急性脑梗死患者血清死亡蛋白激酶1（DAPK1）与N-甲基-D-天门冬氨酸盐（NMDA）受体相关性的研究

摘要

目的：联合应用抗血小板聚集（拜阿司匹林片）、和（或）抗凝（法安明）、和（或）降脂（辛伐他汀）和（或）溶栓（rt-PA）治疗急性脑梗死，同时观察血清死亡蛋白激酶1（death-associated protein kinase1，DAPK1）含量的变化，进一步探讨 NMDA 受体和死亡蛋白激酶（DAPK1）在脑梗死的相互作用，为缺血性脑血管疾病的防治提供临床依据。方法选择发病在72h 以内住院急性脑梗死患者，分为溶栓组11例、常规治疗组56例，并选择我科因后循环缺血住院患者46例做为对照组。溶栓组除了给予 rt-PA 溶栓外，与常规治疗组均联合应用抗血小板聚集（阿司匹林肠溶片100mgqd）、和（或）抗凝（低分子肝素5000u 皮下注射，每日2次）、和（或）降脂（辛伐他汀片20mgqN）及活血化瘀（奥扎格雷钠40mgqd）、清除自由基（依达拉奉30mg bid）等治疗，对照组仅给予常规的活血化瘀、营养神经等治疗，观察治疗前和治疗10d 后患者的血清死亡蛋白激酶1（DAPK1）含量的变化，以及肝功能、血小板、凝血机制及临床神经功能缺损评分进行评定，进一步探讨 NMDA 受体和死亡蛋白激酶1（DAPK1）在缺血性脑血管疾病的相互作用机制。结果溶栓组及常规治疗组患者的死亡蛋白激酶1（DAPK1）含量均高于对照组，治疗10天后溶栓组及常规治疗组患者的死亡蛋白激酶1（DAPK1）含量均降低，常规治疗组更明显（P ＜0.05），溶栓组的神经功能缺损评分（NIHSS）明显降低（P ＜0.05），临床疗效明显优于常规治疗组（P ＜0.05），肝功能、血小板、凝血功能、血脂的指标均在正常范围内。结论死亡蛋白激酶1（DAPK1）通过与 NMDA 受体的 NR2B 亚型结合激活神经细胞死亡通路，激发神经细胞死亡，形成卒中[2]，为缺血性脑血管病的防治提供临床依据。%Objective To investigate changes in the serum level of DAPK1 and its interaction with NMDA receptor in acute cerebral infraction patients, who were treated combined with the anti-platelet aggregation(Aspirin tablets), and/or anticoagulant(Fragmin), and/or lipid-lowering(simvastatin) and/or thrombolysis(rt-PA). Aim to provide clinical evidence for the prevention and treatment of ischemic cerebrovascular disease. Methods 67 patients hospitalized for acute cerebral infarction in 72 hours, were divided into two groups:11 cases with thrombolysis treatment and 56 cases with conventional treatment.46 cases with posterior circulation ischemic were selected as control group. Conventional treatment group was given anti-platelet aggregation(aspirin tablets 100 mg qd), and/or anticoagulation(heparin 5000u subcutaneous injection, bid), anti-oxidant(edaravone 30mg bid), and/or lipid-lowering(simvastatin tablets 20mg qn)and blood stasis transforming(ozagrel 40mg qd) treatment. Rt-PA was added in thrombolysis treatment group and the control group was given conventional blood stasis transforming and nerve nutrition treatments. The serum level of DAPK1, liver function, platelet, coagulation and NIHSS were measured before and after 10-day therapy respectively. The interaction mechanism of NMDA receptor and DAPK1 in ischemic cerebrovascular disease was further explored. Results The serum levels of DAPK1 in the thrombolysis treatment group and the conventional treatment group was higher than the ones in the control group. The serum levels of DAPK1 was lower in the thrombolysis treatment group and the conventional treatment group 10 days later, especially in conventional treatment group(P<0.05); NIHSS was significantly reduced in thrombolysis group(P<0.05). Liver function, platelet, coagulation, blood lipids were within the normal range. Conclusions The interaction of DAPK1 and NR2B subtype of NMDA receptor may activate the pathways of neuronal cell death and induced stroke.Our study will provide the clinical basis for the prevention and treatment of ischemic cerebrovascular disease.