本文選題：小兒 + 驚厥　； 參考：《第四軍醫(yī)大學》2016年碩士論文

【摘要】：驚厥在小兒時期普遍常見,有較高的發(fā)病率。多種不同的致病因素引起神經系統(tǒng)功能紊亂,神經元異常放電,可發(fā)為驚厥。小兒神經系統(tǒng)處于發(fā)育階段,驚厥發(fā)作易損傷神經元而對患兒產生短期或長期的不良影響。用西醫(yī)的方法治療小兒驚厥,當前最常用的藥物為苯巴比妥(Phenobarbital,PB),但有證據(jù)表明PB能引起動物神經凋亡,關于PB的長期神經發(fā)育副作用也已被證實。而中醫(yī)藥根據(jù)個體差異,通過辨證論治的方法,根據(jù)不同證型、不同伴發(fā)癥狀來治療小兒驚厥,能使患兒癥狀得到明顯緩解,且中藥毒副作用少,可長期服用。已有臨床研究證實,用中醫(yī)藥或中西醫(yī)結合的方法治療小兒驚厥,不僅能提高療效,而且能減少不良反應。本研究系統(tǒng)分析中醫(yī)藥或在常規(guī)西醫(yī)治療基礎上加用中醫(yī)藥治療小兒驚厥的療效和復發(fā)情況,為臨床進一步運用中醫(yī)藥治療小兒驚厥提供循證依據(jù);選擇鎮(zhèn)驚安神類中藥之一琥珀為研究對象,取其主要活性成分琥珀酸(Succinic acid,SA),通過觀察SA對驚厥幼鼠小腦浦肯野細胞(Purkinje cell,PC)電生理功能(主要觀察PC興奮性及其突觸可塑性)的近遠期影響,并探討其產生的機制,從而為琥珀酸更安全地應用于臨床提供實驗證據(jù),為繼續(xù)開發(fā)安全有效的治療小兒驚厥之中藥提供實驗思路及方法。一、中醫(yī)藥治療小兒驚厥的系統(tǒng)評價目的評價中醫(yī)藥治療小兒驚厥的療效與預后效果。方法在計算機網絡中輸入關鍵詞,檢索1995~2015年關于中醫(yī)藥治療小兒驚厥的文獻,檢索的文獻庫有PUBMED、MEDLINE、Embase、維普期刊數(shù)據(jù)庫、萬方數(shù)據(jù)庫、Cochrane Library臨床對照試驗資料庫、中國生物醫(yī)學文獻數(shù)據(jù)庫、中國優(yōu)秀博碩學位論文全文數(shù)據(jù)庫、中文期刊網全文數(shù)據(jù)庫,手工檢索有關的兒科相關中文雜志、中醫(yī)兒科相關中文雜志、學術會議論文、所納入文獻的參考文獻。依據(jù)Jadad量表,對納入的關于中藥治療小兒驚厥的臨床隨機對照試驗進行質量評價和數(shù)據(jù)提取。采用Review Manager5.3軟件對數(shù)據(jù)進行meta分析。結果共納入49篇文獻,在小兒驚厥的治療中均有中醫(yī)藥療法體現(xiàn)并采用隨機對照方法,共4228例患者。治療組的治療方法為單用中醫(yī)藥(4篇文獻)或在常規(guī)西醫(yī)治療基礎上加用中醫(yī)藥(45篇文獻),對照組的治療方法均為常規(guī)西醫(yī)治療。36篇文獻對治療效果有統(tǒng)計,25篇文獻對治療后的復發(fā)情況有統(tǒng)計。Meta分析結果顯示:中醫(yī)藥治療小兒驚厥相比于常規(guī)西醫(yī)治療,治療效果明顯提高(OR 4.34,95%CI[3.42,5.50]),復發(fā)率明顯降低(OR 0.30,95%CI[0.24,0.37]),且差異有統(tǒng)計學意義。結論中醫(yī)藥治療小兒驚厥能提高治療效果并降低驚厥復發(fā)率。二、琥珀酸腦保護作用的實驗研究目的研究琥珀酸對驚厥幼鼠小腦PC電生理功能的保護作用。方法健康新生7天(P7)的SD幼鼠隨機分為新生期組(用藥30min后取小腦)和發(fā)育期組(養(yǎng)至30天后取小腦),新生期組和發(fā)育期組再各分為以下6組:正常對照組(control組)、驚厥模型組(seizure組)、30mg/Kg PB組、30mg/Kg SA組、120mg/Kg PB組、120mg/Kg SA組。采用全細胞膜片鉗技術,用不同電流強度刺激每組SD鼠小腦腦組織切片的PC,誘發(fā)產生動作電位(Action Potential,AP),并記錄下來;刺激平行纖維,誘發(fā)PC產生興奮性突觸后電流(Excitatory postsynaptic current,EPSC),記錄下其長時程抑制(Long term depression,LTD)現(xiàn)象。結果新生期和發(fā)育期驚厥模型組幼鼠PC動作電位頻率均較正常對照組明顯增高(P0.05),PC LTD均較正常對照組明顯增強(P0.05)。120 mg/Kg PB組PC動作電位閾刺激較正常對照組明顯降低(P0.05),動作電位頻率較正常對照組明顯增高(P0.05),PC LTD較驚厥模型組進一步增強(P0.05)。新生期及發(fā)育期120mg/kg SA組PC動作電位的頻率均顯著低于驚厥模型組(P0.05),而接近正常對照組(P0.05),發(fā)育期30mg/kg SA組和120mg/kg SA組PC的閾刺激與驚厥模型組相比均明顯增高(P0.05),新生期與發(fā)育期30mg/kg SA組和120mg/kg SA組EPSC幅值的抑制程度均明顯小于驚厥模型組(P0.05),接近正常對照組(P0.05)。結論新生期驚厥幼鼠小腦PC興奮性增高,PF-PC突觸可塑性發(fā)生異常改變,并持續(xù)至發(fā)育期,PB可使驚厥幼鼠小腦PC電生理功能受損加重,而SA不僅能夠降低驚厥引起的幼鼠小腦PC的高興奮性,而且能改善驚厥引起的幼鼠小腦PC突觸可塑性近遠期的異常。
[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.

【學位授予單位】：第四軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R272

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