小儿多发性抽动症处方规律分析及复方中药对TS模型鼠行为的影响
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摘要
目的:探讨小儿多发性抽动症临床特征及中医证型分布规律,总结导师王素梅教授运用中药治疗小儿多发性抽动症的处方规律,为临床运用六君子汤合泻青丸加味提供临床基础。对亚氨基二丙腈诱导的多发性抽动症小鼠模型进行行为学评价,并观察六君子汤合泻青丸加味对此模型行为学改变的影响,从而为临床提供实验依据。
方法:采用自拟“多发性抽动症观察表”,对家长及患儿进行问卷调查,核实病史,询问包括以脏腑辨证为主的中医证候诊断所需的所有症状。腹腔注射亚氨基二丙腈建立多发性抽动症小鼠模型,分别给予多发性抽动症小鼠复方中药六君子汤合泻青丸加味与泰必利进行灌胃治疗,经自主活动仪计数、点头次数及爬杆时间对比观察用药前后小鼠行为学的改变。
结果:
1.小儿多发性抽动症与性别的关系
415例多发性抽动症患儿中,男322例,女93例,男女比例3.46:1,符合既往文献资料报道。
2.小儿多发性抽动症与年龄的关系
2.1发病年龄
根据纳入标准收录统计的415例多发性抽动症患儿中,最小发病年龄2岁,最大发病年龄为16岁,平均发病年龄(7.06±2.53)岁,2～3~-岁2例(0.48%),3～7~-岁188例(45.30%),7～13~-岁215例(51.81%),13～16~-岁10例(2.41%)。其中以学龄期7～13~-岁发病率最高。
2.2就诊年龄
本组患儿的就诊年龄分布情况是4～7~-岁79例(19.04%),7～13~-岁263例(63.37%),13～18~-岁73例(17.59%),平均年龄(9.56±3.14)岁。
3.小儿多发性抽动症与病程的关系
入组患儿中,病程最长者为12年,最短不到1年,平均病程为(2.51±2.37)年。由此可见多发性抽动症病程持续时间较长,已逐渐引起了人们的关注。
4.小儿多发性抽动症与中医证型分布规律
本次调查中显示:多发性抽动症中医证型以脾虚肝亢为主,出现频率数为172,构成比为41.45%;其次为脾虚痰聚,出现频率数为125,构成比为30.12%;气郁化火出现频率为109,构成比为26.27%;阴虚风动出现频率最少,为9,构成比为2.17%。并分别对多发性抽动症患儿的性别、就诊年龄与中医证型的关系进行统计学分析,P＞0.05,提示男女的中医证型构成情况、不同年龄段的中医证型构成情况没有统计学差异,即以男女分类或以不同年龄段分类,四种中医证型的构成比排序均相同,依次为:脾虚肝亢、脾虚痰聚、气郁化火、阴虚风动。
5.小儿多发性抽动症治疗中药使用规律
对纳入观察的640份病例处方进行分析,共涉及药物153种,其中出现频数在100次以上的有31种,使用频率在前十位的依次为防风469次、地龙418次、木瓜381次、伸筋草378次、谷精草318次、菊花305次、荆芥303次、葛根298次、柴胡295次、钩藤283次,其次是石菖蒲283次、半夏275次、陈皮273次、胆星266次、白芍257次、广郁金250次、知母246次、夏枯草213次、山药212次、茯苓200次、炒白术181次、党参160次等。六君子汤合泻青丸中的各药物在治疗多发性抽动症的药物使用频数中均出现频繁,主要药物的使用频率均在150次以上。
6.亚氨基二丙腈(IDPN)诱导多发性抽动症小鼠模型的行为学评价
经自主活动仪计数、点头次数及爬杆时间测定,发现腹腔注射亚氨基二丙腈诱导多发性抽动症小鼠模型不仅在表现效度上较好地模拟了人类多发性抽动症的临床表现(主要为头和颈部的动作过多),而且具有操作方法较简便,复制成功率高,症状维持时间长等优点,为进一步研究多发性抽动症提供了模型基础。
7.复方中药对TS模型鼠行为学改变的影响
以IDPN诱导的头部抽动动物模型为基础,通过自主活动仪计数、点头次数及爬杆时间测定,比较了复方中药六君子汤合泻青丸与泰必利对小鼠行为的改变。用药后小鼠的自主活动较模型组均降低,且从长期疗效来看,复方中药抑制抽动的效果更优于泰必利。
结论:
1.多发性抽动症以学龄期7～13~-岁发病率最高。
2.男孩的发病率较女孩高。
3.在中医证型分布中,以脾虚肝亢最为多见。其次为脾虚痰聚、气郁化火及阴虚风动。故临床以扶土抑木法为指导,运用六君子汤合泻青丸加味健脾平肝以治疗小儿多发性抽搐症具有理论依据和临床基础。
4.导师王素梅教授治疗多发性抽动症患儿的640份病例处方中,共涉及药物153种,其中出现频数在100次以上的有31种,使用频率在前十位的依次为防风469次、地龙418次、木瓜381次、伸筋草378次、谷精草318次、菊花305次、荆芥303次、葛根298次、柴胡295次、钩藤283次,其次是石菖蒲283次、半夏275次、陈皮273次、胆星266次、白芍257次、广郁金250次、知母246次、夏枯草213次、山药212次、茯苓200次、炒白术181次、党参160次等。六君子汤合泻青丸中的各药物在治疗多发性抽动症的药物使用频数中均出现频繁,主要药物的使用频率均在150次以上。
5.亚氨基二丙腈诱导多发性抽动症小鼠模型较好地模拟了人类多发性抽动症的部分症状,是比较理想的多发性抽动症动物模型。
6.复方中药六君子汤合泻青丸可有效地抑制IDPN诱导的小鼠抽动,且从长期疗效来看,其作用更优于泰必利。
Objective
Discussed clinical characteristics and TCM-based distribution of children with Tourette syndrome,summarized rules of prescriptions which were used by Professor Wang Sumei,in order to provide the clinical foundation for Liujunzi Tang and Xiexing Wan.Evaluated the behavior of iminodipropionitrile (IDPN)-induced mouse model of Tourette syndrome and observed the impact of changes in behavior by herbal medicine,so as to provide experimental basis for clinic.
Methods
Investigated parents and children with TS using self-made "Tourette syndrome survey",including all the symptoms which were needed for TCM diagnosis.Set up TS animal model by intraperitoneal injection of IDPN and treated with Chinese medicine or Tiapridal.Tourette syndrome mice were evaluated by autonomic activities,head nutation and climbing time,and observated behavioral changes each.
Results
1.Tourette syndrome and gender
There were 322 boys and 93 girls in 415 cases of children with Tourette syndrome.Boys outnumbered girls in the ratio of 3.46 to 1,and this was consistent with previous literature reports.
2.Tourette syndrome and age
2.1 Age of onset
In 415 cases of children with Tourette syndrome which were collected according to the standard,the minimum onset age was 2 years old.The maximum was 16 and average age was(7.06±2.53).2 cases were in 2～3~- year-old period (0.48%).188 cases were 3～7~- year-old(45.30%).7～13~- year-old children were 215 cases(51.81%).13～16~- were 10 cases(2.41%).The highest incidence was onset when one was school age from 7 to 13.
2.2 Age of visiting
In this group,the visiting age distribution is 4～7~- year-old of 79 cases (19.04%),7～13~- year-old of 263 cases(63.37%),13～18~- year-old of 73 cases (17.59%),and the average age is(9.56±3.14) years old.
3.Tourette syndrome and course
The longest duration of children in the group was 12 years and the shortest less than one year.The average duration was(2.51±2.37) years.It can be seen that Tourette Syndrome lasted for long period and gradually attracted people' s attention.
4.Tourette syndrome and TCM syndrome distribution
The survey showed that splenic asthenia and liver domination was the most frequent TCM syndrome for Tourette syndrome.The mainly frequency was 172,which constitute more than 41.45%.It followed by spleen asthenia and poly-sputum, frequency of occurrence for 125,which constitute more than 30.12%.Next syndrome was stagnated QI transforming into fire,which happened in 109 cases and constituted more than 26.27%.Stirring of wind due to deficiency of YIN was the least,which only occurred on 9 chileren and constituted 2.17%.The investigator analyzed the relationship between gender and TCM syndrome,visiting age and TCM syndrome,found that boys and girls,different ages all had the same order in TCM syndrome.
5.Rules of Chinese medicine for Tourette syndrome
In the observation of more than 640 prescriptions,there were a total of 153 kinds of Chinese herbs and 31 kinds occurred more than 100 times.The most use of frequency were Fangfeng,used 469 times,and followed by Dilong,418 times, Mugua,381times,Shenjincao,378 times,Gujingcao,318 times,Juhua,305 times, Jingjie,303 times,Gegen,298 times,Chaihu,295 times,Gouteng,283times and so on.The herbs in Liujunzi Tang and Xieqing Wan occurred frequently,and main were all used more than 150 times.
6.Behavior evaluation of the mouse model of Tourette syndrome
Set up TS animal model by intraperitoneal injection of IDPN and evaluated by autonomic activities,head nutation and climbing time.The model had good quality in the performance of validity,easy operation,high rate for copy and maintenance of the symptoms for a long time.This method provided a model foundation for further research of Tourette syndrome.
7.Behavior changes of the TS model mice with compound Chinese medicine
Using the IDPN-induced animal model,compared changes of behavior caused by the Chinese medicine and Tiapridal.The Chinese medicine team and the Tiapridal team both have less action than the model.From a long time,Chinese medicine has better effect than Tiapridal.
Conclusion
1.Tourette syndrome has the highest incidence in school-age 7 to 13~- years old.
2.Incidence in boys is higher than girls.
3.Splenic asthenia and liver domination was the most frequent TCM syndrome for rourette syndrome.It followed by spleen asthenia and poly-sputum,stagnated QI transforming into fire and stirring of wind due to deficiency of YIN.According to invigorating the spleen and purging the green,we use Liujunzi Tang and Xieqing Wan for the treatment of multiple tic disorder in children.
4.In the observation of more than 640 prescriptions,there were a total of 153 kinds of Chinese herbs and 31 kinds occurred more than 100 times.The most use of frequency were Fangfeng,used 469 times,and followed by Dilong,418 times, Mugua,381 times,Shenjincao,378 times,Gujingcao,318 times,Juhua,305 times, Jingjie,303 times,Gegen,298 times,Chaihu,295 times,Gouteng,283 times and so on.The herbs in Liujunzi Tang and Xieqing Wan occurred frequently,and main were all used more than 150 times.
5.IDPN-induced Tourette syndrome mouse model simulates parts of the human Tourette's syndrome symptoms,and is a good animal model of Tourette syndrome.
6.Liujunzi Tang and Xieqing Wan has a good effect on the tics of the IDPN-induced animal model.From a long time,Chinese medicine is better than Tiapridal.
方法:采用自拟“多发性抽动症观察表”,对家长及患儿进行问卷调查,核实病史,询问包括以脏腑辨证为主的中医证候诊断所需的所有症状。腹腔注射亚氨基二丙腈建立多发性抽动症小鼠模型,分别给予多发性抽动症小鼠复方中药六君子汤合泻青丸加味与泰必利进行灌胃治疗,经自主活动仪计数、点头次数及爬杆时间对比观察用药前后小鼠行为学的改变。
结果:
1.小儿多发性抽动症与性别的关系
415例多发性抽动症患儿中,男322例,女93例,男女比例3.46:1,符合既往文献资料报道。
2.小儿多发性抽动症与年龄的关系
2.1发病年龄
根据纳入标准收录统计的415例多发性抽动症患儿中,最小发病年龄2岁,最大发病年龄为16岁,平均发病年龄(7.06±2.53)岁,2～3~-岁2例(0.48%),3～7~-岁188例(45.30%),7～13~-岁215例(51.81%),13～16~-岁10例(2.41%)。其中以学龄期7～13~-岁发病率最高。
2.2就诊年龄
本组患儿的就诊年龄分布情况是4～7~-岁79例(19.04%),7～13~-岁263例(63.37%),13～18~-岁73例(17.59%),平均年龄(9.56±3.14)岁。
3.小儿多发性抽动症与病程的关系
入组患儿中,病程最长者为12年,最短不到1年,平均病程为(2.51±2.37)年。由此可见多发性抽动症病程持续时间较长,已逐渐引起了人们的关注。
4.小儿多发性抽动症与中医证型分布规律
本次调查中显示:多发性抽动症中医证型以脾虚肝亢为主,出现频率数为172,构成比为41.45%;其次为脾虚痰聚,出现频率数为125,构成比为30.12%;气郁化火出现频率为109,构成比为26.27%;阴虚风动出现频率最少,为9,构成比为2.17%。并分别对多发性抽动症患儿的性别、就诊年龄与中医证型的关系进行统计学分析,P＞0.05,提示男女的中医证型构成情况、不同年龄段的中医证型构成情况没有统计学差异,即以男女分类或以不同年龄段分类,四种中医证型的构成比排序均相同,依次为:脾虚肝亢、脾虚痰聚、气郁化火、阴虚风动。
5.小儿多发性抽动症治疗中药使用规律
对纳入观察的640份病例处方进行分析,共涉及药物153种,其中出现频数在100次以上的有31种,使用频率在前十位的依次为防风469次、地龙418次、木瓜381次、伸筋草378次、谷精草318次、菊花305次、荆芥303次、葛根298次、柴胡295次、钩藤283次,其次是石菖蒲283次、半夏275次、陈皮273次、胆星266次、白芍257次、广郁金250次、知母246次、夏枯草213次、山药212次、茯苓200次、炒白术181次、党参160次等。六君子汤合泻青丸中的各药物在治疗多发性抽动症的药物使用频数中均出现频繁,主要药物的使用频率均在150次以上。
6.亚氨基二丙腈(IDPN)诱导多发性抽动症小鼠模型的行为学评价
经自主活动仪计数、点头次数及爬杆时间测定,发现腹腔注射亚氨基二丙腈诱导多发性抽动症小鼠模型不仅在表现效度上较好地模拟了人类多发性抽动症的临床表现(主要为头和颈部的动作过多),而且具有操作方法较简便,复制成功率高,症状维持时间长等优点,为进一步研究多发性抽动症提供了模型基础。
7.复方中药对TS模型鼠行为学改变的影响
以IDPN诱导的头部抽动动物模型为基础,通过自主活动仪计数、点头次数及爬杆时间测定,比较了复方中药六君子汤合泻青丸与泰必利对小鼠行为的改变。用药后小鼠的自主活动较模型组均降低,且从长期疗效来看,复方中药抑制抽动的效果更优于泰必利。
结论:
1.多发性抽动症以学龄期7～13~-岁发病率最高。
2.男孩的发病率较女孩高。
3.在中医证型分布中,以脾虚肝亢最为多见。其次为脾虚痰聚、气郁化火及阴虚风动。故临床以扶土抑木法为指导,运用六君子汤合泻青丸加味健脾平肝以治疗小儿多发性抽搐症具有理论依据和临床基础。
4.导师王素梅教授治疗多发性抽动症患儿的640份病例处方中,共涉及药物153种,其中出现频数在100次以上的有31种,使用频率在前十位的依次为防风469次、地龙418次、木瓜381次、伸筋草378次、谷精草318次、菊花305次、荆芥303次、葛根298次、柴胡295次、钩藤283次,其次是石菖蒲283次、半夏275次、陈皮273次、胆星266次、白芍257次、广郁金250次、知母246次、夏枯草213次、山药212次、茯苓200次、炒白术181次、党参160次等。六君子汤合泻青丸中的各药物在治疗多发性抽动症的药物使用频数中均出现频繁,主要药物的使用频率均在150次以上。
5.亚氨基二丙腈诱导多发性抽动症小鼠模型较好地模拟了人类多发性抽动症的部分症状,是比较理想的多发性抽动症动物模型。
6.复方中药六君子汤合泻青丸可有效地抑制IDPN诱导的小鼠抽动,且从长期疗效来看,其作用更优于泰必利。
Objective
Discussed clinical characteristics and TCM-based distribution of children with Tourette syndrome,summarized rules of prescriptions which were used by Professor Wang Sumei,in order to provide the clinical foundation for Liujunzi Tang and Xiexing Wan.Evaluated the behavior of iminodipropionitrile (IDPN)-induced mouse model of Tourette syndrome and observed the impact of changes in behavior by herbal medicine,so as to provide experimental basis for clinic.
Methods
Investigated parents and children with TS using self-made "Tourette syndrome survey",including all the symptoms which were needed for TCM diagnosis.Set up TS animal model by intraperitoneal injection of IDPN and treated with Chinese medicine or Tiapridal.Tourette syndrome mice were evaluated by autonomic activities,head nutation and climbing time,and observated behavioral changes each.
Results
1.Tourette syndrome and gender
There were 322 boys and 93 girls in 415 cases of children with Tourette syndrome.Boys outnumbered girls in the ratio of 3.46 to 1,and this was consistent with previous literature reports.
2.Tourette syndrome and age
2.1 Age of onset
In 415 cases of children with Tourette syndrome which were collected according to the standard,the minimum onset age was 2 years old.The maximum was 16 and average age was(7.06±2.53).2 cases were in 2～3~- year-old period (0.48%).188 cases were 3～7~- year-old(45.30%).7～13~- year-old children were 215 cases(51.81%).13～16~- were 10 cases(2.41%).The highest incidence was onset when one was school age from 7 to 13.
2.2 Age of visiting
In this group,the visiting age distribution is 4～7~- year-old of 79 cases (19.04%),7～13~- year-old of 263 cases(63.37%),13～18~- year-old of 73 cases (17.59%),and the average age is(9.56±3.14) years old.
3.Tourette syndrome and course
The longest duration of children in the group was 12 years and the shortest less than one year.The average duration was(2.51±2.37) years.It can be seen that Tourette Syndrome lasted for long period and gradually attracted people' s attention.
4.Tourette syndrome and TCM syndrome distribution
The survey showed that splenic asthenia and liver domination was the most frequent TCM syndrome for Tourette syndrome.The mainly frequency was 172,which constitute more than 41.45%.It followed by spleen asthenia and poly-sputum, frequency of occurrence for 125,which constitute more than 30.12%.Next syndrome was stagnated QI transforming into fire,which happened in 109 cases and constituted more than 26.27%.Stirring of wind due to deficiency of YIN was the least,which only occurred on 9 chileren and constituted 2.17%.The investigator analyzed the relationship between gender and TCM syndrome,visiting age and TCM syndrome,found that boys and girls,different ages all had the same order in TCM syndrome.
5.Rules of Chinese medicine for Tourette syndrome
In the observation of more than 640 prescriptions,there were a total of 153 kinds of Chinese herbs and 31 kinds occurred more than 100 times.The most use of frequency were Fangfeng,used 469 times,and followed by Dilong,418 times, Mugua,381times,Shenjincao,378 times,Gujingcao,318 times,Juhua,305 times, Jingjie,303 times,Gegen,298 times,Chaihu,295 times,Gouteng,283times and so on.The herbs in Liujunzi Tang and Xieqing Wan occurred frequently,and main were all used more than 150 times.
6.Behavior evaluation of the mouse model of Tourette syndrome
Set up TS animal model by intraperitoneal injection of IDPN and evaluated by autonomic activities,head nutation and climbing time.The model had good quality in the performance of validity,easy operation,high rate for copy and maintenance of the symptoms for a long time.This method provided a model foundation for further research of Tourette syndrome.
7.Behavior changes of the TS model mice with compound Chinese medicine
Using the IDPN-induced animal model,compared changes of behavior caused by the Chinese medicine and Tiapridal.The Chinese medicine team and the Tiapridal team both have less action than the model.From a long time,Chinese medicine has better effect than Tiapridal.
Conclusion
1.Tourette syndrome has the highest incidence in school-age 7 to 13~- years old.
2.Incidence in boys is higher than girls.
3.Splenic asthenia and liver domination was the most frequent TCM syndrome for rourette syndrome.It followed by spleen asthenia and poly-sputum,stagnated QI transforming into fire and stirring of wind due to deficiency of YIN.According to invigorating the spleen and purging the green,we use Liujunzi Tang and Xieqing Wan for the treatment of multiple tic disorder in children.
4.In the observation of more than 640 prescriptions,there were a total of 153 kinds of Chinese herbs and 31 kinds occurred more than 100 times.The most use of frequency were Fangfeng,used 469 times,and followed by Dilong,418 times, Mugua,381 times,Shenjincao,378 times,Gujingcao,318 times,Juhua,305 times, Jingjie,303 times,Gegen,298 times,Chaihu,295 times,Gouteng,283 times and so on.The herbs in Liujunzi Tang and Xieqing Wan occurred frequently,and main were all used more than 150 times.
5.IDPN-induced Tourette syndrome mouse model simulates parts of the human Tourette's syndrome symptoms,and is a good animal model of Tourette syndrome.
6.Liujunzi Tang and Xieqing Wan has a good effect on the tics of the IDPN-induced animal model.From a long time,Chinese medicine is better than Tiapridal.
引文
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