中药治疗小儿惊厥的系统评价及琥珀酸脑保护作用的实验研究

发布时间：2018-05-10 17:10

本文选题：小儿 + 惊厥　；参考：《第四军医大学》2016年硕士论文

【摘要】：惊厥在小儿时期普遍常见,有较高的发病率。多种不同的致病因素引起神经系统功能紊乱,神经元异常放电,可发为惊厥。小儿神经系统处于发育阶段,惊厥发作易损伤神经元而对患儿产生短期或长期的不良影响。用西医的方法治疗小儿惊厥,当前最常用的药物为苯巴比妥(Phenobarbital,PB),但有证据表明PB能引起动物神经凋亡,关于PB的长期神经发育副作用也已被证实。而中医药根据个体差异,通过辨证论治的方法,根据不同证型、不同伴发症状来治疗小儿惊厥,能使患儿症状得到明显缓解,且中药毒副作用少,可长期服用。已有临床研究证实,用中医药或中西医结合的方法治疗小儿惊厥,不仅能提高疗效,而且能减少不良反应。本研究系统分析中医药或在常规西医治疗基础上加用中医药治疗小儿惊厥的疗效和复发情况,为临床进一步运用中医药治疗小儿惊厥提供循证依据;选择镇惊安神类中药之一琥珀为研究对象,取其主要活性成分琥珀酸(Succinic acid,SA),通过观察SA对惊厥幼鼠小脑浦肯野细胞(Purkinje cell,PC)电生理功能(主要观察PC兴奋性及其突触可塑性)的近远期影响,并探讨其产生的机制,从而为琥珀酸更安全地应用于临床提供实验证据,为继续开发安全有效的治疗小儿惊厥之中药提供实验思路及方法。一、中医药治疗小儿惊厥的系统评价目的评价中医药治疗小儿惊厥的疗效与预后效果。方法在计算机网络中输入关键词,检索1995~2015年关于中医药治疗小儿惊厥的文献,检索的文献库有PUBMED、MEDLINE、Embase、维普期刊数据库、万方数据库、Cochrane Library临床对照试验资料库、中国生物医学文献数据库、中国优秀博硕学位论文全文数据库、中文期刊网全文数据库,手工检索有关的儿科相关中文杂志、中医儿科相关中文杂志、学术会议论文、所纳入文献的参考文献。依据Jadad量表,对纳入的关于中药治疗小儿惊厥的临床随机对照试验进行质量评价和数据提取。采用Review Manager5.3软件对数据进行meta分析。结果共纳入49篇文献,在小儿惊厥的治疗中均有中医药疗法体现并采用随机对照方法,共4228例患者。治疗组的治疗方法为单用中医药(4篇文献)或在常规西医治疗基础上加用中医药(45篇文献),对照组的治疗方法均为常规西医治疗。36篇文献对治疗效果有统计,25篇文献对治疗后的复发情况有统计。Meta分析结果显示:中医药治疗小儿惊厥相比于常规西医治疗,治疗效果明显提高(OR 4.34,95%CI[3.42,5.50]),复发率明显降低(OR 0.30,95%CI[0.24,0.37]),且差异有统计学意义。结论中医药治疗小儿惊厥能提高治疗效果并降低惊厥复发率。二、琥珀酸脑保护作用的实验研究目的研究琥珀酸对惊厥幼鼠小脑PC电生理功能的保护作用。方法健康新生7天(P7)的SD幼鼠随机分为新生期组(用药30min后取小脑)和发育期组(养至30天后取小脑),新生期组和发育期组再各分为以下6组:正常对照组(control组)、惊厥模型组(seizure组)、30mg/Kg PB组、30mg/Kg SA组、120mg/Kg PB组、120mg/Kg SA组。采用全细胞膜片钳技术,用不同电流强度刺激每组SD鼠小脑脑组织切片的PC,诱发产生动作电位(Action Potential,AP),并记录下来;刺激平行纤维,诱发PC产生兴奋性突触后电流(Excitatory postsynaptic current,EPSC),记录下其长时程抑制(Long term depression,LTD)现象。结果新生期和发育期惊厥模型组幼鼠PC动作电位频率均较正常对照组明显增高(P0.05),PC LTD均较正常对照组明显增强(P0.05)。120 mg/Kg PB组PC动作电位阈刺激较正常对照组明显降低(P0.05),动作电位频率较正常对照组明显增高(P0.05),PC LTD较惊厥模型组进一步增强(P0.05)。新生期及发育期120mg/kg SA组PC动作电位的频率均显著低于惊厥模型组(P0.05),而接近正常对照组(P0.05),发育期30mg/kg SA组和120mg/kg SA组PC的阈刺激与惊厥模型组相比均明显增高(P0.05),新生期与发育期30mg/kg SA组和120mg/kg SA组EPSC幅值的抑制程度均明显小于惊厥模型组(P0.05),接近正常对照组(P0.05)。结论新生期惊厥幼鼠小脑PC兴奋性增高,PF-PC突触可塑性发生异常改变,并持续至发育期,PB可使惊厥幼鼠小脑PC电生理功能受损加重,而SA不仅能够降低惊厥引起的幼鼠小脑PC的高兴奋性,而且能改善惊厥引起的幼鼠小脑PC突触可塑性近远期的异常。
[Abstract]:Convulsions are common in children and have high incidence. Many different pathogenic factors cause nervous system dysfunction, abnormal discharge of neurons, and convulsions. The nervous system in children is at the developmental stage. The seizures can easily damage the neurons and produce short-term or long-term adverse effects on the children. The treatment of children with western medicine method is used in the treatment of children. Convulsion, the most commonly used drug is Phenobarbital (PB), but there is evidence that PB can cause nerve apoptosis in animals, and the long-term side effects of PB have also been confirmed. The symptoms have been relieved obviously, and the toxic and side effects of traditional Chinese medicine are few and can be taken for a long time. The clinical study has confirmed that the treatment of children with convulsion with traditional Chinese medicine or traditional Chinese and Western medicine can not only improve the curative effect, but also reduce the adverse reaction. In order to provide evidence based evidence for the further use of traditional Chinese medicine to treat infantile convulsions, one of the main active ingredients, succinic acid (Succinic acid, SA), was selected as the study object, and the electrophysiological functions of Purkinje cell (PC) in the cerebellum of convulsive rats were observed by SA (the main observation of PC). The effect of excitability and its synaptic plasticity and its mechanism are discussed, so as to provide experimental evidence for succinic acid more safely in clinical practice, and to provide experimental ideas and methods for the continued development of safe and effective Chinese medicine for the treatment of infantile convulsions. The curative effect and prognosis effect of infantile convulsion. Methods to enter the key words in computer network to retrieve the literature of 1995~2015 for the treatment of convulsion of children in traditional Chinese medicine. The retrieval literature library includes PUBMED, MEDLINE, Embase, VP journal database, Wanfang database, Cochrane Library clinical trial database, Chinese Biomedical Literature data. Library, the full text database of Chinese excellent master's degree thesis, the full text database of Chinese Journal Network, manual retrieval of relevant Chinese Journal of Pediatrics, Chinese Journal of Pediatrics related to Chinese medicine, academic conference papers, and references to the literature. According to the Jadad scale, the randomized controlled trial of the inclusion of traditional Chinese medicine in the treatment of children's convulsion was carried out. Review Manager5.3 software was used to carry out meta analysis of data. The results were included in 49 articles. In the treatment of infantile convulsions, there were traditional Chinese medicine therapy and random control method, with a total of 4228 patients. The treatment group was treated by only traditional Chinese medicine (4 Literature) or on the basis of conventional western medicine treatment. Combined with traditional Chinese medicine (45 Literature), the treatment methods of the control group were all the conventional western medicine treatment.36 literature for the treatment effect of the treatment, 25 literature on the recurrence of the treatment after the statistical analysis showed that: Chinese medicine treatment of children convulsions compared to conventional western medicine treatment, treatment effect was significantly improved (OR 4.34,95%CI[3.42,5.50]), recurrence The rate was significantly lower (OR 0.30,95%CI[0.24,0.37]), and the difference was statistically significant. Conclusion Chinese medicine treatment of children with convulsion can improve the effect of treatment and reduce the recurrence rate of convulsion. Two, the protective effect of succinic acid on the brain protection of the cerebellum of rats with succinic acid (succinic acid). Methods the effect of succinic acid on the electrophysiological function of PC in the cerebellum of the young rats. Method the SD of healthy newborn 7 days (P7) was SD The young rats were randomly divided into the new stage group (cerebellum after taking 30min after taking medicine) and the development period group (cerebellum after 30 days). The new stage group and the development group were divided into 6 groups: the normal control group (group control), the convulsive model group (Group seizure), the 30mg/Kg PB group, the 30mg/Kg SA group, the 120mg/Kg PB group, the 120mg/Kg SA group. The same current intensity stimulates the PC of the cerebellar brain tissue section of each group of SD rats and induces the action potential (Action Potential, AP) and records it; stimulates the parallel fibers to induce PC to produce excitatory postsynaptic currents (Excitatory postsynaptic current, EPSC), and records the long duration inhibition (Long term) phenomenon. The PC action potential frequency of young rats in the model group was significantly higher than that in the normal control group (P0.05), and the PC LTD was significantly higher than the normal control group (P0.05), the PC action potential threshold stimulation in.120 mg/Kg PB group was significantly lower than that of the normal control group (P0.05), and the action potential frequency was significantly higher than that in the normal control group (P0.05), PC consultants were compared with the convulsive model group. Bu Zengqiang (P0.05). The frequency of PC action potential in the 120mg/kg SA group was significantly lower than that of the convulsive model group (P0.05), but it was close to the normal control group (P0.05). The threshold stimulation of 30mg/kg SA group and 120mg/kg SA group was significantly higher than that of the convulsive model group (P0.05). The degree of inhibition of C amplitude was significantly less than that of the convulsive model group (P0.05), which was close to the normal control group (P0.05). Conclusion the cerebellar PC excitability of the newborn rats was increased, the PF-PC synaptic plasticity was abnormal and sustained to the developmental stage, and PB could aggravate the impairment of the electrophysiological function of the cerebellum PC in the juvenile rats, and SA not only could reduce the juvenile of the convulsion of the cerebellum, but not only can reduce the juvenile of convulsion. Rat cerebellum PC is hyperactive, and it can improve the near - and long-term abnormalities of PC synaptic plasticity in the cerebellum of rats.

【学位授予单位】：第四军医大学
【学位级别】：硕士
【学位授予年份】：2016
【分类号】：R272

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