穴位埋线抗癫痫的临床观察及对大鼠海马神经元凋亡影响的时效研究
|
摘要
癫痫(Epilepsy)是神经内科临床常见的慢性发作性疾病,因其反复发作性、发作突然性、复杂性等特点,故病程较长,治疗不易,给患者的日常工作、学习、生活以及身心健康带来了诸多压力,给社会增添了沉重的负担。临床治疗上,不但要早发现、早治疗,而且要控制癫痫发作,减少发作次数,延长发作间歇期,最终达到治愈。
尽管癫痫的发病机制仍未完全明确,抗痫药物的临床运用已取得了一定的疗效。但目前常规及大部分新型抗痫药物并不能完全控制所有痫性发作,且具有较大的毒、副作用,使癫痫病人在控制了癫痫症状之后,仍然要忍受随之而来的并发症、伴随症及心理、精神等诸多方面的痛苦。其他非药物治疗尚处在实验研究和临床试验阶段,且费用昂贵,难以得到推广普及。
针灸对各型癫痫的治疗优势体现在简便、无药物毒副作用方面。它通过疏通气血、熄风定惊、醒脑开窍以调和阴阳,安神定志。穴位埋线疗法是将羊肠线埋入穴位内,利用羊肠线对穴位的持续刺激作用发挥治疗疾病的方法。其疗效高、安全、简便、低廉。
一、临床观察
目的:观察埋线疗法治疗原发性全面发作型癫痫的临床疗效、对生活质量的影响等,规范操作规程,并对其临床疗效进行再评价。
方法:采取随机对照试验,对60例原发性全面发作型癫痫患者进行临床观察。将60例癫痫患者随机分为埋线组和对照组,每组30例。埋线组用改良埋线针在每个穴位中埋植1ml长3-0号医用铬制羊肠线。主穴:A.大椎、筋缩、丰隆_双,B.心俞_左、肝俞_左、阳陵泉_双,C.心俞_右、肝俞_右、臂臑_双,A、B、C三组主穴轮流取用,每次埋线加辨证配穴一个,配穴左右交替。每15天埋线1次,90天后观察疗效。对照组给予丙戊酸钠片按15mg/(kg.d)的剂量口服,用量超过250mg/d时,分次服用,每日清晨或早晨,中午2次服用,连服90天为一疗程。疗程结束后观察两组治疗前后的症状疗效、发作频率和生活质量评分。
结果
1.总疗效:两组治疗前后比较,治疗组总有效率76.7%,对照组总有效率86.7%,对照组优于治疗组,但经统计学分析,P=0016＞0.05,两者之间无统计学意义。
2.症状疗效:两组治疗前后比较,均有P＜0001,提示治疗组和对照组经治疗后,症状改善有统计学意义;治疗前,治疗组与对照组比较,t=0.54,P=0.59,说明两组治疗前症状轻重程度具有可比性;治疗后,治疗组与对照组比较,t=0.53,P=0.60,说明两组治疗后症状评分差异无统计学意义。
3.发作频率:治疗组与对照组在治疗3个月后、半年后、1年后发作频率与治疗前相比,均具有统计学意义。两组之间的比较,在治疗3个月后、半年后,发作频率均无统计学差异;在治疗1年后,对照组在发作频率方面明显优于治疗组。
4.生活质量改善:治疗组在治疗3个月后、半年后、1年后生活质量的改善均有统计学意义;而对照组在治疗3个月后生活质量无明显改善,在治疗半年后、1年后生活质量的改善才有统计学意义。在治疗3个月后、半年后、1年后,治疗组在改善生活质量方面优于对照组,均具有统计学意义。
结论:在总疗效上,包括症状评分、控制癫痫发作频率方面,穴位埋线疗法与药物治疗作用相仿,穴位埋线组未见有明显优势,但在改善患者生活质量方面,穴位埋线组显示了明显的优势作用。
二、动物实验
目的:动态观察埋线法对电点燃癫痫模型大鼠海马神经元凋亡及凋亡相关基因的影响。
方法:将104只健康纯系雄性SD大鼠,随机分成13组,每组8只:(1)对照组,(2)模型1d组,(3)模型4d组,(4)模型7d组,(5)模型10d组,(6)模型14d组,(7)埋线1d组,(8)埋线4d组,(9)埋线7d组,(10)埋线10d组,(11)埋线14d组,(12)二次埋线10d组,(13)二次埋线14d组。对照组植入电极,不予刺激;(2)～(13)组均为造模动物,以电点燃法造成慢性癫痫模型。假手术组大鼠不予治疗;所有埋线组(7～13组)大鼠均在电点燃癫痫模型造模成功后,选取穴位大椎、心俞透膈俞双,予以埋线治疗一次;二次埋线组(12～13组)大鼠在第一次埋线后第7天再行埋线治疗。观察各组大鼠造模前后及治疗前后的一般状态。1d组、4d组、7d组、10d组、14d组和假手术组大鼠分别在点燃1d、4d、7d、10d和14d后,用10%水合氯醛(400mg/kg)腹腔注射麻醉后,经4%多聚甲醛心脏灌注固定,断头取左侧大脑半球。采用HE染色光镜下观察、原位细胞凋亡检测法检测海马神经元凋亡情况,采用免疫组化法检测海马p~53、Bax、Bcl-2蛋白表达。
结果
1.动态观察大鼠一般状态的变化,提示埋线治疗有助癫痫发作后的一般状态恢复,以一周后的远期效果较为明显,一周后再行埋线治疗则疗效有所叠加。
2.模型组大鼠海马神经元凋亡及相关基因表达的动态变化结果提示:单侧电点燃癫痫模型大鼠的痫性“镜灶”侧海马神经元,在造模后4d内首先在P~(53)的促进作用下发生凋亡,4d后至14d内在Bc1-2和Bax的协同作用下,神经元凋亡受到抑制。
3.埋线组和二次埋线组大鼠海马神经元凋亡及相关基因表达的动态变化结果提示:埋线治疗在癫痫发作后的早期(4d内)可通过抑制促凋亡基因p~(53)蛋白表达、延缓其达峰值的时程,从而减缓神经元凋亡的发生,此作用在4d后减弱;埋线治疗抑制大鼠海马神经元凋亡的作用在癫痫发作后的中期(4d～10d)减弱,甚至在远期(10d～14d)出现促进凋亡的作用,可能是通过抑制Bax蛋白表达的下降、延长其降至低峰值的时程,促进Bax蛋白表达的回升的结果;在中远期(7d～14d)内予二次埋线治疗对该效应有续效叠加的作用。埋线治疗对单侧电点燃癫痫模型大鼠海马神经元Bc1-2蛋白表达无明显作用。
结论:
1.单侧电点燃癫痫模型大鼠的痫性“镜灶”侧海马神经元,在造模后4d内首先在p~(53)的促进作用下发生凋亡,4d后至14d内在Bc1-2和Bax的协同作用下,神经元凋亡受到抑制。发作后早期的大量神经元凋亡,导致大鼠生活质量的降低,影响疾病的恢复。发作后中远期神经元凋亡的抑制,使在发作中已受损的神经元得不到及时清除而成为再次发作的基础。如此形成恶性循环,最终导致痫性发放的反复发作,症状加重,生活质量日益下降。
2.埋线治疗在癫痫发作后的早期(4d内)可通过抑制促凋亡基因p53蛋白表达、延缓其达峰值的时程,减缓神经元凋亡的发生,保护神经元,避免出现大量不必要的神经元脱失,从而改善癫痫患者的症状。
3.埋线治疗通过抑制Bax蛋白表达的下降、延长其降至低峰值的时程,致使在癫痫发作后的中期(4d～10d)抑制大鼠海马神经元凋亡的作用减弱;继而通过促进Bax蛋白表达的回升,致使在癫痫发作后的远期(10d～14d)出现促进凋亡的作用。上述作用可诱导已受损的神经元发生凋亡,以形成良性循环,使癫痫发作程度降低、发作频率减少,生活质量得以提高。
4.在癫痫发作后的中期(7d～14d)内予二次埋线治疗对疗效有续效叠加的作用。由此可指导临床埋线法治疗癫痫的治疗间隔以控制在1～2周内为宜。
Epilepsy is very common in nervous system diseases.The seizure is so suddenly and complicatedly that make the disease a long course and hard to cure.It brings the patients much pressure on their lives,study and work,and often proves to be a tax upon the society.Early diagnosis and early treatment are very important to epilepsy.A successful treatment is based on controlling the seizure and reducing the frequency.
Though the mechanism of epilepsy hasn't been totally confirmed,the using of anti-epilepsy drugs(AEDs)has obtained a lot of effects.But the routine and new AEDs still cannot entirely control all kinds of the seizure,also have many serious side-effects.It makes the patients suffer from the complications after the seizure.Since the other non-drug treatments are still under studying, and they all are very expensive,it' s very hard to promote now.
The advantage of acupuncture treatment to epilepsy includes simplicity,with few side-effects.It coordinates the function of yinyang and tranquilizes by dredging the vital energy and blood,calming wind-syndrome and frightening, waking up the patient from unconsciousness.Acupoint catgut embedding therapy treats disease by utilizing persistence stimulating of the catgut to the acupoint.The therapy is efficient,safe,simple and cheap.
Clinical Observation:
Objective:To observe the effect of the acupoint catgut embedding therapy on epilepsy,study the effect on the quality of life(QOL).
Method:60 patients were randomly divided into 2 groups:ACET(acupoint catgut embedding therapy)group and control group,30 patients in each group.Patients in ACET-group were treated by embedding a 1ml long #3-0 catgut into the acupoints,which was prescribed and combined as:A.DU14,DUB,ST40;B.BL15, BL18,GB34;C.BL15,BL18,LI14.The main point formula-A/B/C was used by turns, with an auxiliary point each time.They were treated once in 2 weeks,lasting for 3 months.The control group was treated by valproic acid(VPA),15mg/ (kg·d),p.o.The treatment also lasted for 3 months.
Result:
1.Total effect:Comparing with pretreatment,the general effective rate of the ACET-group being 76.7%,and the control group being 86.7%.This trial showed both treatment to be effective and there was no statistically significant difference between them in their effect(P=0.16＞0.05).
2.Effect on the symptoms:Comparing with pretreatment,the symptomatic improvement of both groups were significantly obtained(P＜0.01)and there was no statistically significant difference between them in their effect (P=0.60＞0.05).
3.Frequency of the seizure:3 months,half year and 1 year after the treatment, comparing with pretreatment,the seizure frequency of both group were significantly reduced.There was no statistically significant difference between them in their effect after 3 months or half year,but the statistical comparison after 1 year was significant.
4.Improvement of QOL:3 months,half year and 1 year after the treatment, comparing with pretreatment,QOL improvement of ACET-group were significantly obtained.QOL of control group didn't improve after 3 months,since the improvement were significantly obtained after half year and 1 year.And at the time 3 months,half year and 1 year after the treatment,QOL improvement of ACET-group were significantly superior to control group.
Conclusion:The effect of AECT and AEDs is similar on the total effect, including the effect on the epileptic symptoms,frequency of the seizure.the But AECT is significantly superior to AEDs on the improvement of QOL.
Experimental Research:
Objective:To investigate the dynamic changes of the neuron apoptosis and correlative genes in hippocampus of kindling epileptic rats treated by the catgut embedding therapy on epilepsy.
Method:104 male SD rats are randomly divided into sham operation group,5 model groups(1d,4d,7d,10d,14d),5 ACET-groups(1d,4d,7d,10d,14d)and 2 twice-ACET-groups(10d,14d),8 rats in each group.Rats of model groups, ACET-groups and twice-ACET-groups were made the electric kindling epilepsy model,while sham operation group was received the implantation of the bipolar electrode only.ACET-groups and twice-ACET-groups were treated by ACET just after the kindling at DU14,BL15,BL17.twice-ACET-groups were treated again after 7 days.Common condition of the rats was observed.Rats of 1d-groups, 4d-groups,7d-groups,10d-groups and 14d-groups were killed respectively 1 day,4 days,7 days,10 days,14 days after the kindling and made the hippocampus sections.In all cases,the apoptosis,expression of P~(53),Bax and Bcl-2 were detected by terminal dUTP-mediated nick end labeling(TUNEL)and immunohistochemistry.
Result:
1.Observed the dynamic changes of the common condition of the rats,it suggested that ACET can help the kindling model rats to get well,the effect was significant after 7 days.To treat again after 7 days can also enhance the effect.
2.The dynamic changes of the the neuron apoptosis and correlative genes in hippocampus of model groups suggested that the neurons in contralateral hippocampus commenced apoptosis by the promotion of p~(53)in 4 days after kindling, then during 4 to 14 days,the apoptosis was inhibited by the coordination of Bcl-2 and Bax.
3.The dynamic changes of the the neuron apoptosis and correlative genes in hippocampus of ACET-groups and twice-ACET-groups suggested that ACET can slower the apoptosis by inhibiting p~(53)and prolong the ascending period of p~(53) in 4 days after the seizure,this effect would weaken after 4 days.ACET may inhibit the descending of Bax,prolong its descending period and then promote its expression,in order to weaken the inhibition of the apoptosis during 4 to 10 days after seizure and then promote the apoptosis during 10 to 14 days after.This effect of ACET can be enhanced after treating again within 7 to 14 days later.ACET had no significant effect on expression of Bcl-2 in hippocampus of the kindling model rats.
Conclusion:
1.the neurons in contralateral hippocampus of the kindling model rats commenced apoptosis by the promotion of p~(53)in 4 days after kindling,then during 4 to 14 days,the apoptosis was inhibited by the coordination of Bcl-2 and Bax.Neuron apoptosis early after the seizure will due to the decreasing of QOL and the interfering with the recovering.7 days after the seizure,the neuron apoptosis inhibited,so the encroached neuron bequeathed to become the cause of next seizure.In this way a vicious circle is set up which it is difficult to break.The seizure will occur frequently,the symptoms get worse, the QOL will decrease and decrease.
2.ACET can slower the apoptosis by inhibiting p~(53)and prolong the ascending period of p~(53)in 4 days after the seizure.It helps to protect the neurons, avoid the losing of neurons,and improve the symptoms.
3.ACET inhibit the descending of Bax,prolong its descending period andthen promote its expression,in order to weaken the inhibition of the apoptosis during 4 to 10 days after seizure and then promote the apoptosis during 10 to 14 days after.These effects may lead to the apoptosis of the encroached neuron,and set up a fine circle to reduce the seizure,decrease the frequency, improve the QOL finally.
4.This effect of ACET can be enhanced after treating again within 7 to 14 days later.It follows that we should treat by ACET clinically once in 1 to 2 weeks.
尽管癫痫的发病机制仍未完全明确,抗痫药物的临床运用已取得了一定的疗效。但目前常规及大部分新型抗痫药物并不能完全控制所有痫性发作,且具有较大的毒、副作用,使癫痫病人在控制了癫痫症状之后,仍然要忍受随之而来的并发症、伴随症及心理、精神等诸多方面的痛苦。其他非药物治疗尚处在实验研究和临床试验阶段,且费用昂贵,难以得到推广普及。
针灸对各型癫痫的治疗优势体现在简便、无药物毒副作用方面。它通过疏通气血、熄风定惊、醒脑开窍以调和阴阳,安神定志。穴位埋线疗法是将羊肠线埋入穴位内,利用羊肠线对穴位的持续刺激作用发挥治疗疾病的方法。其疗效高、安全、简便、低廉。
一、临床观察
目的:观察埋线疗法治疗原发性全面发作型癫痫的临床疗效、对生活质量的影响等,规范操作规程,并对其临床疗效进行再评价。
方法:采取随机对照试验,对60例原发性全面发作型癫痫患者进行临床观察。将60例癫痫患者随机分为埋线组和对照组,每组30例。埋线组用改良埋线针在每个穴位中埋植1ml长3-0号医用铬制羊肠线。主穴:A.大椎、筋缩、丰隆_双,B.心俞_左、肝俞_左、阳陵泉_双,C.心俞_右、肝俞_右、臂臑_双,A、B、C三组主穴轮流取用,每次埋线加辨证配穴一个,配穴左右交替。每15天埋线1次,90天后观察疗效。对照组给予丙戊酸钠片按15mg/(kg.d)的剂量口服,用量超过250mg/d时,分次服用,每日清晨或早晨,中午2次服用,连服90天为一疗程。疗程结束后观察两组治疗前后的症状疗效、发作频率和生活质量评分。
结果
1.总疗效:两组治疗前后比较,治疗组总有效率76.7%,对照组总有效率86.7%,对照组优于治疗组,但经统计学分析,P=0016＞0.05,两者之间无统计学意义。
2.症状疗效:两组治疗前后比较,均有P＜0001,提示治疗组和对照组经治疗后,症状改善有统计学意义;治疗前,治疗组与对照组比较,t=0.54,P=0.59,说明两组治疗前症状轻重程度具有可比性;治疗后,治疗组与对照组比较,t=0.53,P=0.60,说明两组治疗后症状评分差异无统计学意义。
3.发作频率:治疗组与对照组在治疗3个月后、半年后、1年后发作频率与治疗前相比,均具有统计学意义。两组之间的比较,在治疗3个月后、半年后,发作频率均无统计学差异;在治疗1年后,对照组在发作频率方面明显优于治疗组。
4.生活质量改善:治疗组在治疗3个月后、半年后、1年后生活质量的改善均有统计学意义;而对照组在治疗3个月后生活质量无明显改善,在治疗半年后、1年后生活质量的改善才有统计学意义。在治疗3个月后、半年后、1年后,治疗组在改善生活质量方面优于对照组,均具有统计学意义。
结论:在总疗效上,包括症状评分、控制癫痫发作频率方面,穴位埋线疗法与药物治疗作用相仿,穴位埋线组未见有明显优势,但在改善患者生活质量方面,穴位埋线组显示了明显的优势作用。
二、动物实验
目的:动态观察埋线法对电点燃癫痫模型大鼠海马神经元凋亡及凋亡相关基因的影响。
方法:将104只健康纯系雄性SD大鼠,随机分成13组,每组8只:(1)对照组,(2)模型1d组,(3)模型4d组,(4)模型7d组,(5)模型10d组,(6)模型14d组,(7)埋线1d组,(8)埋线4d组,(9)埋线7d组,(10)埋线10d组,(11)埋线14d组,(12)二次埋线10d组,(13)二次埋线14d组。对照组植入电极,不予刺激;(2)～(13)组均为造模动物,以电点燃法造成慢性癫痫模型。假手术组大鼠不予治疗;所有埋线组(7～13组)大鼠均在电点燃癫痫模型造模成功后,选取穴位大椎、心俞透膈俞双,予以埋线治疗一次;二次埋线组(12～13组)大鼠在第一次埋线后第7天再行埋线治疗。观察各组大鼠造模前后及治疗前后的一般状态。1d组、4d组、7d组、10d组、14d组和假手术组大鼠分别在点燃1d、4d、7d、10d和14d后,用10%水合氯醛(400mg/kg)腹腔注射麻醉后,经4%多聚甲醛心脏灌注固定,断头取左侧大脑半球。采用HE染色光镜下观察、原位细胞凋亡检测法检测海马神经元凋亡情况,采用免疫组化法检测海马p~53、Bax、Bcl-2蛋白表达。
结果
1.动态观察大鼠一般状态的变化,提示埋线治疗有助癫痫发作后的一般状态恢复,以一周后的远期效果较为明显,一周后再行埋线治疗则疗效有所叠加。
2.模型组大鼠海马神经元凋亡及相关基因表达的动态变化结果提示:单侧电点燃癫痫模型大鼠的痫性“镜灶”侧海马神经元,在造模后4d内首先在P~(53)的促进作用下发生凋亡,4d后至14d内在Bc1-2和Bax的协同作用下,神经元凋亡受到抑制。
3.埋线组和二次埋线组大鼠海马神经元凋亡及相关基因表达的动态变化结果提示:埋线治疗在癫痫发作后的早期(4d内)可通过抑制促凋亡基因p~(53)蛋白表达、延缓其达峰值的时程,从而减缓神经元凋亡的发生,此作用在4d后减弱;埋线治疗抑制大鼠海马神经元凋亡的作用在癫痫发作后的中期(4d～10d)减弱,甚至在远期(10d～14d)出现促进凋亡的作用,可能是通过抑制Bax蛋白表达的下降、延长其降至低峰值的时程,促进Bax蛋白表达的回升的结果;在中远期(7d～14d)内予二次埋线治疗对该效应有续效叠加的作用。埋线治疗对单侧电点燃癫痫模型大鼠海马神经元Bc1-2蛋白表达无明显作用。
结论:
1.单侧电点燃癫痫模型大鼠的痫性“镜灶”侧海马神经元,在造模后4d内首先在p~(53)的促进作用下发生凋亡,4d后至14d内在Bc1-2和Bax的协同作用下,神经元凋亡受到抑制。发作后早期的大量神经元凋亡,导致大鼠生活质量的降低,影响疾病的恢复。发作后中远期神经元凋亡的抑制,使在发作中已受损的神经元得不到及时清除而成为再次发作的基础。如此形成恶性循环,最终导致痫性发放的反复发作,症状加重,生活质量日益下降。
2.埋线治疗在癫痫发作后的早期(4d内)可通过抑制促凋亡基因p53蛋白表达、延缓其达峰值的时程,减缓神经元凋亡的发生,保护神经元,避免出现大量不必要的神经元脱失,从而改善癫痫患者的症状。
3.埋线治疗通过抑制Bax蛋白表达的下降、延长其降至低峰值的时程,致使在癫痫发作后的中期(4d～10d)抑制大鼠海马神经元凋亡的作用减弱;继而通过促进Bax蛋白表达的回升,致使在癫痫发作后的远期(10d～14d)出现促进凋亡的作用。上述作用可诱导已受损的神经元发生凋亡,以形成良性循环,使癫痫发作程度降低、发作频率减少,生活质量得以提高。
4.在癫痫发作后的中期(7d～14d)内予二次埋线治疗对疗效有续效叠加的作用。由此可指导临床埋线法治疗癫痫的治疗间隔以控制在1～2周内为宜。
Epilepsy is very common in nervous system diseases.The seizure is so suddenly and complicatedly that make the disease a long course and hard to cure.It brings the patients much pressure on their lives,study and work,and often proves to be a tax upon the society.Early diagnosis and early treatment are very important to epilepsy.A successful treatment is based on controlling the seizure and reducing the frequency.
Though the mechanism of epilepsy hasn't been totally confirmed,the using of anti-epilepsy drugs(AEDs)has obtained a lot of effects.But the routine and new AEDs still cannot entirely control all kinds of the seizure,also have many serious side-effects.It makes the patients suffer from the complications after the seizure.Since the other non-drug treatments are still under studying, and they all are very expensive,it' s very hard to promote now.
The advantage of acupuncture treatment to epilepsy includes simplicity,with few side-effects.It coordinates the function of yinyang and tranquilizes by dredging the vital energy and blood,calming wind-syndrome and frightening, waking up the patient from unconsciousness.Acupoint catgut embedding therapy treats disease by utilizing persistence stimulating of the catgut to the acupoint.The therapy is efficient,safe,simple and cheap.
Clinical Observation:
Objective:To observe the effect of the acupoint catgut embedding therapy on epilepsy,study the effect on the quality of life(QOL).
Method:60 patients were randomly divided into 2 groups:ACET(acupoint catgut embedding therapy)group and control group,30 patients in each group.Patients in ACET-group were treated by embedding a 1ml long #3-0 catgut into the acupoints,which was prescribed and combined as:A.DU14,DUB,ST40;B.BL15, BL18,GB34;C.BL15,BL18,LI14.The main point formula-A/B/C was used by turns, with an auxiliary point each time.They were treated once in 2 weeks,lasting for 3 months.The control group was treated by valproic acid(VPA),15mg/ (kg·d),p.o.The treatment also lasted for 3 months.
Result:
1.Total effect:Comparing with pretreatment,the general effective rate of the ACET-group being 76.7%,and the control group being 86.7%.This trial showed both treatment to be effective and there was no statistically significant difference between them in their effect(P=0.16＞0.05).
2.Effect on the symptoms:Comparing with pretreatment,the symptomatic improvement of both groups were significantly obtained(P＜0.01)and there was no statistically significant difference between them in their effect (P=0.60＞0.05).
3.Frequency of the seizure:3 months,half year and 1 year after the treatment, comparing with pretreatment,the seizure frequency of both group were significantly reduced.There was no statistically significant difference between them in their effect after 3 months or half year,but the statistical comparison after 1 year was significant.
4.Improvement of QOL:3 months,half year and 1 year after the treatment, comparing with pretreatment,QOL improvement of ACET-group were significantly obtained.QOL of control group didn't improve after 3 months,since the improvement were significantly obtained after half year and 1 year.And at the time 3 months,half year and 1 year after the treatment,QOL improvement of ACET-group were significantly superior to control group.
Conclusion:The effect of AECT and AEDs is similar on the total effect, including the effect on the epileptic symptoms,frequency of the seizure.the But AECT is significantly superior to AEDs on the improvement of QOL.
Experimental Research:
Objective:To investigate the dynamic changes of the neuron apoptosis and correlative genes in hippocampus of kindling epileptic rats treated by the catgut embedding therapy on epilepsy.
Method:104 male SD rats are randomly divided into sham operation group,5 model groups(1d,4d,7d,10d,14d),5 ACET-groups(1d,4d,7d,10d,14d)and 2 twice-ACET-groups(10d,14d),8 rats in each group.Rats of model groups, ACET-groups and twice-ACET-groups were made the electric kindling epilepsy model,while sham operation group was received the implantation of the bipolar electrode only.ACET-groups and twice-ACET-groups were treated by ACET just after the kindling at DU14,BL15,BL17.twice-ACET-groups were treated again after 7 days.Common condition of the rats was observed.Rats of 1d-groups, 4d-groups,7d-groups,10d-groups and 14d-groups were killed respectively 1 day,4 days,7 days,10 days,14 days after the kindling and made the hippocampus sections.In all cases,the apoptosis,expression of P~(53),Bax and Bcl-2 were detected by terminal dUTP-mediated nick end labeling(TUNEL)and immunohistochemistry.
Result:
1.Observed the dynamic changes of the common condition of the rats,it suggested that ACET can help the kindling model rats to get well,the effect was significant after 7 days.To treat again after 7 days can also enhance the effect.
2.The dynamic changes of the the neuron apoptosis and correlative genes in hippocampus of model groups suggested that the neurons in contralateral hippocampus commenced apoptosis by the promotion of p~(53)in 4 days after kindling, then during 4 to 14 days,the apoptosis was inhibited by the coordination of Bcl-2 and Bax.
3.The dynamic changes of the the neuron apoptosis and correlative genes in hippocampus of ACET-groups and twice-ACET-groups suggested that ACET can slower the apoptosis by inhibiting p~(53)and prolong the ascending period of p~(53) in 4 days after the seizure,this effect would weaken after 4 days.ACET may inhibit the descending of Bax,prolong its descending period and then promote its expression,in order to weaken the inhibition of the apoptosis during 4 to 10 days after seizure and then promote the apoptosis during 10 to 14 days after.This effect of ACET can be enhanced after treating again within 7 to 14 days later.ACET had no significant effect on expression of Bcl-2 in hippocampus of the kindling model rats.
Conclusion:
1.the neurons in contralateral hippocampus of the kindling model rats commenced apoptosis by the promotion of p~(53)in 4 days after kindling,then during 4 to 14 days,the apoptosis was inhibited by the coordination of Bcl-2 and Bax.Neuron apoptosis early after the seizure will due to the decreasing of QOL and the interfering with the recovering.7 days after the seizure,the neuron apoptosis inhibited,so the encroached neuron bequeathed to become the cause of next seizure.In this way a vicious circle is set up which it is difficult to break.The seizure will occur frequently,the symptoms get worse, the QOL will decrease and decrease.
2.ACET can slower the apoptosis by inhibiting p~(53)and prolong the ascending period of p~(53)in 4 days after the seizure.It helps to protect the neurons, avoid the losing of neurons,and improve the symptoms.
3.ACET inhibit the descending of Bax,prolong its descending period andthen promote its expression,in order to weaken the inhibition of the apoptosis during 4 to 10 days after seizure and then promote the apoptosis during 10 to 14 days after.These effects may lead to the apoptosis of the encroached neuron,and set up a fine circle to reduce the seizure,decrease the frequency, improve the QOL finally.
4.This effect of ACET can be enhanced after treating again within 7 to 14 days later.It follows that we should treat by ACET clinically once in 1 to 2 weeks.
引文
[1]吴逊.神经病学-癫痫和发作性疾病[M].北京:人民军医出版社,2001:9
[2]史玉泉.神经病学新理论与新技术[M].上海:上海科技教育出版社,1998:12
[3]罗云坚,刘茂才.神经科专病中医临床诊治[M].北京:人民卫生出版社,2000:10
[4]瞿治平,俞丽云.实用癫痫学[M].上海:上海医科大学出版社,1997
[5]孔峰.癫痫发作时的脑电图分析[J].河南医学研究,1997;6(2):142-144
[6]宋永建等.24小时动态脑电图对癫痫的诊断意义[J].临床脑电学杂志.1998;7(2):80一82
[7]许虹等.癫痫患者的脑电图与CT对比研究[J].临床脑电学杂志,1998;7(1):9-11
[8]陈淑兰等.不同年龄癫痫患者临床与头颅MRI改变的研究[J].中风与神经疾病杂志,1998:15(4):231-232
[9]马志海等.小儿癫痫SPECT脑血流显像与CT、MRI、EEG的对比分析[J].西北国防医学杂志,1997;18(1):10-11
[10]赵延祜.30例儿童癫痫脑血流灌注显像检查的临床意义[J].临床儿科杂志,1998:16(2):97
[11]赵传胜,高旭光.抗癫痫新药Topiramate[J].国外医学,神经病学神经外科学分册,1998;25(1):27-30
[12]Privitera M,et al.Neurology[M],1996:46:1678
[13]Meldrum BS,et al.3rd European Congress of Epileptology,1998 May Warsaw
[14]冯亚波,姚红.抗痫药物的致痫作用[J].国外医学,神经病学神经外科学分册。1999;26(4):169-171
[15]Baker GA,Smith DF,Dewey M,ET AL.The initial development of a health-related quality of life model as an outcome measure in epilepsy[J].Epilepsy Res,1993;16:65-81
[16]欧阳华,刘弋戈.抗癫痫药物不良反应分析[J].儿科药学杂志,2005;11(4):57-59
[17]张军强,赵红宁,王晓明.癫痫的非药物治疗研究现状[J].川北医学院学报,2007:22(4):383-386
[18]谭启富.立体定向放射外科与癫痫[J].功能性和立体定向神经外科杂志,1997;10(1):45-46
[19]Houseton TX.Physician's manual for the VNS therapy pulsemodd 102Generator[J].Cyberonics Inc,2002:9-15
[20]郑乃智.癫痫的基因治疗[J].医学研究通讯.1996;25(3):1-2
[21]Bergner M.Quality of life,health status,and clinical research[J].Med Care,1989,127(Supp1):S148-S156
[22]Laine C,Davidoff F.Patient-centered medicine.A professional evolution[J].JAMA,1996,275(2):152-156
[23]CramerJA,Perrine K,Devinsky O.et al.Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory[J].Epilepsia,1998,39(1):81-88
[24]Heroder M,Oun A,Haldre S,et al.Epilepsy in Estonia:a quality-of-life study[J].Epilepsia,2001,42(8):1061-1073
[25]Lam J,Rozsavolgyi M,Soos G,et al.Quality of life of patients with epilepsy(Hungarian survey)[J].Seizure,2001,lO(2):lO0-106
[26]Tortes X,Arroyo S,Araya S,et al.The Spanish Version of the Quality-of-Life in Epilepsy Inventory(QOLIE-31):translation,validity,and reliability[J].Epilepsia,1999,40(9):1299-1304
[27]Renfroe JB,Wheless JW.Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy[J].Neurology,2002,59(6 Suppl 4):S26-30
[28]Wiebe S,Matijevic S,Eliasziw M,et al.Clinically important change in quality of life in epilepsy[J].J Neurol Neurosurg Psychiatry,2002,73(2):116-120
[29]Birbeck GL,Hays RD,Cui x,et al.Seizure reduction and quality of life improvements in people with epilepsy[J].Epilepsia,2002,43(5):535-538
[30]Andelman F,Fried Ⅰ,NeufeldMY.Quality of life self-assessment as a function of lateralization of lesion in candidates for epilepsy surgery[J].Epilepsia,2001,42(4):549-555
[31]Kline LN,Rentz AM,Grace EM.Evaluating health-related quality of life outcomes in clinical trials of antiepileptic drug therapy[J].Epilepsia,1998,39(9):965-977
[32]任晓琳,梁平,刘雪琴.癫痫患者生活质量量表-31(中文版)的翻译及修订[J].解放军护理杂志,2003,20(4):99-101
[33]Colling JA,Perrine K,Life fulfillment in an epilepsy sample from The United States[J].Soc Sci Med,1995,40;1579-1584
[34]Cramer JA.Quality Of life assessment in clinicl pratice[J].Neurology.1999,53(2):S49-S52
[35]朱丹彤,肖波,谢光洁,等.成年癫痫病的的生活质量及其影响因素[J].中华神经科杂志,2002,35(3):139-141
[36]解新荣,徐江涛,王毅,等.特发性癫痫患者的生活质量[J].中国行为医学科学,2001,10(5):427-428
[37]赵萍,郭秀东,严文康.癫痫儿童的心理障碍及其干预[J].中国儿童保健杂志.2002,10(2):76-78
[38]华蓓苓,周长发,朱兴海.中医病证专辑·癫狂痫[M].北京:中医古籍出版社,1990 第二版:12
[39]许沛虎.中医脑病学[M].北京:中国医药科技出版社,1998;8:485-499
[40]孙怡,杨任民.实用中西医结合神经病学[M].北京:人民卫生出版社,1999:447-466
[41]张登本.中医神经精神病学[M].北京:中国医药科技出版社,2000:306-317
[42]黄斌.癫痫中西医论治[M].北京:人民卫生出版社,1999:23-88
[43]刘立公,顾杰.癫痫证的古代针灸特点探讨[J].针灸临床杂志,2000;16(1):1-2
[44]奚永江,等.《针灸大成》中俞穴功效的计算机分析[J].上海针灸杂志,1988;(2):36
[45]刘立公,等。八纲病证的取穴特点初探[J].上海中医药杂志,1993;(5):42
[46]徐笨人,葛书翰。针刺大椎穴治疗癫痫95例[J].中国针灸,1982;(2):4-5
[47]徐非.督脉穴埋线治疗癫痫60例临床观察[J].国医论坛,1999;74(2):34
[48]刘永久.“神四针”“顶三针”治疗癫痫25例[J].辽宁中医杂志,1994;21(3):137
[49]刘胜利.针刺治疗癫痫病22例体会[J].针灸临床杂志,1997;13(8):44
[50]彭光超.针灸治疗癫痫54例的疗效观察[J].江西中医药,1990;21(3):40
[51]谷世喆,夏勇,张洪林.针灸治疗癫痫27例[J].北京中医药大学学报,1998;(4):66
[52]王进才.“背三针”治疗癫痫500例临床观察[J]。河南中医,1997;17(1):37
[53]杨子雨.针刺大椎、腰奇穴治疗癫痫108例[J].针灸临床杂志,1996:12(7、8):84-85
[54]程好收.针灸配合中药治疗癫痫100例观察[J].中级医刊,1989;21(12):51
[55]孟兰成.针刺华佗夹脊治疗癫痫的临床观察[J].中医药研究,1994;(3):47
[56]张丹玲.治脑三穴诊治癫痫病62例体会[J].中医函授通讯,1991;(2):41
[57]刘德荣.针刺为主治疗原发性癫痫932例疗效观察[J].针灸临床杂志,1993;9(6):17-18
[58]戴海玉,卫海英,沈丽.挑针治疗癫痫32例临床观察[J].河北中医,2000;22(9):661-661
[59]孙仁平,吴峰,邱凤翱,等。小针刀拔罐加埋线治疗癫痫病i000例体会[J].中国针灸,1999;19(9):547-548
[60]况琼,邹德霖,喻晓梨,等。针药治疗癫痫40例临床观察[J].江西中医药,1996;27(6):74-74
[61]孙曙霞.针刺配合药物贴脐治疗癫痫48例[J].上海针灸杂志,1997;16(1):13
[62]王海亮.孙思邈治痫方法初探[J].针灸临床杂志,1997;13(8):57
[63]李桂初.灸家兔癫痫模型百会及会阴穴的实验观察[J].湖南中医杂志,1994;10(7):51
[64]张鲁豫.穴位穿线配合艾灸治疗癫痫13例[J].新中医,1995;27(1):34-35
[65]旷秋和.时令灯火灸治疗癫痫50例疗效观察[J].针灸临床杂志,2003;19(7):54-54
[66]李效芳,马志刚.头皮针治疗癫痫40例[J].中国针灸,2000;20(8):475-475
[67]史子玉.头针治疗癫痫98例疗效观察[J].中国针灸,1986;6(1):17
[68]许永迅.长针和头针为主治疗运动性癫痫[J].上海针灸杂志,1991;(3):16-17
[69]曹晓来.头针配合电针治疗癫痫的临床观察[J].安徽中医临床杂志,1996;8(1):45
[70]郑祖艳.头穴电针治疗癫痫42例疗效观察[J].中医药信息,2000;17(1):53
[71]张锦华.针灸加电治疗痫症22例[J].中国针灸,2003;23(9):517
[72]潘静,赵瑞芹,马建宏,等.耳穴治疗小儿癫痫疗效观察[J].河北医药,2004;26(4):322-322
[73]郭双健等.耳针治疗癫痫临床观察[J].针灸学报,1992;8(6):16
[74]郑作祯.三棱针刺长强穴治疗癫痫136例[J].浙江中医杂志,1995;30..(7):310
[75]高永波.火针与毫针结合治疗癫痫76例[J].针灸临床杂志,1997;13(12):24-25
[76]许永迅.长针和头针为主治疗运动性癫痫[J].上海针灸杂志,1991;10(3):16
[77]郭勤英,杜秋来,白锡三,等.点穴治疗癫痫小发作17例[J].浙江中医杂志,1993:28(12):545
[78]刘安然.灸大椎穴治验5则[J].安徽中医临床杂志,1998;(3):169
[79]李希希,张家维,赖新生.穴位埋线法治疗癫痫的临床研究[J].广州中医药大学学报,1997:14(3):167-i68
[80]王兆荣.吴茱萸贴敷穴位治疗癫痫病[J].江西中医药,1997;(2):61
[81]王海亮.孙思邈治痫经验[J].针灸临床杂志,1997;(8):5
[82]符冰,李红.辨证取穴药线埋植治疗癫痫的临床研究[J].甘肃中医,2004;17(9):1
[83]曹忠义,高颂.穴位埋线治疗癫痫60例[J].上海针灸杂志,2000;19(3):47
[84]邓元江,王净净,林亚平等.穴位埋线加小剂量抗痫西药治疗癫痫全身强直一阵挛发作临床观察[J].中国针灸,2001;2l(5):271
[85]崔红,平军辉,曹永贺.穴位埋线联合口服中药治疗癫痫68例[J].中医研究,2006;19(9):61
[86]徐志凤.埋线与中药综合治疗癫痫40例临床观察[J].上海针灸杂志,2006;25(12):13
[87]欧广升.挑刺加埋线治疗癫痫125例临床观察[J].湖南中医学院学报,2000:20(2):63
[88]黄德礼,牛瑞堂.头穴穿刺埋线为主治疗癫痫100例[J].中医外治杂志,1998;7(5):12
[89]聂卉,丁福荣.头穴埋线治疗癫痫50例临床观察[J].中国针灸,1996;77(2):21
[90]李红,张家维.头穴为主埋植药线治疗癫痫112例疗效观察[J].针灸临床杂志,2004,20(6):47
[91]吴绪平,张道敬.穴位埋线治疗癫痫54例[J].中国民间疗法,2000;8(4):18
[92]田海生,王春生,杨丙山.任督脉埋线治疗癫瘸60例[J].中医外治杂志,1997;6(6):42
[93]李福库,王爱英.长强穴埋线治疗癫痫[J].实用中医内科杂志,1996;10(1):48
[94]李希希,张家维,赖新生.穴位埋线法治疗癫痫的临床研究[J].广州中医药大学学报,1997;14(3):167
[95]林军,邓倩萍,张家维.穴位埋线治疗癫痫160例疗效观察.中国针灸,2001;(11):653-654
[96]闫万魁.穴位埋线治疗癫痫100例临床观察[J].中国针灸,1998;6:377
[97]许云祥,张家维,邓倩萍.穴位埋线疗法及其在癫痫治疗中的应用[J].中医药信息,2003;20(1):35
[98]庄礼兴,丁晓虹.穴位埋药线法为主治疗癫痫22例疗效观察[J].新中医,2004;36(1):46
[99]张静,李玉竹,庄礼兴.穴位埋线疗法为主治疗全身强直一阵挛型癫痫90例[J].针灸临床杂志,2006;22(6):8
[100]聂卉,程为平,藤滨权.头穴埋线及中、西药物治疗癫痫的比较研究[J].中国中医药科技,1998;5(1):30
[101]鲁兆麟,王永炎.中医内科学[M].北京:人民卫生出版社,1999:145.
[102]钟建民,毛定安.新提议的国际癫痫诊断体系[J].国外医学·儿科学分册,2003:30(6):330-333
[103]刘金民,江涛.中医癫痫病证诊治标准化的思考[J].中西医结合学报,2006;4(6):572
[104]Miller JW,Ferrendelli JA.Brain Res,1990:508:297
[105]裴印权,王大仁.实验性动物癫痫模型[J].国外医学·神经精神疾病分册,1988;(1):13
[106]邓元江,刘卫英,梁伟雄等.穴位埋线对实验性癫痫大鼠脑电图的影响[J].广州中医药大学学报,2006;23(3):237
[107]Snead OC.Epilepsia,1988;29(2):361
[108]周友龙,白清林.针刺对青霉素致痫大鼠脑电图影响的实验研究[J].河南中医,1998:18(2):29
[109]吴定宗,万平,张志雄等.电针遏制癫痫小发作的实验研究(一)[J].上海针灸杂志,1999;18(6):32
[110]闰丽萍,李建军.针刺对实验性急性癫痫大鼠脑干γ-氨基丁酸和谷氨酸含量的影响[J].中国针灸,1999;(4):235
[111]Diehl GR,Smialowski A,Gotwo T.Epilepsia,1984:259(4):506-509
[112]张瑞华,王玉平.癫痫点燃模型的研究进展[J].脑与神经疾病杂志,2006;14(3):235
[113]周友龙.针刺对癫痫大鼠脑电图影响的实验研究[J].中国中医基础医学杂志,1999:5(6):48
[114]张颖,刘芳.针刺对电刺激致痫动物模型影响的实验研究[J].河南医药信息,1999:7(7):10
[115]杨帆,徐国龙,王频等.电针对癫痫大鼠海马内cAMP、cGMP含量的影响[J].中国中医药科技,2002;9(4):199
[116]高唱,等.电针对侧脑室注入马桑内酯所致大鼠海马单位痫样放电的影响[J].针刺研究,1991;16(1):54
[117]冯正直,等.电针对大鼠侧脑室注入红藻氨酸所致海马痫样丛状放电的影响[J].第三军医大学学报,1993;15(3):216
[118]殷克敬,等.磁极针对癫痫抑制作用及其机理的实验研究[J].中国针灸,1999;19(10):620
[119]朱镜,等.针刺对实验性癫痫大鼠Ach与痫样放电的影响[J].上海针灸杂志,1991;(1):32
[120]朱镜,等.手捻针与电针对实验性癫痫大鼠大脑皮层的动态研究[J].上海针灸杂志,1994;13(6):281
[121]刘卫英,邓元江,彭楚湘等.穴位埋线对实验性癫痫大鼠大脑皮质氨基酸类神经递质的影响[J].中医研究,2005;18(12):6
[122]刘俊,等.大鼠海人藻酸诱发癫病及针刺抗痫时海马内氨基酸释放的变化[J]. 针刺研究,1995;20(3):50
[123]程介士,等.针刺抗癫痫的机理-海马内阿片肽及氨基酸系统与针刺治疗癫痫作用的关系[J].医学研究通讯,1997;26(11):22
[124]高焕民,等.大鼠海马内微量注射强啡肽抗体针刺治疗癫痫的影响[J].医学综述,1998;4(5):253
[125]金渊真,李忠仁,马骋等.电针对癫痫大鼠脑组织及肝脏的一氧化氮和一氧化氮合酶含量的影响[J].中国临床康复,2005;9(9):114
[126]陈文华,丁晓虹,庄礼兴.穴位埋药线对癫痫持续状态后大鼠海马神经元c-jun、bcl-2蛋白表达的影响.广州中医药大学学报,2004;21(2):116
[127]陈文华,庄礼兴,丁晓虹.穴位埋药线对癫痫持续状态大鼠海马神经元凋亡的影响[J].中国临床康复,2006:10(31):96
[128]杨茹,等.实验性癫痫及电针抗痫时大鼠海马内胆囊收缩素基因表达的变化[J].针刺研究,1996;21(2):62
[129]王布尔,等.癫痫发作及电针时脑内c-fos蛋白的表达[J].中国药理学报,1994;15(1)
[130]黄志农,等.电针和7-硝基吲唑对癫痫的效应及其脑内一氧化氮的关系[J].生理学报,1999;51(5):508
[131]张淑琴,林卫红,赵丽曼.实验性癫痫不同脑区细胞凋亡的观察及意义[J].中风与神经疾病杂志,2002;19(4):205
[132]张丽萍,方卓,武丽等.草果知母汤对戊四唑慢性诱导癫痫模型大鼠脑内海马区凋亡调控因子P53蛋白表达的影响[J].中国临床康复,2006;10(31):25
[133]全国第一届癫痫学术会议.癫痫发作分类法(草案).中华神经精神科杂志,1986;19:256
[134]国家中医药管理局全国脑病急症协作组.痫证诊断与疗效评定标准.北京中医学院学报,1993;16(4):13.
[135]Hornung J,et al.Com Neurol,1989:183:425
[136]Pollard H,et al.Neuroscience,1994:63:7
[137]Sakhi S,et al.Proc.Natl Acad.Sci.USA,1994:91:7525
[138]Racine RJ.Kindling:The first decade[J].Neurosurgery,1978:3:334
[139]陈旭东,赵文清,吴耀晨,等.神经系统中的凋亡.中国老年学杂志,1999;7(19):248
[140]李震中,张苏明,白欣立,等.神经元的生存与凋亡.脑与神经疾病杂志,1996;3:19
[141]Babb TL.Adv Exp Med Biol,1986;203:115-125
[142]Sloviter RS.Science,1987:235:73-76
[143]Sloviter RS.Hippocampus,1991:1:41-46
[144]Pretel S,Applegate CD,Piekut D.Acta Histochem,1997:99:71
[145]Pollard H,Charriaut-Marlangue C,Cantagrel S,et al.Neuroscience,1994:63:7-18
[146]Nitecka L,Tremblay E,Charton G,et al.Neuroscience,1984:13:1073-1094
[147]Olney JW,Rhee V,Ho DL.Brain Res,1974:77:507-512
[148]何伟刚,曹雪涛.P53转录非依赖活性诱导细胞凋亡的研究进展[J].中国肿瘤生物治疗杂志,2005;12(3):229.
[149]Yuan XM,Li W,Dalen H,et al.Lysosomal destabilization inP53-induced apoptosis[J].Proc Nail Acad Sci USA,2002:99(9):6286-6291.
[150]Sakhi S,Bruce A,Sun N,et al.P53 induction is associated with neuronal damage in the central nervous system[J],Proc Natl Acad Sci USA,1994:91(16):7525-7529.
[151]Sakhi S,Sun N,Wing LL,et al.Neuclear accumulation of P53 protein following kainic acid-induced seizures[J],Neuroreport,1996:7(2):493-496.
[152]程桂玲,迟兆富.P53及其下游靶基因与癫痫[J].河南实用神经疾病杂志,2002;5(1):88-89.
[153]Gillardon F,Wickert H,Zimmermann M,et al.Up-regulation of bax and down-regulation of bcl-2 is associated with kainite-induced apoptosis in mouse brain[J],Neurosci Lett,1995:192(2):85-88.
[154]Monney L.Biochem Biophys Res Commun,1996:221:340
[155]Hockenbery DM,et al.Cell,1993:75:241
[156]Garcia I,et al.Science,1992:258:302
[157]Krajeuski S,et al.Cancer Research,1993:53:4701
[158]Jurgensmeier JM,Xie ZH,Deveraux Q,et al.Proc Nail Acad USA,1998:95:4997
[159]李震中,阮旭中,王群,等.bcl-2蛋白在癫痫过程中海马细胞内的变化[J]。脑与神经疾病杂志.1996;4(2):71-73
[160]李震中,阮旭中,白欣立,等.bcl-2、bcl-xl和bax mRNA在癫痫后DNA损伤诱导海马细胞凋亡中的作用[J].脑与神经疾病杂志,1997:5(3):141-143
[161]Zhang LX,et al.Mol Brain Res,1998:55:198
[162]Yachnis AT,et al.J.Neuropathol Exp Neurol,1997:56:186
[163]van de Bovenkamp-Janssen MC,Akhmadeev A,Kalimullina L,et al.Synaptology of the rostral reticular thalamic nucleus of absentce epileptic WAG/Rij rats[J].Neurosci Res.2004:48(1):21-31
[164]姚小卫.海马与杏仁核电点燃建立复杂部分性癫痫模型的对照研究[J].中华现代医学与临床,2006;4(4):76-78
[165]Post RM.Neurobilolgy of seizures and behaveioral abnormallyties[J].Epilepsia.2004:45(Suppl 2):5-14
[166]戴启麟.抗癫痫药物增加癫痫发作及对策[J].实用医学杂志,2001;17(12):1138-1139
[2]史玉泉.神经病学新理论与新技术[M].上海:上海科技教育出版社,1998:12
[3]罗云坚,刘茂才.神经科专病中医临床诊治[M].北京:人民卫生出版社,2000:10
[4]瞿治平,俞丽云.实用癫痫学[M].上海:上海医科大学出版社,1997
[5]孔峰.癫痫发作时的脑电图分析[J].河南医学研究,1997;6(2):142-144
[6]宋永建等.24小时动态脑电图对癫痫的诊断意义[J].临床脑电学杂志.1998;7(2):80一82
[7]许虹等.癫痫患者的脑电图与CT对比研究[J].临床脑电学杂志,1998;7(1):9-11
[8]陈淑兰等.不同年龄癫痫患者临床与头颅MRI改变的研究[J].中风与神经疾病杂志,1998:15(4):231-232
[9]马志海等.小儿癫痫SPECT脑血流显像与CT、MRI、EEG的对比分析[J].西北国防医学杂志,1997;18(1):10-11
[10]赵延祜.30例儿童癫痫脑血流灌注显像检查的临床意义[J].临床儿科杂志,1998:16(2):97
[11]赵传胜,高旭光.抗癫痫新药Topiramate[J].国外医学,神经病学神经外科学分册,1998;25(1):27-30
[12]Privitera M,et al.Neurology[M],1996:46:1678
[13]Meldrum BS,et al.3rd European Congress of Epileptology,1998 May Warsaw
[14]冯亚波,姚红.抗痫药物的致痫作用[J].国外医学,神经病学神经外科学分册。1999;26(4):169-171
[15]Baker GA,Smith DF,Dewey M,ET AL.The initial development of a health-related quality of life model as an outcome measure in epilepsy[J].Epilepsy Res,1993;16:65-81
[16]欧阳华,刘弋戈.抗癫痫药物不良反应分析[J].儿科药学杂志,2005;11(4):57-59
[17]张军强,赵红宁,王晓明.癫痫的非药物治疗研究现状[J].川北医学院学报,2007:22(4):383-386
[18]谭启富.立体定向放射外科与癫痫[J].功能性和立体定向神经外科杂志,1997;10(1):45-46
[19]Houseton TX.Physician's manual for the VNS therapy pulsemodd 102Generator[J].Cyberonics Inc,2002:9-15
[20]郑乃智.癫痫的基因治疗[J].医学研究通讯.1996;25(3):1-2
[21]Bergner M.Quality of life,health status,and clinical research[J].Med Care,1989,127(Supp1):S148-S156
[22]Laine C,Davidoff F.Patient-centered medicine.A professional evolution[J].JAMA,1996,275(2):152-156
[23]CramerJA,Perrine K,Devinsky O.et al.Development and cross-cultural translations of a 31-item quality of life in epilepsy inventory[J].Epilepsia,1998,39(1):81-88
[24]Heroder M,Oun A,Haldre S,et al.Epilepsy in Estonia:a quality-of-life study[J].Epilepsia,2001,42(8):1061-1073
[25]Lam J,Rozsavolgyi M,Soos G,et al.Quality of life of patients with epilepsy(Hungarian survey)[J].Seizure,2001,lO(2):lO0-106
[26]Tortes X,Arroyo S,Araya S,et al.The Spanish Version of the Quality-of-Life in Epilepsy Inventory(QOLIE-31):translation,validity,and reliability[J].Epilepsia,1999,40(9):1299-1304
[27]Renfroe JB,Wheless JW.Earlier use of adjunctive vagus nerve stimulation therapy for refractory epilepsy[J].Neurology,2002,59(6 Suppl 4):S26-30
[28]Wiebe S,Matijevic S,Eliasziw M,et al.Clinically important change in quality of life in epilepsy[J].J Neurol Neurosurg Psychiatry,2002,73(2):116-120
[29]Birbeck GL,Hays RD,Cui x,et al.Seizure reduction and quality of life improvements in people with epilepsy[J].Epilepsia,2002,43(5):535-538
[30]Andelman F,Fried Ⅰ,NeufeldMY.Quality of life self-assessment as a function of lateralization of lesion in candidates for epilepsy surgery[J].Epilepsia,2001,42(4):549-555
[31]Kline LN,Rentz AM,Grace EM.Evaluating health-related quality of life outcomes in clinical trials of antiepileptic drug therapy[J].Epilepsia,1998,39(9):965-977
[32]任晓琳,梁平,刘雪琴.癫痫患者生活质量量表-31(中文版)的翻译及修订[J].解放军护理杂志,2003,20(4):99-101
[33]Colling JA,Perrine K,Life fulfillment in an epilepsy sample from The United States[J].Soc Sci Med,1995,40;1579-1584
[34]Cramer JA.Quality Of life assessment in clinicl pratice[J].Neurology.1999,53(2):S49-S52
[35]朱丹彤,肖波,谢光洁,等.成年癫痫病的的生活质量及其影响因素[J].中华神经科杂志,2002,35(3):139-141
[36]解新荣,徐江涛,王毅,等.特发性癫痫患者的生活质量[J].中国行为医学科学,2001,10(5):427-428
[37]赵萍,郭秀东,严文康.癫痫儿童的心理障碍及其干预[J].中国儿童保健杂志.2002,10(2):76-78
[38]华蓓苓,周长发,朱兴海.中医病证专辑·癫狂痫[M].北京:中医古籍出版社,1990 第二版:12
[39]许沛虎.中医脑病学[M].北京:中国医药科技出版社,1998;8:485-499
[40]孙怡,杨任民.实用中西医结合神经病学[M].北京:人民卫生出版社,1999:447-466
[41]张登本.中医神经精神病学[M].北京:中国医药科技出版社,2000:306-317
[42]黄斌.癫痫中西医论治[M].北京:人民卫生出版社,1999:23-88
[43]刘立公,顾杰.癫痫证的古代针灸特点探讨[J].针灸临床杂志,2000;16(1):1-2
[44]奚永江,等.《针灸大成》中俞穴功效的计算机分析[J].上海针灸杂志,1988;(2):36
[45]刘立公,等。八纲病证的取穴特点初探[J].上海中医药杂志,1993;(5):42
[46]徐笨人,葛书翰。针刺大椎穴治疗癫痫95例[J].中国针灸,1982;(2):4-5
[47]徐非.督脉穴埋线治疗癫痫60例临床观察[J].国医论坛,1999;74(2):34
[48]刘永久.“神四针”“顶三针”治疗癫痫25例[J].辽宁中医杂志,1994;21(3):137
[49]刘胜利.针刺治疗癫痫病22例体会[J].针灸临床杂志,1997;13(8):44
[50]彭光超.针灸治疗癫痫54例的疗效观察[J].江西中医药,1990;21(3):40
[51]谷世喆,夏勇,张洪林.针灸治疗癫痫27例[J].北京中医药大学学报,1998;(4):66
[52]王进才.“背三针”治疗癫痫500例临床观察[J]。河南中医,1997;17(1):37
[53]杨子雨.针刺大椎、腰奇穴治疗癫痫108例[J].针灸临床杂志,1996:12(7、8):84-85
[54]程好收.针灸配合中药治疗癫痫100例观察[J].中级医刊,1989;21(12):51
[55]孟兰成.针刺华佗夹脊治疗癫痫的临床观察[J].中医药研究,1994;(3):47
[56]张丹玲.治脑三穴诊治癫痫病62例体会[J].中医函授通讯,1991;(2):41
[57]刘德荣.针刺为主治疗原发性癫痫932例疗效观察[J].针灸临床杂志,1993;9(6):17-18
[58]戴海玉,卫海英,沈丽.挑针治疗癫痫32例临床观察[J].河北中医,2000;22(9):661-661
[59]孙仁平,吴峰,邱凤翱,等。小针刀拔罐加埋线治疗癫痫病i000例体会[J].中国针灸,1999;19(9):547-548
[60]况琼,邹德霖,喻晓梨,等。针药治疗癫痫40例临床观察[J].江西中医药,1996;27(6):74-74
[61]孙曙霞.针刺配合药物贴脐治疗癫痫48例[J].上海针灸杂志,1997;16(1):13
[62]王海亮.孙思邈治痫方法初探[J].针灸临床杂志,1997;13(8):57
[63]李桂初.灸家兔癫痫模型百会及会阴穴的实验观察[J].湖南中医杂志,1994;10(7):51
[64]张鲁豫.穴位穿线配合艾灸治疗癫痫13例[J].新中医,1995;27(1):34-35
[65]旷秋和.时令灯火灸治疗癫痫50例疗效观察[J].针灸临床杂志,2003;19(7):54-54
[66]李效芳,马志刚.头皮针治疗癫痫40例[J].中国针灸,2000;20(8):475-475
[67]史子玉.头针治疗癫痫98例疗效观察[J].中国针灸,1986;6(1):17
[68]许永迅.长针和头针为主治疗运动性癫痫[J].上海针灸杂志,1991;(3):16-17
[69]曹晓来.头针配合电针治疗癫痫的临床观察[J].安徽中医临床杂志,1996;8(1):45
[70]郑祖艳.头穴电针治疗癫痫42例疗效观察[J].中医药信息,2000;17(1):53
[71]张锦华.针灸加电治疗痫症22例[J].中国针灸,2003;23(9):517
[72]潘静,赵瑞芹,马建宏,等.耳穴治疗小儿癫痫疗效观察[J].河北医药,2004;26(4):322-322
[73]郭双健等.耳针治疗癫痫临床观察[J].针灸学报,1992;8(6):16
[74]郑作祯.三棱针刺长强穴治疗癫痫136例[J].浙江中医杂志,1995;30..(7):310
[75]高永波.火针与毫针结合治疗癫痫76例[J].针灸临床杂志,1997;13(12):24-25
[76]许永迅.长针和头针为主治疗运动性癫痫[J].上海针灸杂志,1991;10(3):16
[77]郭勤英,杜秋来,白锡三,等.点穴治疗癫痫小发作17例[J].浙江中医杂志,1993:28(12):545
[78]刘安然.灸大椎穴治验5则[J].安徽中医临床杂志,1998;(3):169
[79]李希希,张家维,赖新生.穴位埋线法治疗癫痫的临床研究[J].广州中医药大学学报,1997:14(3):167-i68
[80]王兆荣.吴茱萸贴敷穴位治疗癫痫病[J].江西中医药,1997;(2):61
[81]王海亮.孙思邈治痫经验[J].针灸临床杂志,1997;(8):5
[82]符冰,李红.辨证取穴药线埋植治疗癫痫的临床研究[J].甘肃中医,2004;17(9):1
[83]曹忠义,高颂.穴位埋线治疗癫痫60例[J].上海针灸杂志,2000;19(3):47
[84]邓元江,王净净,林亚平等.穴位埋线加小剂量抗痫西药治疗癫痫全身强直一阵挛发作临床观察[J].中国针灸,2001;2l(5):271
[85]崔红,平军辉,曹永贺.穴位埋线联合口服中药治疗癫痫68例[J].中医研究,2006;19(9):61
[86]徐志凤.埋线与中药综合治疗癫痫40例临床观察[J].上海针灸杂志,2006;25(12):13
[87]欧广升.挑刺加埋线治疗癫痫125例临床观察[J].湖南中医学院学报,2000:20(2):63
[88]黄德礼,牛瑞堂.头穴穿刺埋线为主治疗癫痫100例[J].中医外治杂志,1998;7(5):12
[89]聂卉,丁福荣.头穴埋线治疗癫痫50例临床观察[J].中国针灸,1996;77(2):21
[90]李红,张家维.头穴为主埋植药线治疗癫痫112例疗效观察[J].针灸临床杂志,2004,20(6):47
[91]吴绪平,张道敬.穴位埋线治疗癫痫54例[J].中国民间疗法,2000;8(4):18
[92]田海生,王春生,杨丙山.任督脉埋线治疗癫瘸60例[J].中医外治杂志,1997;6(6):42
[93]李福库,王爱英.长强穴埋线治疗癫痫[J].实用中医内科杂志,1996;10(1):48
[94]李希希,张家维,赖新生.穴位埋线法治疗癫痫的临床研究[J].广州中医药大学学报,1997;14(3):167
[95]林军,邓倩萍,张家维.穴位埋线治疗癫痫160例疗效观察.中国针灸,2001;(11):653-654
[96]闫万魁.穴位埋线治疗癫痫100例临床观察[J].中国针灸,1998;6:377
[97]许云祥,张家维,邓倩萍.穴位埋线疗法及其在癫痫治疗中的应用[J].中医药信息,2003;20(1):35
[98]庄礼兴,丁晓虹.穴位埋药线法为主治疗癫痫22例疗效观察[J].新中医,2004;36(1):46
[99]张静,李玉竹,庄礼兴.穴位埋线疗法为主治疗全身强直一阵挛型癫痫90例[J].针灸临床杂志,2006;22(6):8
[100]聂卉,程为平,藤滨权.头穴埋线及中、西药物治疗癫痫的比较研究[J].中国中医药科技,1998;5(1):30
[101]鲁兆麟,王永炎.中医内科学[M].北京:人民卫生出版社,1999:145.
[102]钟建民,毛定安.新提议的国际癫痫诊断体系[J].国外医学·儿科学分册,2003:30(6):330-333
[103]刘金民,江涛.中医癫痫病证诊治标准化的思考[J].中西医结合学报,2006;4(6):572
[104]Miller JW,Ferrendelli JA.Brain Res,1990:508:297
[105]裴印权,王大仁.实验性动物癫痫模型[J].国外医学·神经精神疾病分册,1988;(1):13
[106]邓元江,刘卫英,梁伟雄等.穴位埋线对实验性癫痫大鼠脑电图的影响[J].广州中医药大学学报,2006;23(3):237
[107]Snead OC.Epilepsia,1988;29(2):361
[108]周友龙,白清林.针刺对青霉素致痫大鼠脑电图影响的实验研究[J].河南中医,1998:18(2):29
[109]吴定宗,万平,张志雄等.电针遏制癫痫小发作的实验研究(一)[J].上海针灸杂志,1999;18(6):32
[110]闰丽萍,李建军.针刺对实验性急性癫痫大鼠脑干γ-氨基丁酸和谷氨酸含量的影响[J].中国针灸,1999;(4):235
[111]Diehl GR,Smialowski A,Gotwo T.Epilepsia,1984:259(4):506-509
[112]张瑞华,王玉平.癫痫点燃模型的研究进展[J].脑与神经疾病杂志,2006;14(3):235
[113]周友龙.针刺对癫痫大鼠脑电图影响的实验研究[J].中国中医基础医学杂志,1999:5(6):48
[114]张颖,刘芳.针刺对电刺激致痫动物模型影响的实验研究[J].河南医药信息,1999:7(7):10
[115]杨帆,徐国龙,王频等.电针对癫痫大鼠海马内cAMP、cGMP含量的影响[J].中国中医药科技,2002;9(4):199
[116]高唱,等.电针对侧脑室注入马桑内酯所致大鼠海马单位痫样放电的影响[J].针刺研究,1991;16(1):54
[117]冯正直,等.电针对大鼠侧脑室注入红藻氨酸所致海马痫样丛状放电的影响[J].第三军医大学学报,1993;15(3):216
[118]殷克敬,等.磁极针对癫痫抑制作用及其机理的实验研究[J].中国针灸,1999;19(10):620
[119]朱镜,等.针刺对实验性癫痫大鼠Ach与痫样放电的影响[J].上海针灸杂志,1991;(1):32
[120]朱镜,等.手捻针与电针对实验性癫痫大鼠大脑皮层的动态研究[J].上海针灸杂志,1994;13(6):281
[121]刘卫英,邓元江,彭楚湘等.穴位埋线对实验性癫痫大鼠大脑皮质氨基酸类神经递质的影响[J].中医研究,2005;18(12):6
[122]刘俊,等.大鼠海人藻酸诱发癫病及针刺抗痫时海马内氨基酸释放的变化[J]. 针刺研究,1995;20(3):50
[123]程介士,等.针刺抗癫痫的机理-海马内阿片肽及氨基酸系统与针刺治疗癫痫作用的关系[J].医学研究通讯,1997;26(11):22
[124]高焕民,等.大鼠海马内微量注射强啡肽抗体针刺治疗癫痫的影响[J].医学综述,1998;4(5):253
[125]金渊真,李忠仁,马骋等.电针对癫痫大鼠脑组织及肝脏的一氧化氮和一氧化氮合酶含量的影响[J].中国临床康复,2005;9(9):114
[126]陈文华,丁晓虹,庄礼兴.穴位埋药线对癫痫持续状态后大鼠海马神经元c-jun、bcl-2蛋白表达的影响.广州中医药大学学报,2004;21(2):116
[127]陈文华,庄礼兴,丁晓虹.穴位埋药线对癫痫持续状态大鼠海马神经元凋亡的影响[J].中国临床康复,2006:10(31):96
[128]杨茹,等.实验性癫痫及电针抗痫时大鼠海马内胆囊收缩素基因表达的变化[J].针刺研究,1996;21(2):62
[129]王布尔,等.癫痫发作及电针时脑内c-fos蛋白的表达[J].中国药理学报,1994;15(1)
[130]黄志农,等.电针和7-硝基吲唑对癫痫的效应及其脑内一氧化氮的关系[J].生理学报,1999;51(5):508
[131]张淑琴,林卫红,赵丽曼.实验性癫痫不同脑区细胞凋亡的观察及意义[J].中风与神经疾病杂志,2002;19(4):205
[132]张丽萍,方卓,武丽等.草果知母汤对戊四唑慢性诱导癫痫模型大鼠脑内海马区凋亡调控因子P53蛋白表达的影响[J].中国临床康复,2006;10(31):25
[133]全国第一届癫痫学术会议.癫痫发作分类法(草案).中华神经精神科杂志,1986;19:256
[134]国家中医药管理局全国脑病急症协作组.痫证诊断与疗效评定标准.北京中医学院学报,1993;16(4):13.
[135]Hornung J,et al.Com Neurol,1989:183:425
[136]Pollard H,et al.Neuroscience,1994:63:7
[137]Sakhi S,et al.Proc.Natl Acad.Sci.USA,1994:91:7525
[138]Racine RJ.Kindling:The first decade[J].Neurosurgery,1978:3:334
[139]陈旭东,赵文清,吴耀晨,等.神经系统中的凋亡.中国老年学杂志,1999;7(19):248
[140]李震中,张苏明,白欣立,等.神经元的生存与凋亡.脑与神经疾病杂志,1996;3:19
[141]Babb TL.Adv Exp Med Biol,1986;203:115-125
[142]Sloviter RS.Science,1987:235:73-76
[143]Sloviter RS.Hippocampus,1991:1:41-46
[144]Pretel S,Applegate CD,Piekut D.Acta Histochem,1997:99:71
[145]Pollard H,Charriaut-Marlangue C,Cantagrel S,et al.Neuroscience,1994:63:7-18
[146]Nitecka L,Tremblay E,Charton G,et al.Neuroscience,1984:13:1073-1094
[147]Olney JW,Rhee V,Ho DL.Brain Res,1974:77:507-512
[148]何伟刚,曹雪涛.P53转录非依赖活性诱导细胞凋亡的研究进展[J].中国肿瘤生物治疗杂志,2005;12(3):229.
[149]Yuan XM,Li W,Dalen H,et al.Lysosomal destabilization inP53-induced apoptosis[J].Proc Nail Acad Sci USA,2002:99(9):6286-6291.
[150]Sakhi S,Bruce A,Sun N,et al.P53 induction is associated with neuronal damage in the central nervous system[J],Proc Natl Acad Sci USA,1994:91(16):7525-7529.
[151]Sakhi S,Sun N,Wing LL,et al.Neuclear accumulation of P53 protein following kainic acid-induced seizures[J],Neuroreport,1996:7(2):493-496.
[152]程桂玲,迟兆富.P53及其下游靶基因与癫痫[J].河南实用神经疾病杂志,2002;5(1):88-89.
[153]Gillardon F,Wickert H,Zimmermann M,et al.Up-regulation of bax and down-regulation of bcl-2 is associated with kainite-induced apoptosis in mouse brain[J],Neurosci Lett,1995:192(2):85-88.
[154]Monney L.Biochem Biophys Res Commun,1996:221:340
[155]Hockenbery DM,et al.Cell,1993:75:241
[156]Garcia I,et al.Science,1992:258:302
[157]Krajeuski S,et al.Cancer Research,1993:53:4701
[158]Jurgensmeier JM,Xie ZH,Deveraux Q,et al.Proc Nail Acad USA,1998:95:4997
[159]李震中,阮旭中,王群,等.bcl-2蛋白在癫痫过程中海马细胞内的变化[J]。脑与神经疾病杂志.1996;4(2):71-73
[160]李震中,阮旭中,白欣立,等.bcl-2、bcl-xl和bax mRNA在癫痫后DNA损伤诱导海马细胞凋亡中的作用[J].脑与神经疾病杂志,1997:5(3):141-143
[161]Zhang LX,et al.Mol Brain Res,1998:55:198
[162]Yachnis AT,et al.J.Neuropathol Exp Neurol,1997:56:186
[163]van de Bovenkamp-Janssen MC,Akhmadeev A,Kalimullina L,et al.Synaptology of the rostral reticular thalamic nucleus of absentce epileptic WAG/Rij rats[J].Neurosci Res.2004:48(1):21-31
[164]姚小卫.海马与杏仁核电点燃建立复杂部分性癫痫模型的对照研究[J].中华现代医学与临床,2006;4(4):76-78
[165]Post RM.Neurobilolgy of seizures and behaveioral abnormallyties[J].Epilepsia.2004:45(Suppl 2):5-14
[166]戴启麟.抗癫痫药物增加癫痫发作及对策[J].实用医学杂志,2001;17(12):1138-1139