【作者】 许刚；

【导师】 方琪；

【作者基本信息】 苏州大学 ， 神经病学， 2014， 硕士

【摘要】 目的本研究通过前瞻性临床随机对照试验（RCT），评价银杏酮酯分散片联合阿司匹林在缺血性脑卒中治疗和二级预防中的有效性和安全性。方法选择2011年8月至2013年12月在苏州大学附属第一医院神经内科住院的急性缺血性脑卒中患者80例，均为发病5天之内，患者按照随机数字表随机分配至银杏酮酯分散片联合阿司匹林治疗组和阿司匹林对照组。所有病例详细收集临床资料，包括性别、年龄、既往史（高血压病、糖尿病、血脂异常、心脏病、脑梗塞病史等）、治疗史、过敏史，吸烟及饮酒史，所有病例住院后均行心电图、血常规、尿常规、粪便常规、生化全套、头颅影像学检查。并分别在患者入组时、第2周、第4周、第12周及第24周行美国国立卫生院神经功能缺损评分（NIHSS评分），简易精神状态评价量表(MMSE评分)；在入组时、第2周及第12周行血小板聚集率测定；入组时行卒中风险评分量表（ESSEN评分），并观察24周内治疗组及对照组缺血性脑卒中复发率；第2周、第4周、第12周及第24周行肝功能、肾功能、血脂分析检查，应用SPSS13.0软件进行统计学分析。结果1、疗方法不同分为实验组和对照组各40例。银杏酮酯分散片联合阿司匹林治疗组完成有效病例39例，男女比例26／14，年龄(65．55±6．10)岁。阿司匹林空白对照组完成有效病例39例，男女比例28／12，年龄(68．65±7．15)岁。梗死部位：基底节梗死40例、脑干梗死8例、脑叶梗死22例、多发性脑梗死10例。合并高血压病68例，２型糖尿病45例，冠心病１3例。两组患者在年龄、性别、合并疾病方面比较均无统计学差异（P>0.05）。试验组组分别有1例合并肺癌剔除、对照组1例16周出现终点事件（卒中复发）。2、银杏酮酯分散片和空白治疗组急性期NIHSS基线评分分别12.81±4.81(分)和13.01±2.08(分)，差异无明统计学意义；银杏酮酯分散片治疗组和对照组在两周（v1），NIHSS评分差异之间分别为7.57±2.23(分)和8.94±2.81(分),差异均有统计学意义（p<0.05），而在四周（v2）、三个月（v3）、六个月（v4）HIHSS评分变化差异无明显统计学意义。3、银杏酮酯分散片治疗组及空白对照组MMSE评分基线分别为15.7±3.3(分)和15.5±3.1(分)，差异无统计学意义（p<0.05）；银杏酮酯分散片治疗组及对照组在2周、4周、12周时MMSE评分分别为15.9±3.2(分),15.8±3.3(分)，16.8±4.3(分)和16.5±4.6(分)，17.6±4.5(分)和17.3±4.2(分),差异无统计学意义，但在24周时治疗组同对照组评分分别为24.5±4.6(分)和20.4±4.3(分),差异有统计学意义（p<0.05）。4、银杏酮酯分散片治疗组和空白对照组，花生四烯酸及PAF诱导的血小板聚集率在基线水平无明显统计学差异（P>0.05),花生四烯酸诱导的血小板聚集率在第2周和第12周分别为治疗组0.374±0.263%和0.325±0.239%，空白对照组分别为0.374±0.263%和0.501±0.260%，但治疗组同空白对照组之间比较，两组之间差异无明显统计学意义;PAF诱导的血小板聚集率在第2周和第12周，治疗组为0.452±0.220%和0.332±0.215%，对照组为0.416±0.262%和0.477±0.198%,两组之间有明显统计学差异（p<0.05）。5、银杏酮酯分散片联合阿司匹林治疗组及阿司匹林空白对照组ESSEN评分基线分别为3.6±1.1(分)和3.5±1.2(分)，差异无统计学意义（P>0.05）；治疗组和空白组六个月内卒中复发率分别为0%和0.25%，差异有统计学意义（P<0.05）结论1、银杏酮酯分散片联合阿司匹林治疗组治疗急性期缺血性脑卒中NIHSS评分改善优于单纯使用阿司匹林空白对照组，说明银杏酮酯分散片可以改善急性缺血性脑卒中患者神经功能缺损症状。但长期使用神经缺损功能改善不明显。2、银杏酮酯分散片治疗组在第24周时MMSE评分改善明显优于单纯阿司匹林治疗组，说明银杏酮酯分散片能够改善认知功能，对于改善血管性痴呆有治疗效果。3、银杏酮酯分散片在体内可以通过抑制PAF途径的血小板聚集，达到治疗缺血性脑卒中以及脑卒中二级预防的作用。4、银杏酮酯分散片联合阿司匹林治疗组与单纯阿司匹林对照组相比，24周内缺血性脑卒中复发率降低，说明银杏酮酯分散片能够预防脑卒中复发，对缺血性脑卒中有二级预防作用。更多还原

【Abstract】 ObjectiveTo evaluate the validity and security of ginkgo biloba combined with aspirin in thetreatment and secondary prevention for the acute ischemic stroke patients through theclinical random control test.Method80cases with acute ischemic stroke were selected at the in-patient,Department ofNeurology,the First Affiliated Hospital of Soochow University,from October2011toDecember2013.All of them were in five days from onset. The patients were enrolled anddivided randomly into ginkgo biloba test group and aspirin control roup.Clinical data indetail was collected among all cases,including gender,age, anamnesis,(hypertension,diabetes, dislipidemia,heart disease,ischemic stroke and so on), history oftreatment,hypersensitivity,history of smoking and drinking.All patients underwent ECG,blood test, urinalysis, dejecta analysis, blood chemistry test, image test of head. HIHSSand MMSE values were underwent on the2week,4week,12week and24week for thepatient. The rate of the blood platelet aggregation were tested on the onset,2week and12week. The ESSEN value were underwent and the rates of ischemic stroke recrudescencewere accorded for the two group. Function of hepatia and kidney,level of lipidemia weretested on2week,12week,24week for all the patients. SPSS13.0software was used forstatistical analysis.Result1.1.The treatment group and the control group all included40patients according tothe method of the treatment.There are39patients finishing the study for the group of theginkgo biloba combined with aspirin,which include26males and14females, aged (65.55±6.10).39patients for the aspirin control group finished the study,which included28males and11females,aged(68．65±7．15). The infarction part of the brain：40cases forbasal ganglia infarction,8cases for brain stem infarction,20cases for the brain lobeinfarction,10cases for multiple infarction.68cases combined with hypertension,45casescombined with diabetes.13cases combined with coronary heart disease.There is nostatistical difference for gender,age,incorporative diseases for the two groups(p>0.05).Onepatient of the treatment group was excluded for the cancer of lung.Ischmic strokehappened again for one patient of the control group on16weeks.2. The baseline NIHSS values for the ginkgo biloba treatment group was12.81±4.81for the acute ischemic stroke patient, and13.01±2.08for the aspirin control group.There is no statistical difference significantly for the two group(P>0.05). The NIHSSvalue for the ginkgo biloba group were7.57±2.23on2week，and8.94±2.81for thecontrol group. The difference for the two group is statistical significant(p<0.05). But on the4week,12week and24week the differences of the NIHSS value for the two groups areno-statistical significance.3. The baseline MMSE values for the ginkgo biloba treatment group was15.7±3.3,and15.5±3.1for the aspirin control group. There is no statistical differencesignificantly for the two group(P>0.05). The MMSE values for the ginkgo biloba groupwere15.9±3.2,15.8±3.3and16.8±4.3on2week,4week and12weeks separately,soon as16.5±4.6,17.6±4.5and17.3±4.2for the control group. The differences for the twogroup is no-statistical significance(p>0.05).While The MMSE value for the ginkgo bilobagroup were24.5±4.6on24week,so on as20.4±4.3for the control group. The differencefor the two group is statistical significant(p<0.05).4. The baseline rate differences of blood platelet aggregation for the ginkgo bilobatreatment group and for the aspirin control group,are not statistical significantly(P>0.05).The rate of blood platelet aggregation which AA reduced for the ginkgo biloba group were0.374±0.263and0.325±0.239on2week and12weeks separately,so on as0.374±0.263and0.501±0.260for the control group. The differences for the twogroup is no-statistical significance(p>0.05).While the difference is statistical significant for rate of blood platelet aggregation whicn PAF reduced(p<0.05). for the ginkgo biloba groupthe rate is0.452±0.220and0.332±0.215,while0.416±0.262and0.477±0.198separatelyfor the control group.5. The baseline ESSEN values for the ginkgo biloba treatment group was3.6±1.1,and3.5±1.2for the aspirin control group. There is no statistical difference significantly forthe two group(P>0.05). The rate of ischemic stroke recrudescence is0%for the treatmentgroup,0.25%for the control group in24weeks. The difference is significantstatistically (p<0.05).Conclusion1.The NIHSS value of group ginkgo biloba combined with aspirin is lower than thecontrol group significantly in the acute ischemic stroke patients. The result review thatginkgo biloba is benefit for the ischemic stroke patients in acute period of the disease.But there is no significant difference between the test group and the control group in thelong term.2.The MMSE value of the test group is higher than the control group significantly in24weeks,which reveal that ginkgo could improve the cognitive function in the ischemicstroke patients, and be good for VD.3.The gingko biloba could inhibit the planet aggregation through blocking on the PAFand ADP pathway in vivo,which is important for the secondary prevention of the ischemiccerebrovascular diseases.4.The recurrence rate of the test group is lower than the control group in24weeks,which show that ginkgo biloba could reduce the recurrence of the ischemic strokeand be propitious to secondary prevention.更多还原