一种C-Jun N-末端激酶肽抑制剂在沙土鼠全脑缺血中的保护作用

目的 为了进一步研究海马C1区域神经细胞活动中JNK的作用，我们评价了一种JNK抑制剂即D-JNKI1在沙土鼠一过性大脑缺血模型中对迟发性神经细胞死亡（DND）的作用。方法 55只沙土鼠随机分为11个组。5组沙土鼠先接受5min前脑缺血处理，再灌注3h后，通过立体定向方法。向每组沙土鼠右侧侧脑室内分别注入不同浓度的D-JNKI1（2μL PBS内加入0．00012，0．0012，0．012，0．12，1．2μmol／L D-JNKI1，每组n=5）。对照组（n=5）：沙土鼠先接受5min前脑缺血处理，再灌注3h后，通过立体定向方法方法向右侧侧脑室内仅注入PBS2μL。腹腔内注射组（n=5）沙土鼠；先接受5min前脑缺血处理，再灌注3h后，1．2μmol／L D-JNKI1溶于0．5mL PBS腹腔内注射。假手术组（n=5）；沙土鼠仅暴露双侧颈总动脉，未夹闭。预处理组（共3组，n=15）：先将0．0012μmol／L D-JNKI1，0．00012μmol／L D-JNKI1溶于2μL PBS，分别注入两组沙土鼠的右侧侧脑室内，另外一组沙土鼠的右侧侧脑室内仅仅注入PBS2μL，30min后三组均夹闭双侧颈总动脉2min，48h后再次接受双侧颈总动脉夹闭5min。所有沙土鼠从接受夹闭5min双侧颈总动脉后4d处死，作冰冻切片和Niss1染色。结果 缺血再灌注3h后用D-JNKI-1治疗，有神经保护作用，最好的神经保护效应浓度为0．0012μmol／L。D-JNKI-1预处理加强了2min预处理所诱导的缺血耐受效应。结论D-JNKI1在沙土鼠全脑缺血模型中对海马CA1区域的迟发性神经细胞死亡有潜在的神经保护作用。     

侧脑室微量注射左旋多巴治疗大鼠帕金森病

目的观察经侧脑室注射左旋多巴对帕金森病（PD）大鼠的影响。方法应用“羟基多巴胺立体定向脑内注射制备偏侧损毁的PD大鼠模型，并用阿扑吗啡（APO）皮下注射诱发大鼠向健侧旋转。将24只PD大鼠随机分为4组（n=6），经侧脑室注入生理盐水组为对照组，余3组分别经侧脑室注射浓度为0．1μg／μl、1μg／μl和5μg／μl的左旋多巴1μl，4μl／d，连续1周；观察在注射后不同时间大鼠旋转行为以及中脑黑质多巴胺能神经元数量的变化。结果经侧脑室注射1μg/μl和5μg/μl的左旋多巴后。与对照组相比，PD大鼠向健侧的旋转圈数明显减少（P〈0．01），左旋多巴效果在2h左右达到高峰，且中脑黑质多巴胺能神经元的数量也明显增多（P〈0．01）。结论经侧脑室注射适当剂量的左旋多巴可有效地改善PD大鼠的旋转行为，并增加中脑黑质多巴胺能神经元数量。     

精氨酸加压素对大鼠脑水肿形成及水孔蛋白-4表达的影响

目的 探讨精氨酸加压素(AVP)对大鼠脑水肿形成和水孔蛋白-4(AQP4)表达的影响.方法 90只SD大鼠随机分为正常对照组、假手术6 h、1 d、3 d、5 d组及AVP6 h、1 d、3 d、5 d组.于大鼠侧脑室注射AVP后,分别于相应时间点对脑室周围组织进行脑含水量测定,免疫组化技术检测脑室周围组织AQP4的表达.结果 假手术组与正常对照组脑组织含水量及AQP4表达未见增加.AVP组大鼠侧脑室注射AVP 6 h脑室周围脑组织含水量开始增加,1 d即达高峰,与正常对照组比较差异有统计学意义(均P＜0.01),5 d降到基础水平;脑室周围AQP4表达亦在注射AVP 6 h开始增加,1 d即达高峰,与正常对照组比较差异有统计学意义(均P＜0.01),第5 d恢复到基础水平,与脑水肿的变化相一致.结论 AVP可上调AQP4表达,引起大鼠脑含水量增加,导致脑水肿的发生.     

白细胞介素-6对大鼠脑缺血保护作用的实验研究

目的 探讨白细胞介素-6（IL-6）对大鼠脑缺血的保护作用。方法 将75只SD大鼠随机分为3组（n=25），采用线栓法制作大鼠脑缺血模型，手术一组：侧脑室注射IL-6 0．5μg，注射速度为15μg/h；手术二组：鼠尾静脉注射IL-6 0．5μg，注射速度为15μg/h；对照组：侧脑室注射等体积生理盐水。术后对大鼠进行神经症状评分及测量各组大鼠脑梗塞范围。结果 70只大鼠进入结果分析。分析指标：（1）脑梗塞范围：手术一组和手术二组较对照组明显减小（P〈0．01），分别减少（24±3）％和（22±3．5）％，提示神经功能缺损明显减轻。（2）神经症状评分：手术一组和手术二组较对照组明显降低（P〈0．01）．提示神经功能障碍明显减轻。结论 IL-6对大鼠脑缺血有明显的神经保护作用。     

阿尔茨海默病与血管性痴呆患者血浆同型半胱氨酸与超氧化物歧化酶的比较

目的探讨血浆同型半胱氨酸（Hcy）水平与超氧化物歧化酶（SOD）浓度和阿尔茨海默病（AD）与血管性痴呆（VaD）患者认知功能损害之间的关系。方法将入组病例分成AD组和VaD组，分别测定血浆Hcy、SOD水平并进行比较；采用简易智能状态量表（MMSE）评定认知功能水平。结果AD组Hcy浓度为（16．24±6．62）μmol／L，VaD组为（25．81±11．81）μmol／L，两组比较差异有统计学意义（P〈0．01）。AD组SOD浓度为（165．94±35．92）μmol／L，VaD组为（167．76±29．86）μmol／L，两组比较差异无统计学意义（P〉0．05）。AD组Hcy浓度与SOD水平呈负相关（r=-0．346，P〈0．05），VaD组SOD水平与年龄呈负相关（r=-0．358，P〈0．05），两组患者的MMSE评分与Hcy浓度呈负相关（r=-0．263，P〈0．01）。结论血浆Hcy、SOD水平可能是预测认知功能损害程度的一个重要生化指标。     

阿司匹林和阿托伐他汀对心房颤动患者血浆溶血磷脂类含量和卒中发生率的影响

目的：观察非瓣膜性心房颤动（NVAF）患者经阿司匹林和（或）阿托伐他汀干预后血浆溶血磷脂类分子（LPA／AP）含量的变化。方法：测定169例NVAF患者血浆溶血磷脂酸（LPA）及其相似总磷脂（AP）含量，并与124例正常对照者进行比较。169例NVAF患者随机分为NVAF对照组（n=52）、阿司匹林组（n=61）和阿司匹林＋阿托伐他汀组（n=56），NVAF对照组不予任何处理，阿司匹林组予阿司匹林（100mg／d），阿司匹林加阿托伐他汀组予阿司匹林（100mg／d）和阿托伐他汀（10mg／d）。检测三组患者治疗前和治疗后3个月和1年时的血浆LPA／AP含量，观察3个月和1年时各组卒中发生情况。结果：NVAF患者血浆LPA及AP含量分别为（3．56±0．42）μmol／L和（6．12±0．57）U，显著高于正常对照者的（2．65±0．44）μmol／L和（4．68±0．45）U（P均〈0．01）。治疗前、治疗后3个月和1年时，NVAF对照组血浆LPA含量分别为（3．61±0．49）、（3．52±0．51）和（3．66±0．59）μmol／L，AP分别为（6．23±0．59）、（6．47±0．61）和（6．36±0．79）U，无显著差异；阿司匹林组LPA分别为（3．53±0．46）、（3．12±0．62）和（2．94±0．60）μmol／L，AP分别为（6．37±0．66）、（5．64±0．52）和（5．33±0．61）U，治疗后LPA和AP均较治疗前显著下降（P〈0．01）；阿司匹林＋阿托伐他汀组LPA分别为（3．59±0．33）、（2．58±0．50）和（2．46±0．48）μmol／L，AP分别为（6．19±0．53）、（4．98±0．50）和（4．64±0．58）U，治疗后LPA和AP均较治疗前显著下降（P〈0．01），且较阿司匹林组下降更显著（P〈0．01）。NVAF对照组、阿司匹林治疗组和阿司匹林＋阿托伐他汀组3个月卒中发病例数分别为7、6和3例，1年时分别为16、11和6例，阿司匹林组和阿司匹林＋阿托伐他汀组显著少于NVAF对照组（P〈0．01），阿司匹林＋?     

头孢曲松钠对大鼠蛛网膜下腔出血后认知功能的影响

目的 探讨头孢曲松钠（CEF）对大鼠蛛网膜下腔出血（SAH）后的认知功能的影响及其机制。方法 将68只成年SD大鼠随机分为4组:正常组（n=12）、对照组（n=24）、CEF低剂量治疗组（n=8）和CEF高剂量治疗组（n=24）。采用枕大池双次注血方法建立大鼠SAH模型。SAH后3 h经小脑延髓池缓慢注射100 μl CEF（高剂量组浓度为100 μmol/L,低剂量组浓度为50 μmol/L）,对照治疗组注射等体积生理盐水。采用Morris水迷宫检测各组动物学习记忆能力;Western blot检测各组大鼠海马 Caspase-3和兴奋性氨基酸转运体2（EAAT2）的表达水平。结果 与对照组相比,CEF治疗组SAH后动物的水迷宫实验中的逃逸时间显著减少（P<0.05）,大鼠海马组织中EAAT2的表达增加（P<0.05）,Caspase-3的表达减少（P<0.05）。结论 CEF对SAH后具有显著的神经保护作用,CEF治疗可能通过上调星形胶质细胞EAAT2的表达逆转SAH诱导的神经损伤。     

高渗刺激引起培养的大鼠下丘脑星形胶质细胞和C6细胞合成并释放谷氨酸

目的观察高渗刺激对培养的大鼠下丘脑星形胶质细胞或C6细胞合成、释放谷氨酸的影响。方法获取一日龄SD大鼠下丘脑组织，进行星形胶质细胞培养、纯化和鉴定。培养细胞随机分五组：（1）等渗组：用新鲜等渗培养液置换原先的培养液，将细胞分成5个亚组，分别孵育1、3、5、10和15min。（2）高渗组：用320mosMNaCl高渗溶液置换原先的培养液，将细胞分成5个亚组，分别孵育1、3、5、10和15min。（3）甘伯酸（carbenoxolone，CBX，一种缝隙连接阻断剂）＋等渗组和（4）CBX＋高渗组：用含有CBX（终浓度为100mmol／L）的等渗培养液作用1h，后分别用等渗或高渗培养液置换出原培养液，将细胞分成5个亚组，分别孵育1、3、5、10和15min。（5）Ca2＋高渗组：用含有Ca2＋（1000μmol／L）的等渗培养液作用1h，后用高渗培养液置换出原培养液，将细胞分成5个亚组，分别孵育1、3、5、10和15min。每个亚组5个培养皿。收集各组的细胞，进行抗谷氨酸和抗胶质原纤维酸性蛋白（Glial fibrillary acidic protein，GFAP）的双重免疫荧光染色，Confocal显微镜观察。用反相高效液相色谱荧光测定法测定细胞培养液中谷氨酸的含量。培养的C6细胞分为四组：等渗组，高渗组，CBX＋等渗组和CBX＋高渗组，用于流式细胞仪（flowcytometry，FCM）定量检测细胞内谷氨酸的含量。结果星形胶质细胞内抗GFAP染色的荧光强度在五组问无明显差异。星形胶质细胞内抗谷氨酸染色的荧光强度在等渗组中各时间点无明显变化，高渗组中在刺激1min后表达增加，5min达到高峰，15min恢复到正常。CBX＋高渗组的抗谷氨酸染色荧光强度明显高于CBX＋等渗组和等渗组，一直维持到15min不下降。培养基中的谷氨酸浓度在等渗组各时间点无明显变化，高渗组中谷氨酸浓度从5min到15min明显增加。Ca2＋高渗组和CBX＋高渗组中?     

重症脑卒中患者并发高渗血症的危险因素

目的探讨重症脑卒中患者并发高渗血症的危险因素，为制定干预措施提供依据。方法重症脑卒中患者80例，根据评价生存与死亡的血浆渗透压界值分为高渗组（〉310mmol／L，34例）和非高渗组（≤310mmol／L，46例）。监测可能影响血浆渗透压的危险因素。结果大剂量甘露醇（〉100g／d）、高钠血症和高血糖症是导致高渗血症的3个主要危险因素。高渗组4周生存率（47．1％）明显低于非高渗组（78．3％），两组比较差异有统计学意义（P〈0．01）。结论引起高渗血症的主要危险因素是大剂量甘露醇、高钠血症和高血糖症，高渗血症患者预后差，生存率低。     

吸烟对男性精神分裂症患者临床症状的影响及可能机制

目的探讨吸烟对男性精神分裂症患者临床症状的影响及氧化应激在精神分裂症高吸烟率中的作用。方法研究共入组男性精神分裂症患者130例,根据目前的吸烟状况分吸烟组（74例）和非吸烟组（56侧）,运用阳性和阴性症状量表（PANSS）评定精神病理症状;采用分光光度法检测其血浆超氧化物岐化酶（SOD）、过氧化氢酶（CAT）活性以及丙二醛（MDA）浓度。结果（1）吸烟组PANSS阳性症状（14．5±6．3）分显著低于非吸烟组（17．5±4．9）分（P〈0．05）;吸烟组患者吸烟数量与PANSS阴性症状分显著负相关（r=-0．23,P=0．02）。（2）血浆CAT活性吸烟组（2．9±0．3）×10^3U／L显著高于非吸烟组（1．6±0．2）×10^3U／L,吸烟患者血浆SOD活性与吸烟数量显著相关（r=0．24,P=0．04）;血浆MDA浓度吸烟组（9．2±0．7）mmol／L显著低于非吸烟7组（14．4±1．7）mmol／L。结论男性精神分裂症患者的吸烟可能通过缓解氧化应激来改善部分精神病理症状。     

Effects of genistein on neuronal apoptosis, and expression of Bcl-2 and Bax proteins in the hippocampus of ovariectomized rats

Genistein is one of several isoflavones that has a structure similar to 17β-estradiol, has a strong antioxidant effect, and a high affinity to estrogen receptors. At 15 weeks after ovariectomy, the expression of Bcl-2 in the hippocampus of rats decreased and Bax expression increased, with an obvious upregulation of apoptosis. However, intraperitoneal injection of genistein or 17β-estradiol for 15 consecutive weeks from the second day after operation upregulated Bcl-2 protein expression downregulated Bax protein expression, and attenuated hippocampal neuron apoptosis. Our experimental findings indicate that long-term intervention with genistein can lead to a decrease in apoptosis in hippocampal neurons following ovariectomy, upregulate the expression of Bcl-2, and downregulate the expression of Bax. In addition, genistein and 17β-estradiol play equal anti-apoptotic and neuroprotective roles.     

Ultrastructure of non-myelinated neurons during energy deprivation

Summary This paper examines the neuropathology of oxygen-glucose deprivation uncomplicated by stagnant conditions. Rabbit vagus nerves were pulled into asmulti-compartment perfusion chamber, stimulated five times per second and deprived of energy by substituting nitrogen and deoxyglucose for oxygen and glucose in the Locke's perfusate. After incubation the compartments were perfused with gluteraldehyde solution, and the nerves were prepared for electron microscopy. Fixation in the compartments ensured precise cross and longitudinal sections which permitted quantitative comparisons. Although the action potentials ceased in 45 min, 1 h of energy deprivation did not significantly affect the ultrastructure. After 2 h of deprivation the axons were smaller and flattened and microtubules appeared packed together. In the smallest axons the microtubules were gone, the neurofilaments were compacted and the few mitochondria had a dense, homogenous appearance. By 4 h the shrinking was extreme, yet 8% were swollen much larger than any of the controls. Longitudinal views showed these balloned areas were greatly expanded regions of the smallest axons. Both tiny and huge regions were devoid of microtubules and the swollen axons contained expanded mitochondria.Calcium is indirectly implicated in the pathogenesis by the concurrence of mitochondrial alteration as the microtubules disappear coupled with the known role of mitochondria in calcium regulation and the reported effect of high calcium on microtubual dissociation. In is suggested that axons first shrink as osmotially active molecules are used or washed out. After a time without energy the mitochondria can no longer regulate the intracellular calcium, microtubules dissociate, and calcium-activated phospholipases create osmotically active molecules. Finally, high-amplitude, disruptive swelling occurs.Supported, in part, by a Grant-in-aid from the American Heart Association with funds contributed by the American Heart Association, Kansas Affiliate and by the University of Kansas Biomedical Sciences Support Grant RR0737     

星形胶质细胞对天冬氨酸特异性半胱氨酸蛋白酶介导β淀粉样蛋白早期突触毒性作用的影响

目的探讨星形胶质细胞(astrocyte,AS)对天冬氨酸特异性半胱氨酸蛋白酶(cysteinyl aspartate specific proteinase,caspase)介导β淀粉样蛋白(β-amyloid,Aβ)早期突触毒性作用的影响,以期为进一步研究与血管性痴呆(vascular dementia,Va D)的发病机制奠定基础。方法以原代培养大鼠海马纯神经元体系(NE-S)及混合培养体系(MIX-S,主要包含神经元及AS)为研究对象,各体系分为6组:对照组、caspase-8抑制剂组、caspase-9抑制剂组、Aβ处理组、caspase-8抑制剂预处理加Aβ组和caspase-9抑制剂预处理加Aβ组。免疫荧光检测各组近胞体10μm段树突中突触后密度蛋白(postsynaptic density-95,PSD95)表达量的变化。结果 1在NE-S与MIX-S中,与对照组相比,caspase-8抑制剂组、caspase-9抑制剂组PSD95的表达量均无明显差异,Aβ处理组PSD95的表达量均显著降低(P均0.001)。2在NE-S中,与Aβ处理组相比,caspase-9抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,caspase-8抑制剂预处理加Aβ组则无显著改变;在MIX-S中的结果则相反,即caspase-8抑制剂预处理加Aβ组PSD95的表达量显著回升至对照组水平,而caspase-9抑制剂预处理加Aβ组则无显著改变。3MIX-S与NE-S两种培养系统间相比较,对照组间及Aβ处理组间PSD95的表达量均无显著差异,而caspase-8抑制剂预处理加Aβ组间及caspase-9抑制剂预处理加Aβ组间PSD95的表达量差异有显著性。结论在Aβ早期突触毒性作用中,AS参与caspase-8介导的死亡受体通路激活过程,且参与抑制神经元的线粒体通路。     

Development of 18F-labeled radiotracers for neuroreceptor imaging with positron emission tomography

Positron emission tomography (PET) is an in vivo molecular imaging tool which is widely used in nuclear medicine for early diagnosis and treatment follow-up of many brain diseases. PET uses biomolecules as probes which are labeled with radionuclides of short half-lives, synthesized prior to the imaging studies. These probes are called radiotracers. Fluorine-18 is a radionuclide routinely used in the radiolabeling of neuroreceptor ligands for PET because of its favorable half-life of 109.8 min. The delivery of such radiotracers into the brain provides images of transport, metabolic, and neurotransmission processes on the molecular level. After a short introduction into the principles of PET, this review mainly focuses on the strategy of radiotracer development bridging from basic science to biomedical application. Successful radiotracer design as described here provides molecular probes which not only are useful for imaging of human brain diseases, but also allow molecular neuroreceptor imaging studies in various small-animal models of disease, including genetically-engineered animals. Furthermore, they provide a powerful tool for in vivo pharmacology during the process of pre-clinical drug development to identify new drug targets, to investigate pathophysiology, to discover potential drug candidates, and to evaluate the pharmacokinetics and pharmacodynamics of drugs in vivo.     

Differential expression of carboxyl terminal derivatives of amyloid precursor protein among cell lines.

Understanding the pathway for amyloid percursor protein (APP) catabolism has become an important line of investigation. APP is a ubiquitous membrane bound protein that is rapidly cleaved at the membrane, yielding a secreted protein identical to protease nexin II and an internalized 11.5 kDa 100 residue C terminal derivative (CTD). The levels of CTDs in a variety of cell lines have been examined and were found to differ. Cell types associated with the pathology of Alzheimer's disease (AD), such as olfactory neuroblasts (ON) and cortical vascular endothelial cells, have higher levels of CTDs than lymphoblasts and melanoma cells. The mechanism of CTD catabolism appears to involve the lysosome because blockade of lysosomal but not endosomal or mitochondrial function results in increased levels of CTDs. Under these conditions, production of larger, amyloidogenic CTDs is also seen. In cells possessing higher levels of CTDs we find that the mechanism for production of amyloidogenic CTDs may involve the internalization of intact full-length APP. Thus, inhibition of the lysosomal system appears capable of generating amyloidogenic peptides. The amount of amyloidogenic peptides appears to vary among cell lines. Such variation may shed light on why amyloid accumulates around specific cell types such as vascular endothelial cells, neurons, and glia. Finally, disfunction of the lysosomal system may play a role in the pathogenesis of Alzheimer's disease.     

Magnetic resonance morphometry of the loss of gray matter volume in Parkinson’s disease patients

Voxel-based morphometry can be used to quantitatively compare structural differences and functional changes of gray matter in subjects.In the present study,we compared gray matter images of 32 patients with Parkinson’s disease and 25 healthy controls using voxel-based morphometry based on 3.0 T high-field magnetic resonance T1-weighted imaging and clinical neurological scale scores.Results showed that the scores in Mini-Mental State Examination and Montreal Cognitive Assessment were lower in patients compared with controls.In particular,the scores of visuospatial/executive function items in Montreal Cognitive Assessment were significantly reduced,but mean scores of non-motor symptoms significantly increased,in patients with Parkinson’s disease.In addition,gray matter volume was significantly diminished in Parkinson’s disease patients compared with normal controls,including bilateral temporal lobe,bilateral occipital lobe,bilateral parietal lobe,bilateral frontal lobe,bilateral insular lobe,bilateral parahippocampal gyrus,bilateral amygdale,right uncus,and right posterior lobe of the cerebellum.These findings indicate that voxel-based morphometry can accurately and quantitatively assess the loss of gray matter volume in patients with Parkinson’s disease,and provide essential neuroimaging evidence for multisystem pathological mechanisms involved in Parkinson’s disease.     

Neuroprotective role of fibronectin in neuron-glial extrasynaptic transmission

Most hypotheses concerning the mechanisms underlying Parkinson’s disease are based on altered synaptic transmission of the nigrostriatal system.However,extrasynaptic transmission was recently found to affect dopamine neurotransmitter delivery by anisotropic diffusion in the extracellular matrix,which is modulated by various extracellular matrix components such as fibronectin.The present study reviewed the neuroprotective effect of fibronectin in extrasynaptic transmission.Fibronectin can regulate neuroactive substance diffusion and receptor activation,and exert antineuroinflammatory,adhesive and neuroprotective roles.Fibronectin can bind to integrin and growth factor receptors to transactivate intracellular signaling events such as the phosphatidylinositol 3-kinase/protein kinase B pathway to regulate or amplify growth factor-like neuroprotective actions.Fibronectin is assembled into a fibrillar network around cells to facilitate cell migration,molecule and ion diffusion,and even drug delivery and treatment.In addition,the present study analyzed the neuroprotective mechanism of fibronectin in the pathogenesis of Parkinson’s disease,involving integrin and growth factor receptor interactions,and discussed the possible therapeutic and diagnostic significance of fibronectin in Parkinson’s disease.     

Clinical and molecular research of neuroacanthocytosis

Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated "acanthocytic" red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington’s disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.     

轻型缺血性卒中静脉溶栓后双重抗血小板疗效观察

目的 观察rt-PA静脉溶栓联合双重抗血小板治疗轻型缺血性卒中的有效性及安全性。 方法 以2013年12月-2016年12月在石家庄市第一医院连续住院治疗的轻型缺血性卒中患者为研究 对象,将其随机分为对照组、溶栓+单抗组和溶栓+双抗组。对照组不进行静脉溶栓,长期口服阿 司匹林（100 mg/d）抗血小板治疗;溶栓+单抗组在rt-PA静脉溶栓（0.9 mg/kg,最大剂量90 mg）基 础上长期单用阿司匹林（100 mg/d）抗血小板治疗;溶栓+双抗组在溶栓后单抗基础上加用氯吡格雷 （75 mg/d）双重抗血小板治疗,双抗治疗21 d后改为阿司匹林长期单抗治疗。随访3个月,有效性指标 为3个月时NIHSS 0～1分、Barthel指数（Barthel index,BI）95～100分和mRS 0～1分的比例,3个月时缺 血性卒中的复发率;安全性指标为治疗24 h出血转化和症状性出血转化的发生率。另外比较三组间 基线和3个月时血清hs-CRP和IL-6的水平差异。 结果 研究共纳入85例患者,对照组28例,溶栓+单抗组28例,溶栓+双抗组29例,全部患者均完 成3个月随访,无死亡患者。对照组、溶栓+单抗组和溶栓+双抗组3个月随访时NIHSS 0～1分比例分 别为46.43%、78.57%和93.10%,BI 95～100分比例分别为53.57%、82.14%和89.66%,mRS 0～1分 的比例分别为50.00%、82.14%和93.10%,三组上述有效性指标差异均有统计学意义,两两比较显 示,溶栓+双抗组高于溶栓+单抗组和对照组,溶栓+单抗组高于对照组,差异均有统计学意义;对 照组、溶栓+单抗组和溶栓+双抗组3个月时缺血性卒中复发率分别为32.14%、7.14%和3.45%,差异 有统计学意义。安全性指标方面,三组均无出血转化事件。对照组、溶栓+单抗组和溶栓+双抗组3 个月时的hs-CRP水平分别为11.92±3.58 mg/L、9.04±2.85 mg/L和6.04±2.65 mg/L,IL-6水平分别为 26.18±4.65 ng/L、16.11±6.93 ng/L和12.84±2.57 ng/L,三组上述炎症因子水平差异均有统计学意 义,其中溶栓+双抗组低于溶栓+单抗组和对照组,溶栓+单抗组低于对照组。 结论 对于急性轻型缺血性卒中患者,rt-PA静脉溶栓治疗后短期双重抗血小板治疗可显著改善患 者神经功能,降低炎症因子水平,降低复发率,且不增加出血风险。     

血浆甘油三酯水平与缺血性卒中出院结局关系研究

目的   探讨急性缺血性卒中患者入院时血浆甘油三酯（triglyceride,TG）水平与出院结局不良的关系。 方法  采用回顾性队列研究的方法,连续纳入内蒙古兴安盟人民医院2009年6月1日～2012年5月31日急性缺血性卒中患者,共计3351例。结局不良组定义为患者出院时改良Rankin量表（modified Rankin Scale,mRS）评分≥3分,对结局不良组和结局良好组患者间基线资料进行比较。用四分位数法将患者入院时血浆TG水平分为4组,用非条件Logistic回归分析入院时TG水平与急性缺血性卒中出院结局不良的关系,计算比值比（odds ratio,OR）及95%可信区间（confidence interval,CI）。 结果  研究对象中发生结局不良的共341例,发生率为10.2%。单因素非条件Logistic回归分析结果显示,TG相对最高分位数组（TG＞2.12?mmol/L）,第1、2、3分位数组（TG分别为≤1.06?mmol/L、1.06～1.46?mmol/L、1.46～2.12?mmol/L）的结局不良发生率差异有显著性（P＜0.001）。在调整了年龄、住院天数、发病到入院时间、缺血性卒中首发、吸烟、饮酒、心脏病史、心房颤动史、高血压、高血糖和心率后,相对于最高分位数组,第3分位数组的结局不良发生率差异无显著性（P=0.0758）,而第1、2分位数组结局不良发生率升高（均P＜0.0001）,其OR（95%CI）分别为11.883（1.307～2.714）和2.063（1.436～2.963）。 结论  急性缺血性卒中患者入院时低水平TG可能独立地增加出院结局不良的风险。