柴胡疏肝汤对戊四氮致痫大鼠海马及额叶皮质c-fos表达的影响

目的 观察柴胡疏肝汤对戊四氮致痫大鼠海马及额叶皮质c-fos表达的影响.方法 选取经戊四氮诱导制作的癫痫模型大鼠48只,按随机数字表法分成6组:癫痫模型组、德巴金组、定痫丸组、柴胡疏肝汤低剂量组、柴胡疏肝汤中剂量组和柴胡疏肝汤高剂量组,每组各8只;另设正常对照组8只.正常对照组和癫痫模型组常规饲养,其他各组给予药物德巴金,定痫丸,低、中、高剂量柴胡疏肝汤处理,均连续灌胃治疗5周.免疫组化染色检测各组大鼠海马及额叶皮质c-fos的表达情况.结果 戊四氮致痫后大鼠海马及额叶皮质c-fos表达明显增强,而应用中、高剂量的柴胡疏肝汤,德巴金和定痫丸治疗后,大鼠海马及额叶皮质c-fos表达均明显减弱,与癫痫模型组比较差异均有统计学意义(P<0.05),而柴胡疏肝汤低剂量组大鼠海马及额叶皮质c-fos表达无明显减弱.结论 柴胡疏肝汤的抗癫痫作用机制可能与其含有柴胡皂甙及其他多种有效的抗癫痫成份多靶点干预海马及额叶皮质c-fos表达水平有关.

Abstract：

Objective To observe the effect of chaihushugantang on the expression of c-fos in the hippocampus and frontal lobe cortex of pentylenetetrazole (PTZ)-induced epileptic rats. Methods Forty-eight PTZ-induced epileptic rats were randomly divided into 6 groups: epileptic model group,Valproate treatment group, Dingxianwan treatment group, and lower-dose, medium-dose and high-dose chaihushugantang treatment groups (n=8). Normal control group was also employed (n=8). The epileptic rats in the normal control group and epileptic model group were fed normally. Rats of the treatment groups were performed intragastric administration of medicines (Valproate, Dingxianwan and chaihushugantang) for 5 weeks in succession respectively. The expression of c-fos in the hippocampus and frontal lobe cortex of all the rats was observed. Results The expression of c-fos in the hippocampus and frontal lobe cortex of rats in the epileptic model group was significantly increased, while the c-fos expression in the hippocampus and the frontal lobe cortex of rats in the medium-dose and high-dose chaihushugantang treatment groups and Valproate treatment group and Dingxianwan treatment group was significantly decreased as compared with that in epileptic model group (P<0.05). But the c-fos expression in the hippocampus and the frontal lobe cortex of rats in the low-dose chaihushugantang treatment group showed no obvious decrease. Conclusion Chaihushugantang has good antiepileptic effect, might through affecting the c-fos expression in the epileptic rats. The antiepileptic mechanism of chaihushugantang can be related to saikosaponins and other antiepileptic constituents in it.     

毛喉素在大鼠脑损伤后血脑屏障损害中的作用

目的 探讨提高细胞内cAMP制剂毛喉素在脑损伤后血脑屏障损害中的作用.方法 雄性SD大鼠60只按随机数字表分为正常对照组、假手术组、脑损伤组和毛喉素治疗组,每组15只.后2组大鼠采用改进的自由落体硬膜外撞击方法制作脑损伤模型,治疗组大鼠于伤后0.5 h腹腔注射毛喉素,伤后24 h处死大鼠(处死前1 h静脉注射20 g/L伊文氏蓝),应用荧光显微镜观察伊文氏蓝的渗出,分光光度计恻定脑组织伊文氏蓝的含量.结果 正常对照组和假手术组大鼠损伤组织周围伊文氏蓝无明显渗出,脑损伤组伊文氏蓝大量渗出,治疗组与脑损伤组比较,伊文氏蓝渗出明显减少;脑损伤组大鼠左侧皮质、海马和右侧皮质、海马伊文氏蓝含量明显高于正常对照组和假手术组,差异有统计学意义(P＜0.05);毛喉素治疗组左侧皮质伊文氏蓝含量明显低于脑损伤组,但仍高于正常对照组,差异有统计学意义(P＜0.05).结论 提高细胞内cAMP制剂毛喉素能明显阻止血脑屏障开放.

Abstract：

Objective To explore the role of forskolin, a reagent elevating the cellular content of cAMP, in blood-brain barrier (BBB) damage in rats after cerebral injury damage. Methods Sixty male SD rats were equally randomized into normal control group, sham-operated group, injured group and forskolin treatment group. Rat models of cerebral injury in the later 2 groups were induced by the improved device of Feeney weight-dropping. Foskolin treatment group was peritoneally administered forskolin 5 mg/kg 0.5 h after the brain injury. Twenty g/L Evens blue was given through intravenous injection 23 h after the injury; all the rats were sacrificed 24 h after the injury. The permeation of Evens blue was observed qualitatively with a fluorescence microscope and measured quantitatively with a spectrophotometer. Results No obvious permeation of Evens blue was noted in the surrounding areas of the damaged tissue of normal controls and sham-operated group; Evans blue significantly permeated in the injured group; as compared with that in the injured group, the permeation of Evens blue was significantly decreased in the forskolin treatment group (P＜0.05). The level of Evens blue in the cortex and hippocampus of both side of the brain in the injured group was significantly higher that that in the normal controls and sham-operated group (P＜0.05); the level of Evens blue in the cortex of the left side of the brain in the forskolin treatment group was significantly lower that that in the injured group, but obviously higher than that in the normal controls and sham-operated group (P＜0.05).Conclusion Forskolin, the reagent elevating the cellular content of cAMP, can significantly prevent BBB opening.     

人工寒潮对颈动脉粥样硬化性大鼠血压的影响

目的 探讨人工寒潮对颈动脉粥样硬化性大鼠血压的影响以及尼莫地平的干预作用.方法 将SD大鼠按随机数字表法分为正常组、假手术组和颈动脉粥样硬化组,其中颈动脉粥样硬化组再分为非寒潮组、寒潮组和干预组3个亚组,除非寒潮组外其他各组均经历人工寒潮3d,寒潮组并给予等剂量生理盐水灌胃3 d,干预组并给予尼莫地平干预,分别测量各组经历寒潮前后的血压.结果 (1)寒潮前假手术组及颈动脉粥样硬化组血压明显高于正常组,比较差异有统计学意义(P＜0.05).(2)寒潮后正常组、假手术组及寒潮组的血压较寒潮前明显增高,干预组血压较寒潮前明显下降,比较差异均有统计学意义(P＜0.05).(3)正常组、假手术组及寒潮组之间寒潮前后血压的差值比较无统计学差异.(4)与寒潮组相比,干预组的血压差值明显降低,比较差异有统计学意义(P＜0.05).结论 人工寒潮可以使正常大鼠及颈动脉粥样硬化性大鼠血压升高,尼莫地平可以预防寒潮导致的血压升高.

Abstract：

Objective To study the effect of artificial cold exposure (ACE) on the level of blood pressure in carotid atherosclerotic rats, and the prophylactic effect of nimodipine on it. Methods One hundred and thirty SD rats were randomly divided into normal group (n=10), sham-operated group (n=10), and carotid atherosclerotic (CAS) group (n=110). High-fat diet was given to the sham-operated group and CAS group; normal diet was given to the control group. Then, 105 alive rats in the CAS group were further sub-divided into non-ACE group (n=40), ACE group (n=38) and nimodipine treatment group (n=37). All the groups were subjected to ACE for 3 d except non-ACE group, and kept at 22 °C throughout the experiment. During the ACE, an intragastric administration of nimodipine was given to the nimodipine treatment group. The changes of the blood pressure before and after ACE were analyzed and compared. Results The level of pre-ACE blood pressure in the sham-operated group and CAS group was significantly higher than that in the normal group (P＜0.05). The level of post-ACE blood pressure was significantly increased in the normal group, sham-operated group and ACE group, and significantly decreased in the nimodipine treatment group as compared with the level of pre-ACE one in these groups (P＜0.05). No significant differences were noted between the levels of pre-ACE and post-ACE blood pressure in the normal group, sham-operated group and ACE group (P＞0.05). The level of post-ACE blood pressure in rats treated with nimodipine was obviously decreased as compared with that in the ACE group (P＜0.05). Conclusion ACE could increase the level of blood pressure in carotid atherosclerotic rats and this effect might be lessoned by the administration of nimodipine.     

丰富环境对脑梗死大鼠学习记忆和海马区微血管密度的影响

目的 研究丰富环境对局灶性脑梗死大鼠学习记忆及海马区微血管密度的影响.方法 采用开颅电凝法制作SD大鼠右侧大脑中动脉缺血(MCAO)模型,术后24h随机分为丰富环境组(EE组)和标准环境组(SE组),另设假手术组(Sham组),不电凝大脑中动脉,其余步骤与手术组相同.分别于术后7d、28d进行Mornis水迷宫测试大鼠学习记忆能力;以免疫组织化学法测定海马区微血管密度.结果 在学习记忆能力上,EE组成绩明显优于SE组(P<0.01),与Sham组相比无显著性差异(P>0.05);缺血侧海马区微血管密度显示EE组在术后14d、28d明显高于SE组大鼠(P<0.05),与Sham组相比无显著性差异(P>0.05).结论 丰富环境可促进脑梗死大鼠学习记忆能力的恢复与海马区微血管新生,改善大鼠的预后.

Abstract：

Objective To evaluate the effect of enriched environment on learning and memory and microvessel density in hippocampus of rats after unilateral local cerebral infarction. Methods The right middle cerebral artery occlusion (MCAO) was performed with electric coagulation in SD rats, then the rats were randomly divided into enriched environment stimulation group (EE group) and standard environment stimulation group (SE group). The sham-operation rats were as control group. On 7d and 28d, Morris water maze was used to evaluate the learning and memory ability;microvessel density in hippocampus of rats was measured in the boundary zone to brain infarction on 1d,3d,7d,14d and 28d. Result The learning and memory ability in EE group was significantly better than that in SE group ( P < 0.01 ) and there was no significant difference between EE group and Sham group (P > 0.05 ) ;Compared with SE group, the microvessel density (MVD) of EE group in hippocampus of rats significantly increased on 14d and 28d after MCAO( P <0.05). There was no significant difference in MVD between EE group and sham group (P > 0.05 ). Conclusion The enriched environment can enhance the ability of learning and memory and promote the blood vessel proliferation of rats with unilateral local cerebral infarction.The study suggests enriched environment is good for recovery from brain damage in rats with MCAO.     

癫痫细胞悬液对海马干细胞分化的影响

Objective To investigate the effect of suspended cells from the hippocampus of epileptic rats on the differentiation of hippocampal stem cells.Methods Eight groups, including control group,glutamic acid groups (5 and 25 μmol/mL groups),normal hippocampal cells and epileptic cells groups (20 and 40 μmol/mL groups,respectively) were chosen in the experiment.The suspended cells were extracted from the hippocampus of epileptic rats and normal rats,and corresponding dose of them were added into the epileptic cells groups and normal hippocampal cells groups,respectively.Five μmol/mL and 25 μmol/mL glutamic acid were added into the glutamic acid groups,respectively.The vitality of differentiated stem cells was detected and compared with MTT method.Results MTT value (the vitality of differentiated stem cells) was increased following the increased differentiation time.Cell viability in the glutamic acid groups and normal hippocampal cells groups was slightly decreased as compared with that in the control group (P>0.05).The cell viability in the epileptic cells groups was slightly increased as compared with that in the control group (P>0.05).The MTT value in the epileptic cells group and the normal hippocampal cells group was not obviously different (P>0.05).Conclusion The suspended cells from the hippocampus of epileptic rats do not affect the differentiation of the hippocampal stem cells.     

戊四氮点燃慢性癫痫大鼠海马及颞叶皮质γ-氨基丁酸转运体1及胶质纤维酸性蛋白的表达

BACKGROUND： Gamma-aminobutyric acid transporter plays an important role in gamma-aminobutyric acid metabolism, and is highly associated with epilepsy seizures. Pathologically, astrocytes release active substances that alter neuronal excitability, and it has been demonstrated that astrocytes play a role in epileptic seizures. OBJECTIVE： To observe changes in gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression in the hippocampus and cortex of the temporal lobe in rats with pentylenetetrazol-induced chronic epilepsy. DESIGN, TIME AND SETTING： Randomized, controlled, animal experiment was performed at the Department of Neurobiology, Third Military University of Chinese PLA between January 2006 and December 2007. MATERIALS： Pentylenetetrazol was purchased from Sigma, USA; rabbit anti-rat gammaaminobutyric acid transporter 1 and glial fibrillary acidic protein were from Chemicon, USA. METHODS： A total of 40 Sprague Dawley rats were divided into model and control groups. Rat models of chronic epilepsy were created by pentylenetetrazol kindling, and were subdivided into 3-, 7-, and 14-day kindling subgroups. MAIN OUTCOME MEASURES： Gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression, as well as the number of positive cells in the hippocampus and cortex of temporal lobe of rats, were determined by immunohistochemistry and Western blot analyses. RESULTS： Compared with the control group, the number of gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein -positive cells in the hippocampus and cortex of rats with pentylenetetrazol-induced epilepsy significantly increased, gamma-aminobutyric acid transporter 1 and glial fibrillary acidic protein expression increased after 3 days of kindling, reached a peak on day 7, and remained at elevated levels at day 14 （P〈 0.05）. CONCLUSION： Astrocytic activation and gamma-aminobutyric acid transporter 1 overexpression may contribute to pentylenetetrazol-induced epilepsy.     

癫痫细胞悬液对海马干细胞分化的影响

Objective To investigate the effect of suspended cells from the hippocampus of epileptic rats on the differentiation of hippocampal stem cells.Methods Eight groups, including control group,glutamic acid groups (5 and 25 μmol/mL groups),normal hippocampal cells and epileptic cells groups (20 and 40 μmol/mL groups,respectively) were chosen in the experiment.The suspended cells were extracted from the hippocampus of epileptic rats and normal rats,and corresponding dose of them were added into the epileptic cells groups and normal hippocampal cells groups,respectively.Five μmol/mL and 25 μmol/mL glutamic acid were added into the glutamic acid groups,respectively.The vitality of differentiated stem cells was detected and compared with MTT method.Results MTT value (the vitality of differentiated stem cells) was increased following the increased differentiation time.Cell viability in the glutamic acid groups and normal hippocampal cells groups was slightly decreased as compared with that in the control group (P>0.05).The cell viability in the epileptic cells groups was slightly increased as compared with that in the control group (P>0.05).The MTT value in the epileptic cells group and the normal hippocampal cells group was not obviously different (P>0.05).Conclusion The suspended cells from the hippocampus of epileptic rats do not affect the differentiation of the hippocampal stem cells.     

Increased expression of Notch1 in temporal lobe epilepsy: animal models and clinical evidence

Temporal lobe epilepsy is associated with astrogliosis. Notchl signaling can induce astrogliosis in glioma. However, it remains unknown whether Notchl signaling is involved in the pathogenesis of epilepsy. This study investigated the presence of Notchl, hairy and enhancer of split-l, and glial fibrillary acidic protein in the temporal neocortex and hippocampus of lithium-pilocar- pine-treated rats. The presence of Notchl and hairy and enhancer of split-1 was also explored in brain tissues of patients with intractable temporal lobe epilepsy. Quantitative electroencephalo- gram analysis and behavioral observations were used as auxiliary measures. Results revealed that the presence of Notchl, hairy and enhancer of split-l, and glial fibriUary acidic protein were en- hanced in status epilepticus and vehicle-treated spontaneous recurrent seizures rats, but remain unchanged in the following groups： control, absence of either status epilepticus or spontaneous recurrent seizures, and zileuton-treated spontaneous recurrent seizures. Compared with patient control cases, the presences of Notch1 and hairy and enhancer of split- 1 were upregulated in the temporal neocortex of patients with intractable temporal lobe epilepsy. Therefore, these results suggest that Notchl signaling may play an important role in the onset of temporal lobe epilepsy via astrogliosis. Furthermore, zileuton may be a potential therapeutic strategy for temporal lobe epilepsy by blocking Notchl signaling.     

Effects of Ganoderma lucidum spore powder on astrocyte expression and glutamine synthetase activity in the hippocampal region of epileptic rats

BACKGROUND： Recent studies have demonstrated that astrocyte dysfunction plays a central role in inhibiting epileptic seizures and that regulation of astrocyte function may be a new target for treatment of epilepsy. OBJECTIVE： To observe the effects of Ganoderma lucidum spore powder （GLSP） on astrocyte morphology and glutamine synthetase （COS） activity in the hippocampal region of epileptic rats. DESIGN, TIME AND SETTING： A randomized, controlled animal experiment was performed at the Function Laboratory, College of Basic Medicine, Jiamusi University between October and December 2006. MATERIALS： A total of 30 Sprague Dawley （SD） rats were randomized to three groups （n = 10）： control, model, and GLSP. GLSP was sourced from Jiamusi Wild Ganoderma Lucidum Planting Base and prepared to 30 g/L with physiological saline before use. Pentylenetetrazol （PTZ） （10 g/L） was provided by Sigma Company, USA. METHODS： The control group received intraperitoneal （i.p.） and intragastric （i.g.） physiological saline. Following epilepsy induction by i.p. administration of PTZ （35 mg/kg）, rats from the mode/and GLSP groups were ig injected with physiological saline and GLSP （300 mg/kg）, respectively. Each compound was administered once per day, for a total of 28 successive days. Epileptic seizure convulsions were graded 0-5. A higher grade indicated more severe epilepsy. Only those rats showing stage 2 or higher convulsions at least 5 times successively were included in further experiments. MAIN OUTCOME MEASURES： Immediately alter injection, seizure activity was monitored for 30 minutes to determine the latent period and seizure duration; simultaneously, astrocyte numbers and GS activity in the hippocampal region of rats with epilepsy were detected by immunohistochemistry. RESULTS： All 30 rats were included in the final analysis. On day 28, following PTZ administration epileptic seizures were not found in the control group. In the GLSP group, rats exhibited rhythmic head nodding or     

戊四氮点燃过程中大鼠海马胶质细胞增生和突触重建的研究

目的探讨戊四氮点燃过程中海马胶质细胞增生及突触重建与慢性癫痫发病机制的关系。方法大鼠随机分为对照组、非药物干预组(戊四氮35mg/kg,腹腔注射,每日一次)和药物干预组(苯巴比妥30mg/kg,戊四氮35mg/kg,均为腹腔注射,每日一次)。采用免疫组织化学方法观察胶质原纤维酸性蛋白(GFAP)和神经细胞粘附分子(NCAM)表达水平。结果非药物干预组大鼠注射戊四氮后在行为学未出现惊厥,脑电图未出现痫性放电的点燃前潜伏期内,出现突触重建和胶质细胞增生,以海马CA3区、门区明显,与对照组比较,有显著性差异(P<0.05);与药物干预组对应时间点比较,亦有显著性差异(P<0.05)。结论大鼠注射戊四氮后引起反应性胶质细胞增生和神经元可塑性改变,可能与形成异常神经元放电环路,最终诱发癫痫发作有关,苯巴比妥可抑制异常神经网络的建立,预防癫痫发生。     

托吡酯对慢性癫痫幼鼠神经元保护作用的实验研究

目的 研究托吡酯(TPM)单药对慢性癫痫幼鼠损伤神经元的影响.方法 将3～4周龄雄性Wistar大鼠72只采用随机数字表法分为6组,每组各12只,A组:阴性对照组;B组:阳性对照组;C组:TPM低剂量组(20 mg/kg);D组:TPM中等剂量组(40 mg/kg);E组:TPM高剂量组(80 mg/kg);F组:合药组(TPM 40 mg/kg+丙戊酸钠200 mg/kg),其中B～F组为慢性癫痫组,于给药前腹腔注射戊四氮.连续用药2个月,观察幼鼠体重、行为学表现、血清神经元特异性烯醇化酶(NSE)及病理改变.结果 (1)E组对幼鼠体重的影响比C组、F组显著.(2)D组、E组戊四氮诱发痫性发作的时间延长,痫性发作的程度减轻.(3)TPM各剂量组NSE水平显著低于B组,F组与TPM单药组无差异.(4)E组海马组织神经元的退行性变和胶质细胞的增生程度减轻明显.结论 TPM可减轻幼鼠痫性发作后的神经损伤程度,且存在剂量效应,但与丙戊酸钠联合可削弱其神经保护作用.     

尼莫地平对戊四氮慢性点燃癫痫大鼠行为及脑电图的影响

目的:探讨尼莫地平(nimodipine,NIM)对戊四氮(Pentylenetetrazole,PTZ)慢性点燃癫痫大鼠行为及脑电图的影响。方法:64只动物随机分为正常对照组(A组)、PTZ单纯致痫组(B组)、NIM1.25mg/kg干预组(C组)、NIM2.5mg/kg干预组(D组),通过腹腔注射PTZ建立慢性癫痫动物模型,观察大鼠行为、脑电图及海马组织学改变。结果:腹腔注射NIM可以明显抑制大鼠的痫性放电,减小其痫性发作级别,与正常对照组相比重型发作率明显降低(P<0.01),此外,NIM还能减轻海马的损伤程度。结论:NIM在PTZ慢性点燃癫痫大鼠模型中不仅具有抗惊厥作用,还能减轻海马的损伤程度。     

雷帕霉素对未成年癫痫模型大鼠的毒性作用

目的利用戊四氮(pentylenetetrazol,PTZ)慢性点燃Sprague Dawley大鼠(SD大鼠)模型观察在点燃初期腹腔注射雷帕霉素(rapamycin,RAPA)能否抑制癫痫发生以及雷帕霉素在治疗中的安全性。方法将6~8周龄SD雄性大鼠随机分为雷帕霉素干预组PTZ+RAPA及其对照组PTZ+NS(normal saline)及NS组,观察1周(w)、2周(w)、4周(w)、6周(w)共4个时间点,每亚组12只,观察实验动物体质量的变化、死亡率及癫痫发作情况。结果各组实验大鼠的死亡率:PTZ+RAPA组为22.9%,PTZ+NS组为10.4%,NS组为0%。PTZ+RAPA组与PTZ+NS组各个相对应的时间点(1 w,2 w,4 w,6 w)体质量差均有统计学差异(P0.001)。6周时PTZ+RAPA组的点燃率为66.7%,PTZ+NS组的点燃率为58.3%,二者无统计学差异(P0.05)。PTZ+RAPA组与PTZ+NS组相对应时间点(1 w,2 w,4 w,6 w)发作分值的两两比较差异无统计学意义(P0.05)。结论雷帕霉素未能减少或抑制未成年大鼠的癫痫发作,但能明显降低未成年SD大鼠的体质量,可能有一定的毒副作用。     

戊四氮点燃癫痫持续状态大鼠海马p53的表达

目的观察癫痫持续状态后不同时间的大鼠海马神经细胞p5的表达变化,探讨p53基因在癫痫发作后的凋亡调控机制。方法戊四氮腹腔注射诱导大鼠癫痫持续状态（SE）,观察大鼠行为学改变,并选取SE后1、6、24、48、72h共5个时间点运用反转录多聚酶链反应（RT—PCR）、Western Blot方法检测SE组和对照组大鼠海马p53的表达。结果SE后6h,p53表达开始增高（P〈0．05）,24h达高峰（P〈0．001）,48h略有下降（P〈0．05）,72h后下降明显（P〈0．01）,但仍高于对照组水平。各组间两两比较差异有统计学意义（P〈0．05）。结论p53基因对戊四氮诱导癫痫持续状态后大鼠神经细胞凋亡起重要作用。     

丙戊酸钠对戊四氮致痫大鼠海马神经元凋亡的影响

目的 探讨丙戊酸钠(VAP)对戊四氮(PTZ)致痫大鼠海马神经元凋亡的影响.方法 将48只成年Wistar大鼠随机平均分为正常对照(NC)组、PTZ组和VAP组,PTZ组和VAP组大鼠腹腔注射阈下剂量的PTZ 35mg/(kg·d),直至达到点燃标准.点燃后,VAP组大鼠经腹腔注入VAP15mg/(kg·d),PTZ组大鼠经腹腔注入生理盐水,30min后,再腹腔注射PTZ诱发癫痫发作.应用免疫组化法检测大鼠海马神经元Fas、Caspase-3和Survivin的表达.结果 PTZ组大鼠海马神经元Fas、Caspase-3阳性细胞数和光密度明显高于VAP组和NC组(均P<0.01),Survivin阳性细胞数和光密度明显低于VAP组(P<0.01),但高于NC组(P<0.05);VAP组大鼠海马神经元Fas、Caspase-3阳性细胞数和光密度明显高于NC组(均P<0.05),Survivin阳性细胞数和光密度明显高于NC组(P<0.01).结论 癫痫发作可以导致大鼠海马神经元的凋亡,而丙戊酸钠有对抗癫痫发作导致细胞凋亡的作用,主要通过促进Survivin的表达和抑制Fas和Caspase-3的表达发挥作用.     

Let-7c-1对戊四氮致痫大鼠学习记忆功能的作用

目的研究let-7c-1对戊四氮(pentylenetetrazol,PTZ)致痫大鼠学习记忆功能的影响,探讨其可能机制。方法通过PTZ腹腔注射SD雄性大鼠建立慢性癫痫模型,随机分为癫痫组、干预对照组、let-7c-1激动剂组,各组12只,另设12只大鼠为正常组。28 d后,观察各组大鼠的行为学变化,let-7c-1基因表达及大鼠海马组织中Bcl-2、Caspase3蛋白的表达。结果与正常组相比,癫痫组大鼠逃避潜伏期延长、穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P0.05);癫痫组与干预对照组相比,逃避潜伏期、穿越平台次数、在目标象限的总路程无统计学差异(P0.05);与干预对照组相比,let-7c-1激动剂组逃避潜伏期明显延长,穿越平台次数减少、在目标象限的总路程缩短,差异有统计学意义(P0.05)。干预对照组与let-7c-1激动剂组let-7c-1基因相对表达量分别为(1.35±0.32)、(62.53±21.01)(F=50.97,P0.05)。癫痫组let-7c-1基因表达量高于正常组,差异有统计学意义(P0.05)。let-7c-1激动剂组let-7c-1基因表达量明显高于干预对照组、癫痫组及正常组,差异有统计学意义(P0.05)。与正常组相比,癫痫组的Bcl-2蛋白表达减少,Caspase3蛋白表达增加,差异有统计学意义(P0.05);癫痫组与干预对照组相比,Bcl-2蛋白及Caspase3蛋白的表达无统计学差异(P0.05)。与干预对照组相比,let-7c-1激动剂组Bcl-2蛋白表达明显减少,Caspase3蛋白表达明显增加,差异有统计学意义(P0.05)。结论 Let-7c-1可能通过减少海马组织Bcl-2蛋白及增加Caspase-3蛋白表达使PTZ致痫大鼠的学习记忆功能受损。     

Assessment of seizure susceptibility in pilocarpine epileptic and nonepileptic Wistar rats and of seizure reinduction with pentylenetetrazole and electroshock models

Purpose:   Pentylenetetrazole (PTZ) and maximal electroshock (MES) models are often used to induce seizures in nonepileptic control animals or naive animals. Despite being widely used to screen antiepileptic drugs (AEDs), both models have so far failed to detect potentially useful AEDs for treating drug-resistant epilepsies. Here we investigated whether the acute induction of MES and PTZ seizures in epileptic rats might yield a distinct screening profile for AEDs.
Methods:   Status epilepticus (SE) was induced in adult male Wistar rats by intraperitoneal pilocarpine injection (Pilo, 320 mg/kg, i.p.). One month later, controls or naive animals (Cont) that did not develop SE postpilocarpine (N-Epi) and pilocarpine-epileptic rats (Epi) received one of the following: phenobarbital (PB, 40 mg/kg), phenytoin (PHT, 50 mg/kg), or valproic acid (VPA, 400 mg/kg). Thirty min later the animals were challenged with either subcutaneous MES or PTZ (50 mg/kg, s.c.).
Results:   VPA, PB, and PHT were able to prevent MES in all groups tested (Cont, N-Epi, and Epi groups), whereas for the PTZ model, only the Cont group (naive animals) had seizure control with the same AEDs. In addition, Epi and N-Epi groups when challenged with PTZ exhibited a higher incidence of severe seizures (scores IV-IX) and SE (p   <   0.05, Fisher's exact test).
Conclusions:   Our findings suggest that the induction of acute seizures with PTZ, but not with MES, in animals pretreated with pilocarpine (regardless of SE induction) might constitute an effective and valuable method to screen AEDs and to study mechanisms involved in pharmacoresistant temporal lobe epilepsy (TLE).     

Parenteral magnesium sulfate fails to control electroshock and pentylenetetrazol seizures in mice

Magnesium sulfate has been used as an anticonvulsant in the treatment of eclampsia, but efficacy of magnesium in other types of seizure disorders is poorly documented. We examined the effects of magnesium sulfate (MgSO4) on seizures produced in mice by maximal electroshock (MES) and pentylenetetrazol (PTZ), MgSO4 injection (6.7 mEq/kg i.p.) caused weakness in all animals. With suprathreshold electroshock, 10/10 controls and 11/12 treated animals had seizures with tonic hind limb extension (P = NS). Electroshock threshold was unaltered by magnesium treatment (n = 48; P = 0.47). PTZ induced clonic seizures in 12/12 controls and 5/14 treated animals (P less than 0.05). This difference was likely due to muscular weakness because frequency of EEG spikes was the same in PTZ and PTZ + MgSO4 groups. Mean serum magnesium levels were 2.3 +/- 0.3 mEq/l in animals not given MgSO4; 10.9 +/- 1.4 mEq/l and 12.8 +/- 2.2 mEq/l in treated animals with and without seizures (P = NS). We conclude that magnesium sulfate had no significant anticonvulsant activity in mouse MES and PTZ models for epilepsy. The relevance of these findings to the possible efficacy of magnesium sulfate in eclamptic seizures and other types of epilepsy remains to be determined.