远隔缺血适应对静脉溶栓后急性缺血性脑卒中患者神经功能、脑损伤标志物及血管炎症介质的影响

Effect of remote ischemic conditioning on neurological function,brain injury markers and vascular inflammatory mediators in patients with acute ischemic stroke after intravenous thrombolysis

目的探讨远隔缺血适应(RIC)对急性缺血性脑卒中(AIS)患者静脉溶栓后神经功能、脑损伤标志物及血管炎症介质的影响。方法选择2022年5月至2022年10月郑州大学附属郑州中心医院神经内科收治的90例AIS患者为研究对象,按治疗方法将患者分为RIC组(n=29)、假RIC组(n=30)和对照组(n=31)。3组患者均给予阿替普酶静脉溶栓治疗;溶栓24 h后,RIC组患者给予RIC治疗,假RIC组给予假性RIC治疗,对照组不做RIC治疗;3组患者均治疗14 d。收集3组患者的年龄、性别、吸烟、饮酒、高血压、糖尿病、冠状动脉性心脏病及卒中病史等基本资料;入院24 h内抽取患者空腹外周静脉血4~5 mL,离心取上层血清,检测三酰甘油(TG)、总胆固醇(TC)、糖化血红蛋白(HbA1c)、血肌酐(Scr)水平;应用凝血分析仪检测纤维蛋白原(FIB)与D-二聚体水平。RIC治疗前、治疗7 d、治疗14 d时抽取3组患者外周静脉血4~5 mL,离心取上层血清,采用酶联免疫吸附试验法检测S100钙结合蛋白β(S100β)、脂蛋白相关磷脂酶A2(Lp-PLA2)、白细胞介素-6(IL-6)水平;采用双抗体夹心酶联免疫吸附法检测神经元特异烯醇化酶(NSE)水平。应用美国国立卫生研究院卒中量表(NIHSS)和改良Rankin量表(mRS)评估3组患者神经功能损伤程度。记录3组患者RIC治疗过程中的不良反应情况。结果对照组、假RIC组和RIC组治疗总有效率分别为90.32%(28/31)、90.00%(27/30)和100.00%(29/29),3组患者的治疗总有效率比较差异无统计学意义(χ^(2)=3.059,P>0.05)。对照组、假RIC组和RIC组患者治疗前TG、TC、HbA1c、Scr、FIB和D-二聚体表达水平比较差异无统计学意义(P>0.05)。治疗前,3组患者血清Lp-PLA2、IL-6、S100β、NSE表达水平比较差异无统计学意义(P>0.05)。3组患者治疗7、14 d时血清Lp-PLA2、IL-6、S100β、NSE水平显著低于治疗前(P<0.05)。治疗7、14 d时,RIC组患者的血清Lp-PLA2、IL-6、S100β、NSE水平显著低于假RIC组和对照组(P<0.05),对照组与假RIC组患者的血清Lp-PLA2、IL-6、S100β、NSE水平比较差异无统计学意义(P>0.05)。治疗前,3组患者NIHSS、mRS评分比较差异无统计学意义(P>0.05)。3组患者治疗7、14 d时的NIHSS评分及治疗14、90 d时的mRS评分显著低于治疗前(P<0.05)。RIC组患者治疗14 d时的NIHSS评分及治疗90 d时的mRS评分显著低于假RIC组和对照组(P<0.05);对照组与假RIC组各时间点NIHSS评分和mRS评分比较差异无统计学意义(P>0.05)。RIC组在治疗过程中有2例患者出现上肢疼痛、麻木,暂停治疗后患者不适感觉消失;假RIC组和对照组无不良反应发生。结论静脉溶栓后给予RIC治疗能显著促进AIS患者神经功能恢复,降低血管炎症介质和脑损伤标志物水平,减轻脑损伤。

Objective To investigate the effects of remote ischemic conditioning(RIC)on neurological function,brain injury markers and vascular inflammatory mediators in patients with acute ischemic stroke(AIS)after intravenous thrombolysis.Methods Ninety AIS patients admitted to the Department of Neurology of Zhengzhou Central Hospital Affiliated to Zhengzhou University from May 2022 to October 2022 were selected as the research subjects.The patients were divided into the RIC group(n=29),the pseudo-RIC group(n=30)and the control group(n=31)according to the treatment method.All patients in the three groups were treated with intravenous thrombolysis with alteplase.After 24 hours of thrombolysis,the patients in the RIC group were given RIC treatment,the patients in the pseudo-RIC group were given pseudo-RIC treatment,and the patients in the control group were not given RIC treatment.All patients in the three groups were treated for 14 days.Clinical data of patients in the three groups were collected,including age,gender,and history of smoking,drinking,hypertension,diabetes mellitus,coronary artery disease and stroke.About 4-5 mL of the fasting peripheral venous blood was drawn from the patients within 24 hours after admission to the hospital and was centrifuged to obtain the serum.The levels of triacylglycerol(TG),total cholesterol(TC),glycated hemoglobin(HbA1c)and serum creatinine(Scr)were detected;the levels of fibrinogen(FIB)and D-dimer were detected by using a blood coagulation analyzer.The peripheral venous blood(4-5 mL)was drawn from the patients in the three groups before treatment and on the 7 th and 14 th days of treatment and was centrifuged to obtain the serum.The levels of S100 calcium-binding proteinβ(S100β),lipoprotein-associated phospholipase A2(Lp-PLA2)and interleukin(IL)-6 were detected by using the enzyme-linked immunosorbent assay(ELISA).The neuron specific enolase(NSE)level was detected by using the double antibody sandwich ELISA.The National Institutes of Health Stroke Scale(NIHSS)and the modified Rankin scale(mRS)were used to assess the neurological impairment of patients in the three groups.The adverse reactions during RIC treatment in the three groups were recorded.Results The overall effective rates of patients in the control group,pseudo-RIC group and RIC group were 90.32%(28/31),90.00%(27/30)and 100.00%(29/29),respectively;there was no statistically significant difference in the overall effective rate among the three groups(χ^(2)=3.059,P>0.05).There was no statistically significant difference in the serum TG,TC,HbA1c,Scr,FIB and D-dimer levels of patients among the control group,pseudo-RIC group and RIC group before treatment(P>0.05).Before treatment,there was no statistically significant difference in the serum Lp-PLA2,IL-6,S100βand NSE levels among the three groups(P>0.05).The serum Lp-PLA2,IL-6,S100βand NSE levels of patients on the 7 th and 14 th days of treatment were significantly lower than those before treatment in the three groups(P<0.05).On the 7 th and 14 th days of treatment,the serum Lp-PLA2,IL-6,S100βand NSE levels of patients in the RIC group were significantly lower than those in the pseudo-RIC group and control group(P<0.05),and these indexes showed no statistically significant difference between the control group and the pseudo-RIC group(P>0.05).There was no statistically significant difference in the NIHSS and mRS scores of patients among the three groups before treatment(P>0.05).The NIHSS scores on the 7 th and 14 th days of treatment and the mRS scores on the 14 th,90 th days of treatment of patients were significantly lower than those before treatment in the three groups(P<0.05).The NIHSS score on the 14 th day of treatment and the mRS score on the 90 th day of treatment in the RIC group were significantly lower than those in the pseudo-RIC group and control group(P<0.05);there was no significant difference in the NIHSS and mRS scores between the control group and the pseudo-RIC group at each time points(P>0.05).In the RIC group,2 patients developed upper limb pain and numbness during the treatment,and the symptoms disappeared after the treatment was suspended;no adverse reactions occurred in the pseudo-RIC group and the control group.Conclusion RIC therapy after intravenous thrombolysis can significantly promote neurological recovery,attenuate brain damage,and reduce the expression levels of vascular inflammatory mediators and brain damage markers in patients with AIS.