急性缺血性卒中后炎症因子水平与神经功能恢复的关系研究

Relationship between the Levels of Post-stroke Inflammatory Factors and Neurological Function Restoration in Patients with Acute Ischemic Stroke

目的分析急性大动脉粥样硬化性缺血性卒中后炎症因子水平及其与神经神经功能恢复的相关性。方法收集2015年11月-2018年1月中国康复研究中心北京博爱医院神经内科收治的轻中度(NIHSS≤15分)大动脉粥样硬化性急性缺血性卒中患者。分别在入院时、1周、2周、4周进行白细胞计数(white blood cell,WBC)、中性粒细胞计数(neutrophils,NEU)及纤维蛋白原(fibrinogen,Fib)、IL-6、TNF-α等炎症因子的检测,同时进行NIHSS评分;并在发病4周进行mRS评分。根据入组时NIHSS评分,将患者分为轻型卒中(NIHSS 0~4分)和中型卒中(NIHSS 5~15分)两组,比较两组间发病4周内的炎症因子水平。分析WBC、NEU和Fib水平与同期NIHSS的相关性,入院时WBC、NEU和Fib水平与后续随访(1周、2周和4周)时NIHSS以及4周时mRS的相关性。结果研究共入组61例患者,轻型卒中组50例、中型卒中组11例。入院时中型卒中组W B C[(8.87±2.99)×10^(9)/L vs(7.07±2.06)×10^(9)/L,P=0.019]、NEU[(6.38±2.77)×10^(9)/L vs(4.72±1.66)×10^(9)/L,P=0.010]和Fib[3.31(2.74~4.24)g/L vs 2.71(2.36~3.30)g/L,P=0.041]水平均高于轻型卒中组;发病1周时,中型卒中组WBC[(8.80±1.47)×10^(9)/L vs(6.99±2.32)×10^(9)/L,P=0.032]、NEU[(6.16±1.09)×10^(9)/L vs(4.72±2.14)×10^(9)/L,P=0.049]和Fib[3.73(2.92~4.39)vs 2.65(2.25~3.11),P=0.022]水平均高于轻型卒中组;发病2周时,中型卒中组WBC[(8.40±1.68)×10^(9)/L vs(6.89±1.28)×10^(9)/L,P=0.012]、NEU[(5.76±1.46)×10^(9)/L vs(4.59±1.12)×10^(9)/L,P=0.024]仍高于轻型卒中组,但两组Fib水平差异无统计学意义;发病4周时两组的WBC、NEU和Fib水平差异均无统计学意义。两组各个时间点IL-6、TNF-α水平差异均无统计学意义。入院时(r=0.225,P=0.048)、发病1周时(r=0.413,P=0.005)和发病2周(r=0.382,P=0.034)时NIHSS与Fib水平呈正相关;入院时(r=0.257,P=0.046)和发病2周时(r=0.396,P=0.027)NIHSS与NEU水平呈正相关;发病2周时(r=0.451,P=0.011)NIHSS与WBC水平呈正相关。入院时WBC水平与发病2周(r=0.442,P=0.007)和4周(r=0.518,P=0.011)时的NIHSS呈正相关;入院时NEU水平与发病1周(r=0.268,P=0.048)、2周(r=0.402,P=0.015)和4周(r=0.431,P=0.040)时的NIHSS评分呈正相关;入院时Fib水平与发病1周(r=0.318,P=0.023)和2周(r=0.378,P=0.025)时NIHSS呈正相关。结论对于轻中度大动脉粥样硬化性缺血性卒中,发病2周内神经功能缺损程度与Fib和NEU水平呈正相关;中型缺血性卒中在发病2周内的WBC、NEU和Fib水平高于轻型缺血性卒中,该差异在发病4周时逐渐消失。

Objective To analyze the changes of levels of poststroke inflammatory factors,and its correlation with neurological function restoration after acute atherosclerotic ischemic stroke.Methods Patients with mild to moderate(NIHSS≤15 points)acute ischemic stroke due to large vessel atherosclerosis treated in Department of Neurology of Beijing Bo'ai Hospital of China Rehabilitation Research Center from November 2015 to January 2018 were prospectively enrolled in this study.The white blood cell(WBC)count,neutrophils(NEU)count,and the levels of fibrinogen(Fib),IL-6,and TNF-αwere detected at admission,1 week,2 weeks and 4 weeks after stroke onset,and NIHSS scores were performed at the same time.mRS score was performed at 4 weeks after stroke onset.According to NIHSS score at admission,the patients were divided into two groups:mild stroke(NIHSS 0-4 points)and moderate stroke(NIHSS 5-15 points).The levels of inflammatory factors within 4 weeks were compared between the two groups.The correlation between WBC,NEU counts,the level of Fib and NIHSS score at the same time,and the correlation between WBC,NEU counts and the level of Fib at admission and neurological function restoration during follow-up(NIHSS score at 1 week,2 weeks and 4 weeks,and mRS at 4 weeks)were analyzed.Results A total of 61 patients were enrolled in the study,including 50 in mild stroke group and 11 in moderate stroke group.WBC count[(8.87±2.99)×10^(9)/L vs(7.07±2.06)×10^(9)/L,P=0.019],NEU count[(6.38±2.77)×10^(9)/L vs(4.72±1.66)×10^(9)/L,P=0.010]and the level of Fib[3.31(2.74-4.24)vs 2.71(2.36-3.30),P=0.041]in moderate stroke group at admission were higher than those in mild stroke group.At 1 week after onset,WBC count[(8.80±1.47)×10^(9)/L vs(6.99±2.32)×10^(9)/L,P=0.032],NEU count[(6.16±1.09)×10^(9)/L vs(4.72±2.14)×10^(9)/L,P=0.049]and the level of Fib[3.73(2.92-4.39)vs 2.65(2.25-3.11),P=0.022]in moderate stroke group were higher than those in mild stroke group.At 2 weeks after onset,WBC count[(8.40±1.68)×10^(9)/L vs(6.89±1.28)×10^(9)/L,P=0.012],NEU count[(5.76±1.46)×10^(9)/L vs(4.59±1.12)×10^(9)/L,P=0.024]in moderate stroke group were still higher than that in mild stroke group,but there was no statistical difference in the level of Fib between the two groups.There were no statistical differences in WBC count,NEU count and the level of Fib between the two groups at 4 weeks.There were no statistical differences in the levels of IL-6 and TNF-αbetween the two groups at each time point.The NIHSS score was positively correlated with the level of Fib at admission(r=0.225,P=0.048),1 week(r=0.413,P=0.005)and 2 weeks after onset(r=0.382,P=0.034).The NIHSS score was positively correlated with NEU count at admission(r=0.257,P=0.046)and 2 weeks after onset(r=0.396,P=0.027).The NIHSS score was positively correlated with WBC count at 2 weeks after onset(r=0.451,P=0.011).WBC count at admission was positively correlated with NIHSS score at 2 weeks(r=0.442,P=0.007)and 4 weeks(r=0.518,P=0.011);NEU count at admission was positively correlated with NIHSS score at 1 week(r=0.268,P=0.048),2 weeks(r=0.402,P=0.015)and 4 weeks(r=0.431,P=0.040);the level of Fib at admission was positively correlated with NIHSS score at 1 week(r=0.318,P=0.023)and 2 weeks(r=0.378,P=0.025).Conclusions For mild to moderate ischemic stroke due to large vessel atherosclerosis,the severity of neurological deficit within 2 weeks after onset is positively correlated with the levels of Fib and NEU.The levels of WBC,NEU and Fib in moderate ischemic stroke were higher than those in mild ischemic stroke within 2 weeks after onset,and these differences gradually disappeared at 4 weeks after onset.