【作者】 吴硕琳；

【导师】 刘瑞珍；

【作者基本信息】 山西医科大学 ， 神经病学， 2011， 硕士

【摘要】 目的：丁苯酞被《中国脑血管病防治指南2010》推荐为在脑梗死急性期使用药物之一。轻度认知功能障碍是介于正常老龄化和痴呆或阿尔兹海默病之间过渡阶段。多发腔隙性脑梗死（MLI）常可合并轻度认知功能障碍（MCI）存在，但这类人群往往容易被忽略。蒙特利尔认知评估量表为目前公认的MCI筛查工具，超氧化物歧化酶(SOD)是体内自由基清除系统，具有脑保护作用，在急性脑梗死中其水平是降低的。本次研究运用口服丁苯酞对新发急性腔隙性脑梗死中存在轻度认知功能异常患者进行治疗8周观察其评分有无改善，同时测定血清SOD水平变化情况，旨在观察丁苯酞对新发急性腔隙性脑梗死合并轻度认知功能障碍这部分患者的治疗效果（包括认知功能改善及对血清SOD活性的影响）及提供可能的作用机制，并探讨该药在干预早期认知功能损害方面的作用和意义。方法：制定严格纳组标准后，收集新发急性腔隙性脑梗死合并轻度认知功能障碍40例，经患者知情同意，随机分组丁苯酞治疗组（20例，给予口服丁苯酞0.2一日三次）及常规治疗组（20例，口服吡拉西坦常规治疗），随访8周，用蒙特利尔认知评估认知量表对患者进行再次评分。所有患者在治疗前、治疗后第8周于清晨采取空腹肘静脉血4.0ml,分离血清,低温(-20℃)保存待检，ELISA法测定血清SOD活性。结果：1.蒙特利尔量表评分对比：1.1丁苯酞治疗组治疗前后比较差异有统计学意义；1.2常规治疗组治疗前后比较差异有统计学意义（P<0.05），提示进行常规治疗，患者认知功能水平下降可能性仍然很大；1.3丁苯酞治疗组前后差值与常规治疗组前后差值比较，差异具有统计学意义，提示提示在均衡了病情自身发展（时间的因素）、年龄等因素后，丁苯酞对改善腔梗合并轻度认知功能障碍病人的认知水平是有统计学意义的。2.血清SOD活性各组比较: 2.1丁苯酞治疗组治疗前后比较差异有统计学意义（P<0.05）；2.2常规治疗组治疗前后比较差异无统计学意义（P>0.05）；2.3丁苯酞治疗组前后差值与常规治疗组前后差值比较，差异具有统计学意义。结论：1.丁苯酞对于急性新发腔隙性脑梗死合并轻度认知功能障碍患者，可以改善其认知功能。2.丁苯酞能改善患者血清SOD水平，提示该药物对新发脑梗死患者脑内的自由基清除能力提高有帮助，对缺血性脑损伤修复是有意义的。3.经过丁苯酞治疗，个体评分可达到正常水平及以上，2组差异具有统计学意义，提示丁苯酞对于阻止MCI合并多发腔隙性脑梗死的患者进展为痴呆是有治疗意义的，这为丁苯酞作为早期干预痴呆的研究和治疗提供了有力的临床证据。4.鉴于丁苯酞治疗组前后认知评分改善与同期检测的血清SOD活性改变均有统计学意义，提示丁苯酞对轻度认知功能障碍的病人治疗有改善的机制可能与SOD有关。5.鉴于对照组治疗前后血清SOD活性改变与评分变化之间的不一致性，我们推测血清SOD活性与认知功能改善之间为非因果关系,提高血浆SOD水平并非是丁苯酞改善认知功能的唯一机制。更多还原

【Abstract】 Objective: DL-3-n-butylphthalide(NBP)is recommended to use in the acute stroke by theChinese cerebravascular disease therapy guidelines (2010).Mild cognitive impair(MCI) is thestate between the aging and the dementia. multiple lacunar infarction(MLI) usually exists withMCI but often is ignored in clinic. Montreal Cognitive Assessment(MoCA) is acceptedcomprehensively as a tool to screen MCI. Superoxidase dismutase(SOD)is oxygen-derived freeradicals and can protect our neural system while acute stroke happens.The study here aims to useoral NBP to treat patients of acute MLI with MCI for 8 weeks to investigate the impact of NBPon the changes of the assessment scores of MoCA and serum SOD level and explore themechanism of the change ,to discuss the importance and meaning of NBP using in early subtalcognitive impair patients to protect them from dementia.Methods: According to strict joining group standard, 40 patients of acute MLI with MCI areaccepted in this study.After informed the test aim ,giving permission,the patients were allocatedrandomly to two groups,one is NBP treatment group(n=20) ,the other is controlling group usingpiracetam tablets (n=20).after 8 weeks,they were required to take the MoCA again then got thenew scores .All the patients were extracted venous blood (4ml each person in the morning andfasting required)that the serum was separated from as samples.the samples were kept for lowtemperature (20degrees below zero)then sent for SOD evaluation. ELISA method is used.Results:1. MoCA Scores:1.1. The before and after self control study in treatment group:the change has the statisticallymeaning(P<0.05)1.2. The before and after self control study in controlling group:the change has the statisticallymeaning(P<0.05)，suggest high possibility of the level of cognitive impair decreasing whileusing piracetam.1.3. The change between the two groups are tested to be satistically meaningful,that suggestNBP can improve the level of cognitive impair in patients of MLI with MCI besides thefactors such as the natual progress of disease the age and sex ,et.2. Serum SOD Level:2.1 The change between the before and after treatment in NBP group is tested to be statisticallymeaningful (P<0.05) 2.2 The change between the before and after treatment incontrolling group has no meaning instatistics after being tested（P>0.05）.2.3 The after treatment level between the two groups is tested to be statistically meaningful.(P<0.05)Conclusions:1. NBP can ameliorate the CI in patients of acute MLI with MCI2. NBP can improve the level of SOD in these patients,showing its abilityto protect neuralsystem from ischemia injury.3. Some individuals can reach the normal score after treatment with NBP,suggeat that NBP canbe used to early subtal CI to avoid dementia in such patients,and provide the rigid evidenceof using NBP as a method to response to early subtal CI patients from dementia.4. AS is seen that both of the change of MoCA scores and SOD level in NBP group arestatistically meaningful,we conclude that the mechanism of NBP on CI is probablyassociated with serum SOD level .5. AS is seen that the change of MoCA scores in piracetam group is statistically meaningfulwhile the serum SOD is not ,we conclude that SOD level is not the single affecting factor tothe CI level,that is ,to improve the SOD level in patients is not the unique mechanism ofNBP ameliorating the CI level .更多还原