胞与分子免疫学杂志,2003 8;19(4):349-350.
11.Offner H,Subramanian S,Parker SM,Afentoulis ME,Vandenbark AA,Eperimental stroke induces massive,rapid activation of the peripheral immune system,J Cereb Blood Flow Metab,2005,Aug24;175(6):4103-4111.
12.Vila N,Castillo J,Davalos A,et al.Proinflammatory Cytokines and early neurological wersing in ischemic.Stroke.2000,31(10):2325-2329.
13.Castellanos M,Castillo J,Garcia MM,et al.Inflammation-mediated damage in progressing lacunar infarctions;a potential therapeutic target,Stroke,2002Apr;33(4):982-987.
14.Foerch C.Singer OC,et al.Evaluation of Serum S-100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction.Arch Neurol.2005 Jul.62(7):1130-1134.
15.Wunderlich MT,Ebert AD,Kratz T,et al.Early neurobehavioral outcome after stroke is relate to release of neurobiochemical markers of brain damage.Stroke,1999,30:1190-1195.
16.雷万龙,袁群芳,姚志彬.局灶脑缺血区星型胶质细胞可塑性变化的实验研究[J].神经解剖学杂志,2000,16(2):123.
17.Vila N,Castillo J,Davalos A,et al.Proinflammatory Cytokines and early neurological wersing in ischemic.Stroke.2000,31(10):2325-2329.
18.李红云,纪晓军,裴海涛等.进展性缺血性卒中[J].国外医学。脑血管疾病分册,2005,13:132-135
19.刘丽萍,王拥军.体温与卒中的关系.国外医学脑血管病分册.2004,12:267-270.
20.Vendrame M,Gemma C,de Mesquita D,et al.Anti-inflammatory effects of human cord blood cells in a rat model of stroke,Stem Cell Dev,2005,14(5):595-604.
1.Offner H,Subramanian S,Parker SM,Afentoulis ME,Vandenbark AA,Eperimental stroke induces massive,rapid activation of the peripheral immune system,J Cereb Blood Flow Metab,2005,Aug24;175(6):4103-4111.
2.Yamashita T,Sawamoto K,Suzuki S,et al.Blockade of interleukin-6 signaling aggravates ischemic cerebral damage in mice:possible involvement of Star3activation in the protection of neurons,J Neurochem.2005 Jul;94(2):459-468.
3.Xing Z,Gaudie J,Cox G,et al,IL-6 is a anti-inflammatory Cytokime required for controlling local or systemic acute inflammatory response[J],J Clin Invest,1998,101:311
4.Missler U,Wiesmann M,Friedrich C,et al,S-100 protein and Neuron Specific Enolase concentrations in blood as indictors of infarction volume and prognosis in acute ischemic stroke,Stroke,1997,28:1956.
5.Foerch C.Singer OC,et al.Evaluation of Serum S-100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction.Arch Neurol.2005 Jul.62(7):1130-1134.
6.Matsui T,Mori T,Tateishi N,et al,Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats,J Cereb Blood Flow Metab,2002Jun,22(6):711-722.
7.Yasuda Y,Tateishi N,et al.Relationship between S-100beta and GFAP expression in astrocytes during infarction and glial scar formation after mild transient ischemia.Brain Res,2004.Sep 17 1021(1):20-31.
8.Vila N,Castillo J,Davalos A,et al.Proinflammatory Cytokines and early neurological wersing in ischemic.Stroke.2000,31(10):2325-2329.
9.Vila N,Reverter JC,Yague J,etal.Interaction between interleukin-6 and the natural solicoagulant system in acut stroke.J interferon Cytokin Res,2000,20(3):325-329.
10.刘尊敬,杨期东,刘运海等.脑梗死患者血清IL-6和sICAM-1变化及临床意义.中南大学学报医学版,2004;29(3):326-329.
11.Kouwenhoven M,Carlstrom C,Ozenci V,et al.Matrix metalloproteinase and cytokine profiles in monocytes over the course of stroke.J Clin Immunol,2001,Sep;21(5):365-375.
12.Waje-Andreassen U,Krakones J,et al.IL-6,an early marker for outcome in acute ischemic stroke,Acta Neurol scand,2005 Jun,111(6):360-365.
13.钟照平,李国忠,李呼伦,人缺血脑组织中TNF-α和IL-1β的表达.细胞与分子免疫学杂志,2003 8;19(4):349-350.
14.Castellanos M,Castillo J,Garcia MM,et al.Inflammation-mediated damage in progressing lacunar infarctions;a potential therapeutic target,Stroke,2002Apr;33(4):982-987.
15.MontanerJ,Rovira A,Molina CA,et al.Plasmatic level of neuroinflammatory makers predict the extent of difffusion-weighted image iesions in hyperacute stroke J Cereb Blood Flow Metab,2003Dec;23(12):1403-1407.
16.Tezono K,Sarker KP,kikuchi H,et al,Bioactivity of the vascular endothelial growth factor trapped in fibrin clotss Production of IL-6 and IL-8 in monocytes by fibrin clots[J],Haemostasis,2001;31(2):71-79.
17.Rallidisls,Paschos G,Liakos,GK,et al,Dietary alpha-linolenic acid decrease c-reactive protein,serum a myloid A and inteleukin-6 in dyslipidaemic patients[J],Atherosclerosis,2003;167(2):237-242.
18.Bruce AJ,Bioling W,Kindy MS,et al.Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors[J],Nav Med,1996,2(7):188-194.
19.Castillo J,MoroMA,Blanco M,et al.The release of tumor necrosis factor-alpha is associated with ischemic tolerance in humman stroke.Ann Neurol.2003Dec;54(6):811-819.
20.Ang ET,Wong PT,Moochhala S Ng YK,Cytokin changes in the horizontal diagonal band of Broca in the septum after running and stroke:a correlation to glial activation,Neuroscience,2004,129(2):337-347.
21.Dziedzic T,Gryz EA,Turaj W,Slowik A,et al.Serum interleukin-6 soluble receptor in relation to interleukin-6 in stroke patients J Mol Neurosci,2004;24(2):293-298.
22.Pera J Zawadzka M,Kamins Ka B,et al.Influence of chemical and ischemic preconditioning on cytokine expression after focal brain ischemia,J Neurosci Res,2004,Oct 1;78(1):132～140.
23.Foerch C,Otto B,et al.Serum S-100B predits a malignant course of infarction in patients with acute middle cerebral artery occlusion. Stroke,2004 Sep:35(9):2160～2164.
24.Foerch C,du Mesil de Rochemont R,Singer O,et al.S-100B as a surrogate marker for successful clot lysis in hyperacute middle cerebral artory occlusion,J Neurol Neurosurg Psychiatry,2003 Mar.74(3):322～325.
25.Infante JR,Martine ZA,Ochoa J,et al.Level of S-100 and neuron-specific enolase in cerebrospinal fluid from subjects with neurological pathologies.Rev Esp Med Nacl.2003 Jul-Aug;22(4):238-243.