不同剂量马来酸桂哌齐特对脑梗死模型大鼠行为学影响

目的观察马来酸桂哌齐特对脑梗死模型大鼠行为学的影响;探索马来酸桂哌齐特大鼠实验的适合剂量。方法随机法把SD大鼠分为不同剂量马来酸桂哌齐特给药组和生理盐水组,分别给予不同剂量马来酸桂哌齐特及生理盐水干预5d后,以改良线栓法建立大脑中动脉阻塞脑梗死模型,并行行为学评定和头颅DWI检测;观察术后24h、72h和术后14d大鼠的行为学变化。结果模型大鼠术侧大脑皮层和基底节区均出现DWI高信号;术后24h各组大鼠偏瘫差异无统计学意义(p>0.05);术后72h和14d各组间偏瘫差异有统计学意义(P<0.05),表现为3.0 mg.kg-1组与6.0 mg.kg-1组评分值均降低,但此二组间评分降低差异无统计学意义(p>0.05)。结论马来酸桂哌齐特可能改善大脑中动脉阻塞脑梗死模型大鼠的偏瘫症状;3.0 mg.kg-1可能是经济有效的实验剂量。     

马来酸桂哌齐特预处理与大鼠脑缺血磁共振波谱变化

目的通过观察马来酸桂哌齐特预处理对急性脑缺血大鼠的头颅磁共振波谱(MRS)的影响,探讨该药物的脑保护作用。方法采用随机方法把SD大鼠分为马来酸桂哌齐特预处理组(给药组)和生理盐水预处理组(对照组)分别预处理5 d,然后以改良线栓法建立大脑中动脉阻塞脑缺血模型;观察术后8h、24h和72h实验大鼠MRS脑缺血侧和对侧相应区域NAA峰值比例(NAA*)和Cho峰值比例(Cho*),比较给药组和对照组在各观察时间点NAA*和Cho*的变化。结果给药组与对照组间,在术后8h、24h和72h实验大鼠MRS二侧NAA峰值比例(NAA*)均P<0.05,给药组NAA*均有升高;二侧Cho峰值比例(Cho*)比较,均P<0.05,给药组Cho*也均有升高(P<0.05)。结论马来酸桂哌齐特可能具有脑缺血保护作用。     

马来酸桂哌齐特对急性中重型颅脑损伤患者的疗效观察

目的 探讨马来酸桂哌齐特对急性中重型颅脑损伤患者的治疗作用。方法 将40例急性颅脑损伤患者随机分为马来酸桂哌齐治疗组(治疗组)和胞二磷胆碱治疗组(对照组),每组20例。所有患者药物治疗均在颅脑损伤后12小时内,在脱水、抗炎、神经营养等常规治疗基础上,治疗组加用马来酸桂哌齐特静脉滴注320mg/d,连续14天为1个疗程。对照组则加用胞二磷胆碱静脉滴注0.75g/d。根据意识觉醒时间、GCS评分、GOS评分以及TCD等,比较两组患者病情恢复情况。结果 急性中重型颅脑损伤治疗中,治疗组在意识觉醒时间上与对照组相比具有明显统计学意义(P<0.05);在不同时期GCS评分上,治疗组与对照组相比也具有明显统计学差异(P<0.05);GOS评分治疗组预后明显优于对照组,具有非常明显的统计学意义(P<0.01);TCD结果显示治疗组缓解脑血管痉挛效果优于对照组。结论 急性颅脑损伤早期应用马来酸桂哌齐特,可降低颅脑外伤后的病残程度,提高治疗效果。     

马来酸桂哌齐特对脑出血血肿体积和周围水肿带的影响

目的探讨马来酸桂哌齐特对高血压性脑出血血肿、水肿吸收及神经功能恢复的影响。方法90例高血压性脑出血患者,随机分为2组,对照组给予常规治疗,治疗组加用马来酸桂哌齐特(160mg/d)静滴。入组前、治疗7、21d测定神经功能评分、血肿和水肿体积。结果治疗7d,治疗组血肿体积、水肿体积及CSS评分明显小于对照组(P<0.05);治疗21d,治疗组无论血肿体积、水肿体积还是CSS评分均较对照组显著减少(P<0.05)。治疗21d神经功能评分与血肿体积相关性较高(P<0.01),与水肿体积无相关性(P>0.05)。结论马来酸桂哌齐特有利于高血压性脑出血水肿和血肿的吸收,改善脑出血的预后。     

马来酸桂哌齐特在颅脑损伤患者的治疗效果观察

目的通过随机分组对照观察探讨马来酸桂哌齐特对颅脑损伤患者的治疗效果。方法100例急性闭合性颅脑损伤患者，分为对照组和用药组，各50例病人。分析对比治疗后对照组和用药组的实验室各项检查指标：血液流变学，TCD检查结果等变化情况。并且对出院后3—6个月随访调查结果进行比较分析。结果治疗后血液流变学检查中，用药组（马来酸桂哌齐特组）各项指标均低于对照组（P〈0．05）。经颅多普勒检测结果显示：用药组的脑血流速度与对照组相比明显减慢（P〈0．05），血管痉挛得到缓解。对比两组出院后随访结果可以看出，用药组的GOS评分、KPS评分及Barthel指数预后明显好于对照组（P〈0.05）。结论初步证明急性颅脑损伤早期应用马来酸桂哌齐特可增加病变区的脑血流，改善微循环，改善颅脑损伤患者的预后。值得推广和进一步研究。     

脊髓磷酸化胞外信号调节蛋白激酶在大鼠切口痛痛觉过敏中的作用

目的 研究切口痛模型大鼠脊髓磷酸化胞外信号调节蛋白激酶(p-ERK)表达的变化及鞘内注射ERK上游激酶MEK的抑制剂U0126对其机械性痛觉阈值的影响.方法 雄性SD大鼠32只按随机数字表法分为假手术组、模型组、DMSO组、U0126组,每组8只,前2组大鼠鞘内注射生理盐水20μL;后2组大鼠分别鞘内注射DMSO、U0126 10μL后用生理盐水10μL冲管.注药10min后除假手术组外,后3组大鼠均制备右后足趾部切口痛模型.分别于制作模型前、模型后2、24、48 h应用YLS-3E电子压痛仪测定各组大鼠右足的机械性痛觉阈值.另取SD大鼠24只.分组方法 和处理同上,每组6只.每组分别在模型后2h、24h选择3只应用免疫组化染色检测大鼠脊髓背角p-ERK的表达.结果模型组、DMSO组大鼠模型后2、24、48 h及U0126组大鼠模型后2、24 h有足机械性痛觉阈值均低于模型前,差异有统计学意义(P<0.05);DMSO组和模型组之间比较大鼠机械性痛觉阈值差异无统计学意义(P>0.05);与同一时间点DMSO组和模型组比较,U0126组大鼠模型后2、24、48 h右足机械性痛觉阈值均增高,差异有统计学意义(P<0.05).免疫组化染色结果发现.与假手术组比较模型组和DMSO组模型后2、24 h患侧脊髓背角P-ERK免疫阳性细胞增多;与模型组和DMSO组同一时间比较,U0126组患侧脊髓背角p-ERK阳性细胞减少,差异均有统计学意义(P相似文献   

川芎嗪联合马来酸桂哌齐特治疗TIA疗效观察

目的观察川芎嗪联合马来酸桂哌齐特治疗短暂性脑缺血发作(TIA)的疗效。方法对55例TIA患者随机分为治疗组30例与对照组25例,2组均给予川芎嗪注射液160mg加5%葡萄糖或生理盐水250mL,静滴,1次/d;治疗组联合应用马来酸桂哌齐特320mg,加5%葡萄糖或生理盐水250mL静滴,1次/d,疗程均为14d。结果治疗组、对照组总有效率分别为93.3%和76.0%,2组比较差异有统计学意义(P<0.05)。结论川芎嗪联合马来酸桂哌齐特治疗TIA疗效显著,值得临床推广。     

脊髓磷酸化胞外信号调节蛋白激酶在大鼠切口痛痛觉过敏中的作用

Objective To investigate the changes of phosphorylated extracellular signal-regulated kinase (p-ERK) expression in the immunoreactive cells of the spinal dorsal hom after plantar incision,and explore the effects of intrathecal administration of MEK inhibitor U0126 on physiological pain threshold in rat models with incisional pain.Methods Thirty-two male SD rats were equally randomized into control group (C group),incisional pain group (I group),intrathecal U0126 group (Ugroup) and intrathecal DMSO group (D group).Twenty-μL physiological saline was injected into the rats of the C group and I group,respectively.Ten-μL DMSO and U0126 were injected into the rats in the U group and D group,respectively.Rat models with incisionai pain were induced in the other 3 groups except the C group.Mechanical hyperalgesia were evaluated by paw-pressure before and 2,24 h and 2 d after the inducement.Another 24 rats were treated as the above method and equally divided into 4 groups; the numbers of p-ERK immunoreactive cells in the dorsal horn were quantified to determine the ERK activation 2 and 24 after the model inducement.Results The paw-pressure threshold in I group and D group 2 and 24 h,and 2 d after the incision,and that in U group 2 and 24 h after the incision were significantly decreased as compared with that in C group (P<0.05); that between I group and D group showed no significant difference (P>0.05); that in the U group was obviously higher than that in the I group and D group at the same time points (P<0.05).Significantly increased numbers of p-ERK immunoreactive cells in the I group and D group were observed as compared with those in the C group (P<0.05); those in the U group was obviously decreased as compared with those in the I group and D group at the same time points (P<0.05).Conclusion Plantar incision-induced mechanical hyperalgesia can be prevented by intrathecal injection of U0126 through decreasing the expression of p-ERK positive cells,indicating that ERK pathway in the spinal dorsal horn involves in the incision-induced mechanical hyperalgesia in rats.     

脊髓磷酸化胞外信号调节蛋白激酶在大鼠切口痛痛觉过敏中的作用

Objective To investigate the changes of phosphorylated extracellular signal-regulated kinase (p-ERK) expression in the immunoreactive cells of the spinal dorsal hom after plantar incision,and explore the effects of intrathecal administration of MEK inhibitor U0126 on physiological pain threshold in rat models with incisional pain.Methods Thirty-two male SD rats were equally randomized into control group (C group),incisional pain group (I group),intrathecal U0126 group (Ugroup) and intrathecal DMSO group (D group).Twenty-μL physiological saline was injected into the rats of the C group and I group,respectively.Ten-μL DMSO and U0126 were injected into the rats in the U group and D group,respectively.Rat models with incisionai pain were induced in the other 3 groups except the C group.Mechanical hyperalgesia were evaluated by paw-pressure before and 2,24 h and 2 d after the inducement.Another 24 rats were treated as the above method and equally divided into 4 groups; the numbers of p-ERK immunoreactive cells in the dorsal horn were quantified to determine the ERK activation 2 and 24 after the model inducement.Results The paw-pressure threshold in I group and D group 2 and 24 h,and 2 d after the incision,and that in U group 2 and 24 h after the incision were significantly decreased as compared with that in C group (P<0.05); that between I group and D group showed no significant difference (P>0.05); that in the U group was obviously higher than that in the I group and D group at the same time points (P<0.05).Significantly increased numbers of p-ERK immunoreactive cells in the I group and D group were observed as compared with those in the C group (P<0.05); those in the U group was obviously decreased as compared with those in the I group and D group at the same time points (P<0.05).Conclusion Plantar incision-induced mechanical hyperalgesia can be prevented by intrathecal injection of U0126 through decreasing the expression of p-ERK positive cells,indicating that ERK pathway in the spinal dorsal horn involves in the incision-induced mechanical hyperalgesia in rats.     

马来酸桂哌齐特治疗急性脑梗死的疗效分析

目的 探讨马来酸桂哌齐特在辅助治疗急性脑梗死中的应用价值.方法 选择我院2011-03-2013-03收治的急性脑梗死患者80例,按不同治疗方式随机均分为对照组（常规治疗辅以血栓通）和实验组（常规治疗辅以马来酸桂哌齐特）,对2组患者的治疗效果进行比较.结果 实验组总有效率82.5%,明显高于对照组的55.0%（P＜0.05）;实验组治疗14 d后神经功能缺损评分均明显低于对照组（P＜0.05）;2组患者经治疗14 d后的血浆纤维蛋白原水平比较差异有统计学意义（P＜0.05）.结论 马来酸桂哌齐特治疗急性脑梗死效果显著,能明显改善患者神经功能,值得临床推广应用.     

大鼠脑缺血／再灌注后Fasl在脑内表达的变化和阿司匹林的干预作用

目的:观察阿司匹林(ASA)对大鼠局灶性脑缺血/再灌注(CI/RP)后脑内Fas配体(Fasl)表达的影响。方法:健康雄性Wistar大鼠60只,随机分成对照(A'-E')组和ASA(A-E)组,腹腔注射ASA80mg·kg-1作为干预因素,采用改良ZeaLonga线栓法制作局灶性脑缺血2h再灌注模型,用免疫组织化学染色法观察再灌注6、24、48h和4、7d脑组织Fasl表达。结果:脑缺血2h,再灌注6h在皮质及海马区即出现Fasl表达阳性细胞,24￣48h时达高峰。ASA组Fasl的表达与对照组相比P<0.05。结论:ASA可以抑制Fasl的表达,提示ASA通过抑制外源性凋亡信号的膜传导途径抑制细胞凋亡。     

细胞外信号调节激酶在实验性脑缺血损伤皮层区的动态时空变化

目的探讨细胞外信号调节激酶(ERK)在局灶性脑缺血/再灌注损伤梗死灶周皮层区的动态时空变化及其作用机制。方法建立兔大脑中动脉阻断(MCAO)局灶性脑缺血再灌注模型,应用免疫组化检测ERK1在脑缺血2h再灌注不同时间灶周皮层的动态表达规律,同时应用免疫组化和流式细胞术检测细胞凋亡状态的动态变化。结果免疫组化分析显示,缺血2h再灌注灶周皮层区1hERK1表达开始增多,6h数目明显增多,3d达高峰,然后逐渐下降,14d回落到基线水平,其阳性细胞数分别为0.22±0.02、0.25±0.02、0.42±0.04、0.14±0.02。其表达时程变化与灶周皮层凋亡的变化相一致。结论脑缺血损伤诱导ERK表达增强,ERK在介导神经细胞凋亡和缺血性损伤中起重要作用。这为脑缺血治疗提供了新的思路。     

大鼠局灶性脑缺血再灌注后磷酸化细胞外信号调节激酶表达的变化

目的研究细胞外信号调节激酶(extracellular signal-regulated kinase,ERK)在局灶性脑缺血再灌注中的作用。方法制备大鼠局灶性脑缺血再灌注模型,据Longa's的5级标准评分法进行神经功能评分,用免疫组织化学方法检测磷酸化ERK的表达,TUNEL染色检测神经元凋亡。结果在假手术组未检测到磷酸化的ERK表达,再灌注1h开始检测到阳性表达,再灌注4h达到峰值,12h下降;假手术组高倍镜视野仅见个别凋亡细胞,阴性对照片未检出阳性细胞,再灌注1h阳性细胞增加不明显,4h开始有明显的阳性细胞增加,24h细胞凋亡达到高峰,48h下降;磷酸化ERK阳性细胞计数与凋亡细胞数的相关分析显示相关系数(r)为-0.036,P=0.863,无统计学意义。结论局灶性脑缺血再灌注后磷酸化ERK表达增加,但其表达可能与神经元凋亡无关。     

西酞普兰对慢性应激大鼠行为及脑内ERK1/2磷酸化水平的影响

目的：探讨西酞普兰能否预防或减弱慢性应激的不良反应及其可能的作用机制。方法：对SpragueDawley大鼠,随机分为正常对照（NC）组,束缚应激（RS）组和西酞普兰预处理（CP）组。RS组大鼠每日束缚6h,连续21d。利用Morris水迷宫观察大鼠的空间记忆能力,运用免疫组织化学方法观察脑内细胞外信号调节激酶（extracellular signal-regulated kinase1／2,ERK1／2）磷酸化（p-ERK1／2）水平的改变。结果：RS组大鼠的Morris水迷宫试验目标象限活动时间和穿越站台次数比NC组大鼠显著减少（P〈0．05）;CP组大鼠的上述指标较RS组大鼠明显改善（P〈0．05）。RS组大鼠的前额皮质、杏仁内侧核以及杏仁皮质后内侧核中p-ERK1／2阳性细胞数均较NC组显著减少（P〈0．05）;而CP组大鼠以上各脑区中p-ERK1／2阳性细胞数均较RS组明显增多（P〈0．05）。结论：慢性束缚应激后大鼠的空间记忆明显受损;应激前和应激期间给予西酞普兰处理,能明显缓解应激对大鼠造成的记忆损伤,增加脑内ERK信号传导通路的活化。     

阿司匹林促进大鼠缺血脑组织脑源性神经营养因子的表达

目的:探讨不同剂量阿司匹林(Asp)对脑缺血/再灌注(CI/RP)损伤大鼠的神经保护作用及其对脑源性神经营养因子(BDNF)表达的影响。方法:采用线栓法建立大鼠大脑中动脉CI/RP模型,对CI/RP后大鼠进行肢体神经功能缺损评分:1~3分的48只大鼠入选。入选大鼠分为对照组、Asp小剂量组(20 mg.kg-1)、Asp中剂量组(80 mg.kg-1)和Asp大剂量组(320 mg.kg-1),于CI/RP术后每日腹腔注射Asp或溶媒,并进行神经功能缺损评分,72 h后处死,测定脑梗死体积和BDNF免疫组化检测。结果:CI/RP后24、48和72 h各Asp组大鼠与对照组相比,神经缺损评分明显降低(P<0.05或P<0.01),梗死灶体积显著减小(P<0.01),缺血区域BDNF表达显著增加(P<0.05或P<0.01)。对BDNF表达的作用Asp大剂量组的作用并不优于Asp小剂量组和中剂量组。结论:Asp可以减少CI/RP大鼠的脑梗死体积;促进内源性BDNF的表达可能是其神经保护的机制之一,Asp对BDNF表达的作用并非随Asp剂量的加大而增强。     

Regulation of extracellular signal-regulated kinase 1/2 influences hippocampal neuronal survival in a rat model of diabetic cerebral ischemia

Activation of extracellular signal-regulated kinase 1/2 has been demonstrated in acute brain ischemia. We hypothesized that activated extracellular signal-regulated kinase 1/2 can protect hippocampal neurons from injury in a diabetic model after cerebral ischemia/reperfusion. In this study, transient whole-brain ischemia was induced by four-vessel occlusion in normal and diabetic rats, and extracellular signal-regulated kinase 1/2 inhibitor （U0126） was administered into diabetic rats 30 minutes before ischemia as a pretreatment. Results showed that the number of surviving neurons in the hippocampal CA1 region was reduced, extracellular signal-regulated kinase 1/2 phosphorylation and KuT0 activity were decreased, and pro-apoptotic Bax expression was upregulated after intervention using U0126. These findings demonstrate that inhibition of extracellular signal-regulated kinase 1/2 activity aggravated neuronal loss in the hippocampus in a diabetic rat after cerebral ischemia/reperfusion, further decreased DNA repairing ability and ac- celerated apoptosis in hippocampal neurons. Extracellular signal-regulated kinase 1/2 activation plays a neuroprotective role in hippocampal neurons in a diabetic rat after cerebral ischemia/ reperfusion.     

Changes in Gene Expression in the Rat Hippocampus after Focal Cerebral Ischemia

Objective

The rat middle cerebral artery thread-occlusion model has been widely used to investigate the pathophysiological mechanisms of stroke and to develop therapeutic treatment. This study was conducted to analyze energy metabolism, apoptotic signal pathways, and genetic changes in the hippocampus of the ischemic rat brain.

Methods

Focal transient cerebral ischemia was induced by obstructing the middle cerebral artery for two hours. After 24 hours, the induction of ischemia was confirmed by the measurement of infarct size using 2,3,5-triphenyltetrazolium chloride staining. A cDNA microarray assay was performed after isolating the hippocampus, and was used to examine changes in genetic expression patterns.

Results

According to the cDNA microarray analysis, a total of 1,882 and 2,237 genes showed more than a 2-fold increase and more than a 2-fold decrease, respectively. When the genes were classified according to signal pathways, genes related with oxidative phosphorylation were found most frequently. There are several apoptotic genes that are known to be expressed during ischemic brain damage, including Akt2 and Tnfrsf1a. In this study, the expression of these genes was observed to increase by more than 2-fold. As energy metabolism related genes grew, ischemic brain damage was affected, and the expression of important genes related to apoptosis was increased/decreased.

Conclusion

Our analysis revealed a significant change in the expression of energy metabolism related genes (Atp6v0d1, Atp5g2, etc.) in the hippocampus of the ischemic rat brain. Based on this data, we feel these genes have the potential to be target genes used for the development of therapeutic agents for ischemic stroke.     

bFGF对大鼠局灶性脑缺血后神经细胞凋亡及Bcl-2、Bax的影响

目的探讨bFGF对缺血后神经细胞的保护作用。方法用线栓法制作局灶性脑缺血大鼠模型,于术前1h、术后第1天、第2天连续3天侧脑室注射bFGF,分1μg／d、2μg／d、4μg／d3组,观察缺血程度、梗塞体积、Bcl-2、Bax蛋白的合成。结果;bFGF能减轻脑缺血程度,减少梗塞体积(25．2％)及凋亡细胞数,提高半暗带内Bcl-2蛋白的合成,减低缺血灶内Bax蛋白的合成,各剂量组间无显著差异。结论bFGF可作为一种有效的神经细胞保护剂,保护神经细胞免受缺血的损害。     

Electroacupuncture alleviates cerebral ischemia and reperfusion injury via modulation of the ERK1/2 signaling pathway

Electroacupuncture(EA) has anti-oxidative and anti-inflammatory actions,but whether the neuroprotective effect of EA against cerebral ischemia-reperfusion(I/R) injury involves modulation of the extracellular regulated kinase 1/2(ERK1/2) signaling pathway is unclear.Middle cerebral artery occlusion(MCAO) was performed in Sprague-Dawley rats for 2 hours followed by reperfusion for 24 hours.A 30-minute period of EA stimulation was applied to both Baihui(DU20) and Dazhui(DU14) acupoints in each rat(10 mm EA penetration depth,continuous wave with a frequency of 3 Hz,and a current intensity of 1–3 m A) when reperfusion was initiated.EA significantly reduced infarct volume,alleviated neuronal injury,and improved neurological function in rats with MCAO.Furthermore,high m RNA expression of Bax and low m RNA expression of Bcl-2 induced by MCAO was prevented by EA.EA substantially restored total glutathione reductase(GR),glutathione(GSH) and glutathione peroxidase(GSH-Px) levels.Additionally,Nrf2 and glutamylcysteine synthetase(GCS) expression levels were markedly increased by EA.Interestingly,the neuroprotective effects of EA were attenuated when ERK1/2 activity was blocked by PD98059(a specific MEK inhibitor).Collectively,our findings indicate that activation of the ERK1/2 signaling pathway contributes to the neuroprotective effects of EA.Our study provides a better understanding of the regulatory mechanisms underlying the therapeutic effectiveness of EA.     

轻度低温对大鼠脑缺血时血中胞浆酶的影响

目的　研究轻度低温对大鼠脑缺血时血清胞浆酶含量变化的影响。方法　采用全自动生化分析仪检测血清肌酸激酶（ＣＫ）、肌酸激酶脑型同工酶（ＣＫ－ＢＢ）、乳酸脱氢酶（ＬＤＨ）以及天门冬氨酸氨基转换酶（ＡＳＴ）的含量。结果　常温（３６～３７℃）脑缺血２０ ｍ ｉｎ,血中ＣＫ、ＣＫ－ＢＢ和ＬＤＨ 的含量明显高于假手术组（Ｐ＜ ０．０５ 或Ｐ＜０．０１）;脑缺血６０ ｍ ｉｎ 和１２０ ｍ ｉｎ,血中ＣＫ、ＣＫ－ＢＢ、ＬＤＨ和ＡＳＴ的含量均明显高于假手术组（Ｐ＜ ０．０１）。低温组（３１～３２℃）大鼠脑缺血时血中ＣＫ、ＣＫ－ＢＢ、ＬＤＨ 和ＡＳＴ 的含量明显低于常温组（Ｐ＜ ０．０１）。结论　低温具有抑制脑缺血时血中胞浆酶的活性,延缓胞浆酶含量的增高以及细胞膜稳定作用