锂-毛果芸香碱致痫大鼠早期大脑NG2和O4表达及意义

目的探讨氯化锂-毛果芸香碱(匹罗卡品)致疒0 间大鼠早期大脑少突胶质前体细胞变化及意义.方法对雄性成年SD大鼠先后腹腔注射氯化锂、毛果芸香碱,制成癫癎持续状态动物模型;用免疫荧光组织化学法检测癎性发作后早期大鼠大脑皮质和海马CA1区NG2和O4阳性细胞数量.结果和对照组相比,除癫癎后1 d组外其余各组大鼠脑皮质内NG2和O4阳性细胞都有明显的增加;癫癎后1 d组海马CA1区的阳性细胞数明显减少;癫癎后7 d组皮质和海马CA1区NG2和O4阳性细胞数最多.结论氯化锂-毛果芸香碱致癎大鼠早期大脑NG2和O4表达增加,少突胶质前体细胞增多,并且和观测时间相关.     

新型促红细胞生成素衍生肽对毛果云香碱致急性癫小鼠的神经保护作用及机制探究

目的探究新型促红细胞生成素衍生肽(DEPO)对毛果云香碱致急性癫小鼠的保护作用,借助N-甲基-D-天冬氨酸(NMDA)损伤神经元模型初步探讨DEPO的作用机制。方法 (1)健康成年C57BL/6小鼠随机分为DEPO组(DEPO 500μg·kg~(-1))、EPO组(EPO 50μg·kg~(-1))、溶剂组(ACN+Milliq,0.2 mL/只)、生理盐水组(生理盐水,0.2 mL/只)。腹腔注射毛果云香碱建立急性癫小鼠模型,比较各组干预后癫发作潜伏期、发作严重程度、死亡率的差异。(2)采用NMDA兴奋性毒性损伤神经元模型,分为DEPO组(DEPO 100μg·mL~(-1)干预)、EPO组(EPO 5μg·mL~(-1)干预)、对照组和正常组,检测各组乳酸脱氢酶(LDH)释放率、细胞存活率(MTT法)。(3)拮抗EPOR实验,设置EPO+anti-EPOR组,DEPO+anti-EPOR组,提前4 h加入anti-EPOR(1∶100,biorbyt)中和EPOR,检测LDH释放率和细胞存活率。结果 DEPO组和EPO组癫发作潜伏期分别较溶剂组、生理盐水组显著延长(P0.05、P0.001)。各组间死亡率、癫发作严重程度比较,差异无统计学意义。DEPO组和EPO组LDH释放率较对照组显著降低(P0.01),细胞存活率较对照组显著增高(P0.001)。DEPO+anti-EPOR组、EPO+anti-EPOR组的LDH释放率分别较DEPO组和EPO组显著增高(P0.01),细胞存活率分别较DEPO组和EPO组显著降低(P0.001)。结论新型DEPO可以显著延长毛果云香碱致急性癫小鼠的癫发作潜伏期,并通过EPOR介导其减轻NMDA诱导的神经元兴奋性毒性损伤,发挥神经保护作用。DEPO在癫治疗中存在可能的应用前景。     

苯巴比妥对癫(癎)患者血浆型PAF-AH酶活力的影响

目的检测苯巴比妥癫癎患者血浆型血小板活化因子乙酰水解酶(PAF-AH)活性,了解苯巴比妥抗癫癎治疗对免疫功能的影响。方法采用ELISA法测定16例单药PB抗癫癎治疗未发作EP患者,14例单药PB抗癫癎治疗发作患者及16例健康对照组的血浆型PAF-AH活性。结果癫癎未发作组、癫癎发作组和健康对照组血浆型PAF-AH活性分别为(15.91±1.59)、(17.66±1.46)(、15.52±1.18)nmol/(min.μl),发作组血浆型PAF-AH活性高于健康对照组(P<0.01),未发作组与对照组无显著差异(P>0.05)。结论单药苯巴比妥抗癫癎治疗EP患者发作后血浆型PAF-AH活性升高,可能是机体的一种自我保护措施。     

小鼠急性致癎后海马活化素βA基因表达的变化与意义初探

目的探讨小鼠癫癎持续状态(Status epilepticus,SE)后海马活化素βA基因的表达与意义.方法采用毛果芸香碱诱导的SE小鼠模型,应用逆转录-聚合酶链反应(RT-PCR)及原位杂交观察SE后海马活化素βA基因表达的动态变化;应用尼氏染色观察海马病理形态结构的变化.结果SE后3 h海马活化素βA mRNA表达即显著增高,6 h达高峰,持续至约24 h后开始回落,48 h恢复近正常水平;活化素βA mR-NA表达最先在海马CA2及DG区上调,高峰时CA3区亦见明显表达,48 h后仅CA2区仍可见阳性表达;海马活化素βA mRNA水平与神经元抗损伤力有关.结论毛果芸香碱诱导的SE能明显上调海马活化素βAmRNA表达,其水平的上调可能有助于增强海马神经元抗兴奋性损伤的能力.     

难治性癫癎患者外周血中MDR1基因的表达及临床意义

目的 研究难治性癫癎患者外周血中多药耐药1(MDR1)基因的表达以及抗癫癎药物和癎性发作在难治性癫癎多药耐药发生中的作用.方法 采用逆转录聚合酶链反应(RT-PCR)半定量检测120例研究对象外周血中MDR1基因mRNA的表达.根据析因设计分癎性发作和抗癫癎药物两个因素,共分为A组(难治性癫癎组)、B组(癫癎治疗有效组)、C组(癎性发作未用药组)和D组(健康正常对照组),各30例.结果 4组的外周血中MDR1基因的表达水平明显不同(F=4.456,P=0.005),其中癎性发作引起MDR1mRNA的表达明显增高(F=10.005,P=0.002),抗癫癎药物的作用则不明显(F=0.919,P=0.340),抗癫癎药物与癎性发作两者之间没有交互作用(F=2.445,P=0.121).结论 难治性癫癎患者外周血中MDR1基因mRNA的表达上调是癎性发作而非使用抗癫癎药物的结果,外周血中MDR1基因mRNA表达水平的监测可以作为评价癫癎耐药的一项指标.     

雌激素调控瞬时外向钾通道对大鼠慢性颞叶癫发作的影响

目的探讨雌激素对大鼠慢性颞叶癫发作的影响及其与瞬时外向钾通道(kv4.2)之间的关系。方法 SD雌性大鼠随机分为正常对照组、去势对照组、正常致组、去势致组。应用毛果芸香碱诱导大鼠癫持续状态(SE),观察大鼠行为学变化。经4周后成为慢性颞叶癫大鼠。Western bolt方法检测大鼠海马瞬时外向钾通道Kv4.2蛋白表达水平。结果与正常致组比较,去势致组达到SE的潜伏期延长、死亡率降低,但差异无统计学意义(P0.05);去势致组的癫发作强度较正常致组轻,差异有统计学意义(P0.05)。去势致组和正常致组在SE 4周后海马Kv4.2均较正常对照组显著升高,均差异有统计学意义(P0.05和P0.01)。去势对照组和去势致组比较,均未见对Kv4.2蛋白表达产生影响,说明Kv4.2蛋白表达升高为癫发作所致。结论大鼠癫发作后Kv4.2表达增加、瞬时外向钾电流增强、神经冲动的发放频率减慢,可能是产生代偿性自我保护反应的结果;虽然去势雌性大鼠未对Kv4.2表达产生影响,但出现潜伏期延长和死亡率降低、发作强度降低的行为学趋势,提示低剂量雌激素可能存在对癫发作的保护作用。     

胞二磷胆碱、氯脂醒、神经节苷脂对大鼠癫(癎)的影响

目的 探讨胞二磷胆碱、氯脂醒、神经节苷脂(GM1)对青霉素致(癎)大鼠行为学及脑皮层电图的影响,为临床治疗颅脑损伤和外伤后癫(癎)提供理论依据.方法 制作大鼠癫(癎)模型,观察并比较对照组、模型组、胞二磷胆碱组、氯脂醒组、GM1组大鼠的行为学及脑皮层电图表现.结果 胞二磷胆碱、氯脂醒、GM1均不能阻止青霉素诱导的大鼠癫(癎)发作.胞二磷胆碱、GM1可以延长青霉素诱导的大鼠癫(癎)(癎)波潜伏期、阵挛强直波潜伏期,减少阵挛强直总时间.结论 胞二磷胆碱、氯脂醒、GM1均不能阻止青霉素诱导的大鼠癫(癎)发作;胞二磷胆碱、GM1可以延长青霉素诱导的大鼠癫(癎)(癎)波潜伏期、阵挛强直波潜伏期,减少青霉素腹腔注射后50 min内的阵挛强直总时间.     

17例弈棋相关性癫(癎)发作临床特点分析

目的:分析与弈棋相关的癫(癎)发作患者的临床特征.方法:选取2012年1月～2015年12月上海交通大学医学院附属新华医院神经内科癫(癎)数据库中与弈棋相关的癫(癎)发作患者17例进行随访,收集患者的人口学资料、起病年龄、癫(癎)发作类型、发作频率、影像学资料以及脑电图资料等,并对患者数据进行统计学分析.结果:17例患者均表现为与弈棋相关的癫(癎)发作,其中12例为棋奕性癫(癎),2例单次发作,3例为继发性癫(癎)弈棋相关性发作.2例棋奕性癫(癎)患者的动态脑电图提示(痫)样放电,2例继发性癫(癎)弈棋相关性发作患者的动态脑电图亦发现异常放电.行为学干预有助于预防再次发作,而抗癫(癎)药物(AED)并无特异疗效.结论:出现弈棋相关性癫(癎)发作的患者首先需明确病因.继发性癫(癎)弈棋相关性发作可考虑AED治疗;反射性癫(癎)行为学干预有助于预防再次发作,AED治疗非首选.     

依达拉奉对癫(癎)大鼠海马肿瘤坏死因子-α和白介素-1β表达的影响

目的 探讨依达拉奉对癫(癎)大鼠海马肿瘤坏死因子(TNF)-α和白介素(IL)-1β表达的影响.方法 36只Wistar大鼠随机分为依达拉奉组、癫(癎)组和正常对照组.应用戊四氮腹腔注射制作癫(癎)模型.依达拉奉组在造模前0.5 h及造模后立即、造模后12 h分别予以腹腔注射依达拉奉3 mg/kg.癫(癎)大鼠于造模后进行行为学观察.应用酶联免疫吸附(ELISA)法检测各组大鼠海马TNF-α和IL-1β的表达.结果 造模后,癫(癎)组12只大鼠均为Ⅴ级发作;依达拉奉组3只大鼠为Ⅴ级发作,2只为Ⅳ级发作,5只为Ⅲ级发作,2只为Ⅱ级发作.与正常对照组比较,依达拉奉组与癫(癎)组大鼠海马TNF-α、IL-1β的表达水平均明显增高(P<0.05～0.01);与癫(癎)组比较,依达拉奉组大鼠海马TNF-α、IL-1β的表达水平均明显降低(均P<0.01).结论 依达拉奉能明显降低癫(癎)大鼠海马TNF-α和IL-1β的表达水平,从而发挥抗癫(癎)作用.     

全面强直-阵挛性发作癫(癎)168例随访观察

的探讨全面强直-阵挛性发作(GTCS)癫(癎)患者的预后.方法对168例GTCS患者进行11～22年的临床随访,观察抗癫(癎)药物疗效及治疗后的智能和生活质量.结果随访结束时,停药21例(12.5%),仍服药者147例(87.5%);165例(98.2%)正规抗癫(癎)治疗能有效控制癫(癎)发作,117例(84.8%)停药1.33年后复发,继续服药仍能控制,无1例发生癫(癎)持续状态.28例(16.67%)患者出现精神症状,以情感障碍较突出.癫(癎)组总智商与正常对照组比较无差异,发作控制组与未控制组比较无差异(均P>0.05),但生活质量癫(癎)组明显低于正常对照组(P<0.01).结论 GTCS患者须长期服药治疗,智力不受影响,但生活质量低于正常人.服药治疗的同时配合心理治疗,可提高其生活质量.     

Alterative application of five anticonvulsants according to the half life for the treatment of status epilepticus in children with severe viral encephalitis

BACKGROUND: Traditional subhibernation therapy may easily cause complications, such as respiratory depression and hyportension because of application of chlorpromazine hydrochloride and promethazine in a large dosage. OBJECTIVE: To observe therapeutic effect of modified subhibernation therapy (alterative application of five anticonvulsants according to the half life) on status epilepticus in children with severe viral encephalitis (VE). DESIGN: Contrast observation. SETTING: Department of Pediatrics, the First Hospital of Jilin University. PARTICIPANTS: The participants in present study were 96 patients with severe viral encephalitis including 52 boys and 44 girls who received treatment in the Department of Pediatrics, the First Hospital of Jilin University from February 2000 to March 2006. All children met the diagnostic criteria of Zhufutong Practice Pediatrics (the seventh edition). Two weeks ago, they ever got upper respiratory infection or enteronitis and so on before the onset, spirit abnormal, behavior disorder, limbs act disorder, vomit, headache, convulsion, nervous system masculine signs such as limbs act disord, autonomic nerve damage manifestation, brain nerve palsy, dysreflexia, meningeal irritation sign, cerebrospinal fluid and electroencephalography (EEG) abnormity. All parents provided the confirmed consent. The patients were randomly divided into control group (n =40) and experimental group (n =56). METHODS: Patients in the control group received anticonvulsion, ice compress and routine treatment. The convulsion was treated with five drugs: 0.5 mg/kg wintermin and phenergan, respectively, 100 g/L chlorpromazine hydrochloride (0.5 mL/kg), 5 mg/kg luminal, 0.3 mg/kg ansiolin. When convulsion attacked, those five drugs were given alternatively; however, those were not given if the convulsion did not attack. Children in the experimental group were treated with improved subhibernation therapy based on routine treatment. The dosages of anticonvulsants were as the same as those in the control group. Based on the half life, every drug was alternated every 4–6 hours. In addition, anticonvulsants administrated for 2 successive days whether tic attacked or not. Then the hypnotic was removed gradually. MAIN OUTCOME MEASURES: Therapeutic efficacy, time of disappeared clinical symptoms and physical sign, and security of administration. RESULTS: All the 96 patients were involved in the final analysis. ① Total effective rate and reliability: Total effective rate was higher in the treatment groups than the control group (χ2=5.871 7, P < 0.05). All patients did not have respiratory depression and side effects. ② Time of disappeared clinical symptoms and physical sign: Recovery time of convulsion, fever, headache and vomit was shorter in the treatment group than that in the control group, and there was significant difference (t =17.612 1–34.330 7, P < 0.05); in addition, symptoms of status epilepticus were relieved obviously. Meanwhile, recovery time of paralysis, coma and anepia was shorter in the treatment group than that in the control group, and there was significant difference (t =10.660 8–24.700 8, P < 0.05). CONCLUSION: Therapeutic effect of improved subhibernation therapy on status epilepticus induced by severe viral encephalitis is positively and safer.     

致死剂量N-甲基-D-天冬氨酸中毒模型小鼠对丙泊酚的反应*☆

背景：丙泊酚具有较好的抗惊厥作用,但其作用机制尚不清楚。 目的:观察丙泊酚对致死剂量N-甲基-D-天冬氨酸中毒模型小鼠的行为学及存活率的影响。 方法：建立N-甲基-D-天冬氨酸致死模型昆明小鼠,给药前10 min,腹腔注射丙泊酚12.5,25,50,75,100 mg/kg,观察中毒小鼠的行为学改变及存活率,阳性对照组在造模前腹腔注射非特异性的N-甲基-D-天冬氨酸受体拮抗剂地佐环平 2 mg/kg,为排除丙泊酚溶剂脂肪乳可能的作用,设定了脂肪乳组,在造模前腹腔注射等容积的脂肪乳作为对照。 结果与结论：腹腔注射N-甲基-D-天冬氨酸175 mg/kg可导致小鼠全身惊厥发生并且很快死亡,而提前给予丙泊酚12.5,25,50,75,100 mg/kg后,可见其可剂量依赖性的对抗小鼠惊厥的发生,并降低小鼠的死亡率,地佐环平(2 mg/kg)可完全预防惊厥发生,而脂肪乳不能抑制惊厥的发生,对致死剂量N-甲基-D-天冬氨酸中毒模型小鼠无保护作用。提示丙泊酚的抗惊厥作用可能与N-甲基-D-天冬氨酸受体有关。     

硫酸镁对大鼠脑弥漫性轴索损伤海马区Bcl-2和Bax蛋白表达影响的研究

目的研究脑弥漫性轴索损伤后神经细胞迟发性死亡的机制,探讨镁离子对大鼠脑弥漫性轴索损伤后神经元的保护作用。方法采用Marmarou方法制备大鼠重度脑弥漫性轴索损伤模型,分为创伤组(n=25)、生理盐水组(n=40)和硫酸镁组(n=40)。硫酸镁组伤后半小时给予25%硫酸镁(750μmol/kg),生理盐水组在相同时间给予等量的生理盐水腹腔注射,于伤后6小时、24小时、3天、5天及7天5个时相点处死。采用HE染色、免疫组织化学技术动态观察大鼠海马区的组织病理改变,Bcl-2和Bax蛋白的表达情况,以及使用硫酸镁干预后对上述表达的影响。结果①Bcl-2蛋白的表达:假手术组大鼠海马区仅见极少量Bcl-2阳性细胞,着色淡。在伤后6小时即有大量的Bcl-2阳性细胞,随时间渐增,24小时达到高峰,3～7天逐渐减少。②Bax蛋白的表达:在DAI后大鼠海马区有大量Bax阳性细胞,在伤后6小时就有所增加,24小时显著增加,3天达到高峰。Bcl-2/Bax值在损伤后随时间逐渐上升。③硫酸镁组中,海马区的Bax表达与对照组相比有所减少,而Bcl-2相应增加,Bcl-2/Bax比值也是上调的,均有统计学意义(P<0.05)。结论大鼠脑弥漫性轴索损伤后,海马区神经元存在有迟发性细胞死亡即凋亡现象。Bax与Bcl-2参与细胞凋亡过程。硫酸镁可通过抑制Bax蛋白,上调Bcl-2蛋白,减少神经细胞凋亡,对促进神经细胞修复和功能重塑有益。     

咪达唑仑治疗小儿惊厥持续状态疗效观察

目的观察咪达唑仑治疗小儿惊厥持续状态的疗效及安全性。方法小儿惊厥持续状态患儿58例,随机分为治疗组与对照组各29例,治疗组予咪达唑仑持续静脉推注治疗,对照组予地西泮持续静脉滴注治疗。结果治疗组与对照组有效率分别为96.6%和72.4%,2组比较差异有统计学意义(χ2=4.73,P<0.05);治疗组未见明显不良反应。结论咪达唑仑用于治疗小儿惊厥持续状态是安全有效的。     

Influence of nitric oxide synthase inhibitor on gerbil behavior after hyperbaric oxygen-induced convulsion★

BACKGROUND:Studies have reported that nitric oxide synthase (NOS) inhibitor can prolong the latency of hyperbaric oxygen-induced convulsion (HBOC). However, there are very few reports addressing the influence of NOS inhibitor on mental behavior. OBJECTIVE: To investigate behavioral changes after HBOC in gerbils, as well as the influence of NOS inhibitor. DESIGN, TIME AND SETTING: Randomized experiments were performed in the Laboratory of Hyperbaric Pressure and Diving Physiology, Naval Medical Research Inst...     

立体定向脑室注射代谢性谷氨酸受体1拮抗剂对SAH损伤影响的实验

目的研究侧脑室注射代谢性谷氨酸受体1(mGluR1)拮抗剂LY367385是否能减轻小鼠蛛网膜下腔出血(subarachnoid hemorrhage,SAH)后脑组织损伤。方法采用非开颅血管内线栓法制备小鼠SAH模型,随机分为3组:对照组(control组)、模型组[(SAH+生理盐水(NS)组)]、mGluR1拮抗剂LY367385组(SAH+LY367385组),于SAH后10min侧脑室注射NS或LY367385(500nmol)5μl,术后行神经功能评分。分别在SAH后6、24、48h3个时相点取右侧脑组织标本,采用蛋白免疫印迹法(Western biotting)检测mGluR1、p-ERK1/2蛋白的表达;用原位末端标记法(TUNEL)检测神经细胞凋亡情况。结果与对照组比较,模型组小鼠神经功能评分显著降低,各组小鼠mGluR1和p-ERK1/2蛋白均有不同程度增强,凋亡细胞增多。与模型组比较,拮抗剂组小鼠神经功能评分增加,mGluR1、p-ERK1/2蛋白表达均有不同程度下调,神经细胞凋亡数目减少。结论 (1)SAH后mGluR1的表达增强可通过激活ERK信号途径诱导神经细胞凋亡;(2)mGluR1选择性拮抗剂LY367385对脑血管痉挛(cerebral vaso-spasm,CVS)损伤具有保护作用。     

ERK1/2 activation in reactive astrocytes of mice with pilocarpine-induced status epilepticus

Abstract

Objective: To investigate the activation pattern of extracellular signal-regulated kinase 1/2 (ERK1/2) in the hippocampus of mice during pilocarpine-induced status epilepticus (SE) and its relationship with reactive astrogliosis.

Methods: Status epilepticus (SE) models were established by intraperitoneal injection of pilocarpine. The intervention group received the ERK1/2 signaling pathway inhibitor SL327 before the pilocarpine injection. We evaluated the SE model group, the intervention group and the control saline-treated group, at 6 hours and 3 days after initiation of the seizure. Phosphorylated activated ERK1/2 and glial fibrillary acidic protein (GFAP) were labeled with both single-labeling and sequential single-labeling immunohistochemical techniques.

Results: Among the pilocarpine-treated (SE model) mice, strong immunohistochemical staining of phospho-ERK1/2 was observed in the neurons and astrocytes of the hippocampus at 6 hours after initiation of SE, whereas staining on the third day of SE was not different from the control saline-treated mice. In the SL327-treated mice (intervention group), SL327 effectively blocked the ERK1/2 activation and little gliosis could be detected at 6 hours and 3 days after initiation of SE; the levels of phospho-ERK1/2 remained low, but the level of gliosis was similar to that of SE mice.

Conclusion: The ERK1/2 signaling pathway plays an important role in the early stage of reactive astrogliosis in mice with pilocarpine-induced SE.     

Toll样受体4/核因子-κB信号通路在癫癎持续状态大鼠海马损伤中的作用

目的 通过观察癫疴持续状态(status epilepticus,SE)后大鼠海马Toll样受体4(Toll-like receptor 4,TLR4)及核因子-κB(nuclear factor KB,NF-κB)的表达;并观察应用NF-κB抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)后,对TLR4/NF-κB信号通路及海马损伤的影响,探讨TLR4/NF-κB信号通路在SE后大鼠海马损伤的发生发展过程中的作用.方法 106只SD大鼠随机分为对照组(A组)、SE组(B组)和PDTC干预组(C组),其中B组再随机分为B1～B4组(分别于惊厥后4、24、48和72 h处死),B组和C组采用氯化锂.匹罗卡品法制作大鼠SE模型,C组在大鼠惊厥终止后30 min,给予100 mg/kg PDTC腹腔注射,每天1次,连用3 d.光镜下观察大鼠海马病理学改变;免疫组织化学法检测海马TLR4和NF-κB/p65蛋白的表达变化;逆转录-聚合酶链反应(RT-PCR)技术检测海马TLR4 mRNA表达的动态改变.结果 长程惊厥发作后,脑内神经元损伤存在动态变化,在72 h内随着观察时间的延长,神经元损伤逐渐加重,C组改变较B4组明显减轻.B组各时间点TLR4蛋白的表达(B1组0.1287±0.0260,B2组0.1296±0.0285,B3组0.1330 4-0.0329,B4组0.1604 4-0.0457)均明显高于A组(0.0964±0.0324,t=0.0641～0.3236,P<0.05),并随时间延长明显增高;C组TLR4蛋白表达(0.1271±0.0330)较B4组显著降低(t=-0.0334,P<0.01).B组可见NF-κB/p65蛋白在胞核内有不同程度表达,与A组比较差异有统计学意义(P<0.05);C组与B4组比较,NF-κB/p65蛋白表达水平明显降低(P<0.01).B组各时间点TLR4 mRNA的表达均较A组(0.268±0.072)高(P<0.05),且随时间延长逐步升高,惊厥后72 h达到高峰(1.242±0.100);C组海马TLR4 mRNA的表达(0.984±0.263)明显低于B4组(t=-0.2578,P<0.05).各组TLR4的表达情况与NF-κB/p65一致.结论 ,TLR4及NF-κB/p65在SE后的大鼠海马中表达升高,NF-κB抑制剂PDTC可以下调TLR4的表达,并减轻惊厥后海马病理损伤程度,提示TLR4/NF-κB信号通路在惊厥后海马损伤的发生发展过程中起促进作用.     

川芎嗪对MPTP所致小鼠多巴胺能神经元损伤的保护作用及机制

目的 探讨川芎嗪对MPTP所致小鼠多巴胺能神经元损伤的保护作用及可能机制.方法 C57BL/6J雄性小鼠32只,随机分为4组:生理盐水对照组(NS+NS)、生理盐水组(NS+MPTP)、川芎嗪高剂量组(LT50+MPTP)、川芎嗪低剂量组(LT20+MPTP),每组8只动物.分别采用HPLC法检测纹状体中DA的含量,免疫组化检测黑质中TH阳性细胞数,荧光显色法检测黑质SOD活力、GSH含量.结果 LT50+MPTP组纹状体DA含量、黑质DA神经元数量、黑质SOD活力、黑质GSH含量较NS+MPTP组显著增高(P<0.01).结论 川芎嗪对对MPTP所致的小鼠多巴胺能神经元损伤具有保护作用,其保护机制可能与其调节调节小鼠黑质中的SOD、GSH含量有关.

Abstract：

Objective To investigate the neuroprotective effects and mechanisms of ligustrazine on the MPTP-in-duced dopaminergic neurodegeneration in a mouse model of PD. Methods Male C57BL/6J mice were randomly divided into following four treatment groups ( n = 8/group) : ( 1 ) the saline control group ( NS + NS), mice pretreated with saline followed by saline treatment;(2) the mice pre-treated with saline followed by saline treatment (NS + MPTP) ; (3) the mice pretreated with 50mg/kg of ligustrazine followed by MPTP treatment (LT50 + MPTP) ;(4) the mice pretreated with 20mg/kg of ligustrazine followed by MPTP ( LT20 + MPTP). HPLC,immunohistochemistry and fluorimetry were used. Results The residual DA contents, TH-IR positive cells, SOD activity and GSH content in the mice pretreated with 50mg/kg ligustrazine ( LT50 + MPTP) were significantly higher than those of the saline-pretreatd mice ( NS + MPTP) ( P < 0.01 ).Conclusions Ligustrazine ameliorated MPTP-induced dopaminergic neurodegeneration in mice. The neuroprotective effect of ligustrazine may be associated with their strong antioxidant capacity in vivo.     

抗癫痫药物对大鼠记忆和学习功能影响的研究

目的探讨抗癫痫药物对大鼠认知功能的影响。方法健康雄性性成熟SD大鼠70只,随机分为正常对照组(NS组)、癫痫对照组(PTZ组)、卡马西平(CBZ)组、苯妥英钠(PHT)组、丙戊酸钠(VPA)组、妥泰(TPM)组及拉莫三嗪(LTG)组,每组10只。除NS组外其他6组用PTZ点燃。抗癫痫治疗2周后用Morris水迷宫测试认知功能。采用方差分析进行统计学处理。结果PTZ组学习成绩提高快(P<0.05,P<0.01)。卡马西平组、丙戊酸钠组、拉莫三嗪组测试成绩捉高很快(P<0.01),优于NS组。苯妥英钠组测试成绩提高较慢(P<0.05),与NS组比较无明显差异。妥泰组测试成绩提高慢,各次、各天之间差异无显著性(P>0.05),较NS组差。在寻找平台象限和在平台象限逗留时间的测试中,妥泰寻找时间最长,逗留时间最短,两项成绩均低于其他组(P<0.05,P<0.01);其他各组之间差异无显著性。结论PHT可能损害大鼠的学习、判断功能,TPM还可损害大鼠的记忆功能。