發(fā)布時(shí)間：2018-06-22 02:30

  本文選題：寧動(dòng)顆粒 + 抽動(dòng)-穢語(yǔ)綜合征�。� 參考：《山東大學(xué)》2012年博士論文

【摘要】：背景 抽動(dòng)-穢語(yǔ)綜合征(Tourette's syndrome, TS)是一種無(wú)意識(shí)的、無(wú)目的的、重復(fù)的刻板活動(dòng)為特征的神經(jīng)精神性疾病。臨床表現(xiàn)為頭面、腹部及四肢不自主的抽動(dòng),喉部發(fā)出奇特叫聲或者謾罵不避親疏為特征。TS有不規(guī)則的發(fā)作間歇期,有時(shí)可因轉(zhuǎn)移注意力而減輕,精神緊張時(shí)癥狀加重,睡眠時(shí)癥狀消失。 TS診斷標(biāo)準(zhǔn)為：1.具有多種運(yùn)動(dòng)性抽動(dòng)及一種或多種發(fā)聲性抽動(dòng),有時(shí)不一定在同一時(shí)間出現(xiàn)。2.抽動(dòng)每天發(fā)作多次,通常為一陣陣發(fā)作,病情持續(xù)或間斷發(fā)作已超過(guò)一年,其無(wú)抽動(dòng)間歇期連續(xù)不超過(guò)三個(gè)月。3.上述癥狀引起明顯的不安,顯著地影響社交、就業(yè)和其他重要領(lǐng)域的活動(dòng)。4.發(fā)病于18歲前。5.上述癥狀不是直接由某些藥物(如興奮劑)或內(nèi)科疾病(如亨廷頓舞蹈病或病毒感染后腦炎)引起。盡管TS是一種輕癥的神經(jīng)精神疾病,但病程遷延,反復(fù)發(fā)作,影響正常的生活和學(xué)習(xí)。 氟哌啶醇(Haloperidol, Hal)為DRD2阻滯劑,至今仍為治療TS的有效藥物。但氟哌啶醇的副作用相對(duì)較大,常見的副作用有嗜睡、鎮(zhèn)靜、乏力、頭昏、椎體外系反應(yīng)(如肌張力障礙、靜坐不能、帕金森氏病樣震顫等),服用數(shù)月后,可能出現(xiàn)類帕金森氏病的癥狀,如震顫、肌肉僵直等,長(zhǎng)期應(yīng)用氟哌啶醇可導(dǎo)致遲發(fā)性運(yùn)動(dòng)障礙的發(fā)生,表現(xiàn)為不自主的刻板運(yùn)動(dòng),并具有持續(xù)性。有如此多的副作用,一定程度上限制了該藥物的臨床應(yīng)用。 寧動(dòng)顆粒(Ningdong granule, NDG)是臨床治療TS的中藥復(fù)方制劑,已應(yīng)用于臨床多年,并顯示出良好的效果。前期研究表明,NDG可以明顯抑制TS癥狀的發(fā)生,但尚未與一線藥物氟哌啶醇及臨床常用的中西藥合用的療法進(jìn)行系統(tǒng)的對(duì)比觀察,遂行此番研究。 目的 1.觀察寧動(dòng)顆粒、氟哌啶醇及中西藥合用對(duì)TS患兒抽動(dòng)行為的影響。 2.三種治療方法在副反應(yīng)上有何異同,以期找出較為安全可靠的治療方案。 方法 將符合診斷標(biāo)準(zhǔn)的120(6-18歲)例患兒隨機(jī)分成NDG、Hal、NDG+Hal及control組各30例。NDG組予寧動(dòng)顆粒5mg/kg/d;氟哌啶醇,Hal組開始劑量為0.75mg/d,每2個(gè)星期增加1.5-3.0mg/d,最高劑量不超過(guò)4.5mg/d; NDG+Hal組予以同等劑量NDG與Hal合用,control組給予安慰劑治療,四組組均治療八周。參照美國(guó)耶魯綜合抽動(dòng)嚴(yán)重程度量表(Yale Global Tic Severity Scale, YGTSS)分別于治療的第0,2,4,6,8周進(jìn)行抽動(dòng)嚴(yán)重程度量化評(píng)估,以評(píng)定療效并記錄不良反應(yīng)。 結(jié)果 1.一般資料 在符合診斷標(biāo)準(zhǔn)的120例TS患兒中有3例患者治療過(guò)程中退出研究,其中control組2例,NDG組1例,在統(tǒng)計(jì)分析時(shí)將其剔除。兩組剩余117例患者在年齡、性別,差異均無(wú)統(tǒng)計(jì)學(xué)意義,具有可比性(P0.05)。 2. YGTSS評(píng)分比較 與治療前總抽動(dòng)、運(yùn)動(dòng)性抽動(dòng)、聲音性抽動(dòng)評(píng)分比較,NDG與Hal組治療后均顯著降低(P0.05),NDG+Hal組總抽動(dòng),發(fā)聲性抽動(dòng)和運(yùn)動(dòng)性抽動(dòng)評(píng)分降低更顯著,較control組差異具有統(tǒng)計(jì)學(xué)意義(P0.01)。 3.不良反應(yīng) Hal組與NDG+Hal組出現(xiàn)鎮(zhèn)靜作用、錐體外系反應(yīng)與QT間期延長(zhǎng)的副反應(yīng)明顯高于NDG組與control組(P0.05),NDG+Hal組中出現(xiàn)食欲亢進(jìn)、頭痛的幾率明顯高于control組(P0.05),Hal組出現(xiàn)焦慮癥狀的幾率較NDG組高(P0.05)。 結(jié)論 NDG與Hal均能有效改善TS抽動(dòng)癥狀。兩者合用療效優(yōu)單一治療,但寧動(dòng)顆粒臨床應(yīng)用副反應(yīng)小于氟哌啶醇。 背景 抽動(dòng)-穢語(yǔ)綜合征(Tourette's syndrome, TS)是一種無(wú)意識(shí)的、無(wú)目的的、重復(fù)的刻板活動(dòng)為特征的神經(jīng)精神性疾病。臨床表現(xiàn)為頭面、腹部及四肢不自主的抽動(dòng),喉部發(fā)出奇特叫聲或者謾罵不避親疏為特征。TS有不規(guī)則的發(fā)作間歇期,有時(shí)可因轉(zhuǎn)移注意力而減輕,精神緊張時(shí)癥狀加重,睡眠時(shí)癥狀消失。 目前,有關(guān)TS的病因及發(fā)病原因尚不十分明確,一般認(rèn)為TS的發(fā)病與遺傳基因和神經(jīng)遞質(zhì)系統(tǒng)異常相關(guān),腦外傷、感染、母親孕期的生活事件等生物、心理及環(huán)境因素也不可忽視,也有學(xué)者認(rèn)為該病具有明顯的家族聚集性,Leckman等提出遺傳因素、其它危險(xiǎn)和保護(hù)性因素與神經(jīng)生物學(xué)發(fā)育因素相互作用導(dǎo)致抽動(dòng)、強(qiáng)迫及其他抽動(dòng)相關(guān)癥狀的觀點(diǎn)。有關(guān)TS病理生理以及神經(jīng)生化研究,目前認(rèn)為發(fā)病與多巴胺或5-羥色胺及γ-氨基丁酸等神經(jīng)遞質(zhì)代謝異常相關(guān)�；蚺c相應(yīng)受體、載體功能異�；蛟诖竽X紋狀體表達(dá)異常關(guān)系密切。 臨床治療TS的中藥復(fù)方制劑寧動(dòng)顆粒(Ningdong granule, NDG),已經(jīng)應(yīng)用于臨床多年,效果良好。前期研究證明,NDG可以明顯抑制TS癥狀,但尚未與一線藥物氟哌啶醇及臨床常用的中西藥合用的療法進(jìn)行系統(tǒng)的對(duì)比觀察,遂行此番研究。 目的 1.觀察TS患兒血清中DA、5-TH、HVA、5-HIAA及GABA含量的變化,從神經(jīng)遞質(zhì)角度推斷TS的病因 2.觀察寧動(dòng)顆粒對(duì)TS患兒血清中DA、5-TH、HVA、5-HIAA及GABA含量的影響。探討寧動(dòng)顆粒治療TS的作用機(jī)制。 3.觀察NDG與氟哌啶醇的副作用及毒理作用。 方法 將符合診斷標(biāo)準(zhǔn)的120(6-18歲)例患兒隨機(jī)分成NDG、Hal、NDG+Hal及control組各30例。NDG組予寧動(dòng)顆粒5mg/kg/d;氟哌啶醇,Hal組開始劑量為0.75mg/d,每2個(gè)星期增加1.5-3.0mg/d,最高劑量不超過(guò)4.5mg/d; NDG+Hal組予以同等劑量NDG與Hal合用,control組給予安慰劑治療,四組組均治療八周。記錄不良反應(yīng),治療后檢測(cè)肝腎功能,以評(píng)價(jià)安全性。另募集30例健康查體患兒作為空白對(duì)照組。 結(jié)果 1.一般資料 在符合診斷標(biāo)準(zhǔn)的120例TS患兒中有4例患者治療過(guò)程中退出研究,其中control組2例,NDG組1例,Hal組1例,在統(tǒng)計(jì)分析時(shí)將其剔除。五組剩余146例兒童在年齡、性別,差異均無(wú)統(tǒng)計(jì)學(xué)意義,具有可比性(P0.05)。 2.血清中DA和HVA含量比較 五組兒童血清中DA含量在治療后無(wú)明顯差異(P0.05),而NDG+Hal (66.25±12.88ng/ml)、NDG (67.07±16.01ng/ml)及Hal (60.88±11.71ng/ml)組中HVA含量明顯高于control組(47.13±7.58ng/ml), control組中HVA含量顯著高于空白對(duì)照組(37.25±5.06ng/ml)(P0.05), NDG+Hal組與NDG組有顯著差異(p0.01)。NDG+Hal組中HVA含量亦高于Hal組(p0.05)。 3.血清中5-TH與5-HIAA含量的比較 經(jīng)研究表明,control、NDG、Hal及NDG+Hal四組兒童血清中5-TH與5-HIAA的含量均無(wú)顯著性差異(P0.05)。Control組血清中5-HIAA含量(11.41±1.61ng/ml)明顯高于空白對(duì)照組(7.66±1.08ng/m1)P0.05,兩組中5-TH無(wú)顯著性差異(P0.05)。 4.血清中GABA的含量比較 ELSAL結(jié)果顯示,NDG+Hal (166.22±41.91pmol/ml)、NDG (123.69±38.47pmol/ml)及Hal (113.97±36.23pmol/ml)組中GABA含量明顯高于control組(85.63±33.69pmol/ml)(P0.05), NDG+Hal組與NDG組有顯著差異(p0.01)。NDG+Hal組中GABA含量亦高于Hal組(p0.05)。control組中GABA含量顯著高于空白對(duì)照組(52.1655±29.78pmol/ml)(p0.05) 5.肝腎功能檢測(cè) Hal與NDG+Hal組血清中ALT含量明顯高于control組(p0.05)。 結(jié)論： 1.TS的發(fā)病與DA,5-TH及GABA系統(tǒng)存在聯(lián)系。 2.經(jīng)NDG與Hal治療后,患兒血清中HVA及GABA含量均升高,可推測(cè),NDG與Hal對(duì)TS的治療機(jī)制可能是增加了DA的代謝,并直接或間接地興奮GABA系統(tǒng)。
[Abstract]:background
Tourette's syndrome (TS) is a neuropsychiatric disorder characterized by an unconscious, aimless, repeated stereotyped activity. The clinical manifestation is the head, the involuntary twitch of the abdomen and extremities, the unusual cries or abuses of the larynx, and the irregular intermittence of the.TS. Attentions were relieved, symptoms increased during mental stress, and symptoms disappeared during sleep.
The TS diagnostic criteria are: 1. with multiple motor movements and one or more vocal twitches, sometimes not necessarily at the same time.2. seizures many times a day, usually a array of episodes, continuous or intermittent episodes for more than one year, and the absence of tash intermittence for no more than three months.3.. A significant impact on social, employment, and other important areas of activity.4. onset before the age of 18, the above symptoms of.5. are not directly caused by certain drugs (such as stimulants) or internal medical diseases (such as Huntington chorea or viral encephalitis). Although TS is a mild neuropsychiatric disease, the course of the disease is prolonged, repeated attacks, affecting normal life. And study.
Haloperidol (Hal) is a DRD2 blocker and is still an effective drug for the treatment of TS. However, the side effects of haloperidol are relatively large. The common side effects are somnolence, sedative, fatigue, dizziness, extrapycorp reaction (such as dystonia, sitting cannot, Parkinson's disease like tremor, etc.). After taking a few months, it may appear like Parkinson's disease. Symptoms such as tremor, muscle stiffness and so on, long term use of haloperidol can lead to the occurrence of delayed dyskinesia, characterized by involuntary stereotyped exercise and persistent. There are so many side effects that limit the clinical application of the drug to a certain extent.
Ningdong granule (NDG) is a traditional Chinese medicine compound preparation for the clinical treatment of TS. It has been applied to clinical years and has shown good results. Earlier studies have shown that NDG can obviously inhibit the occurrence of TS symptoms, but it has not been compared with the first-line haloperidol and the commonly used traditional Chinese and Western medicine. This is the study.
objective
1. to observe the effects of Ningdong granule, haloperidol and Chinese and Western Medicine on TiC behavior in children with TS.
2. what is the difference between the three treatments on side effects in order to find a safer and more reliable treatment plan?
Method
120 (6-18 year old) children were randomly divided into NDG, Hal, NDG+Hal and group control, 30 cases of.NDG group were given Ningjing granule 5mg/kg/d, haloperidol, Hal group began to dose 0.75mg/d, increase 1.5-3.0mg/d every 2 weeks, the highest dose was not more than 4.5mg/d. Treatment, the four groups were treated for eight weeks. Yale Global Tic Severity Scale (YGTSS) was used to evaluate the severity of aspiration severity on week 0,2,4,6,8, respectively, to evaluate the efficacy and record adverse reactions.
Result
1. general information
In 120 cases of TS children with diagnostic criteria, 3 cases were withdrawn during the treatment process, of which 2 cases in group control and 1 cases in group NDG were eliminated in statistical analysis. The remaining 117 patients in the two group were not statistically significant in age, sex, and had comparability (P0.05).
2. YGTSS score comparison
Compared with the total aspiration before treatment, motor aspiration and sound aspiration score, the NDG and Hal groups were significantly decreased after treatment (P0.05). The total aspiration of group NDG+Hal, sounding aspiration and motor drive score decreased more significantly, compared with the control group, the difference was statistically significant (P0.01).
3. adverse reactions
Group Hal and group NDG+Hal had a sedative effect. The side effects of the extrapyramidal reaction and the prolongation of QT interval were significantly higher than those in the group NDG and the control group (P0.05). The incidence of hyperactivity in the NDG+Hal group was higher than that of the control group (P0.05), and the risk of anxiety in the Hal group was higher than that in the NDG group (P0.05).
conclusion
Both NDG and Hal can effectively improve TS tic symptoms. The combination of them is effective and single treatment, but the side effect of Ningdong granule is less than haloperidol.
background
Tourette's syndrome (TS) is a neuropsychiatric disorder characterized by an unconscious, aimless, repeated stereotyped activity. The clinical manifestation is the head, the involuntary twitch of the abdomen and extremities, the unusual cries or abuses of the larynx, and the irregular intermittence of the.TS. Attentions were relieved, symptoms increased during mental stress, and symptoms disappeared during sleep.
At present, the causes and causes of TS are still not very clear. It is generally believed that the pathogenesis of TS is associated with genetic and neurotransmitter systems, brain trauma, infection, life events in the mother's pregnancy and other biological, psychological and environmental factors, and some scholars believe that the disease has obvious familial aggregation, Leckman and so on. Factors, other risk and protective factors that interact with neurobiological developmental factors that lead to twitch, compulsion, and other aspiration related symptoms. TS pathophysiology and neurobiochemical studies are currently considered to be associated with abnormal metabolic abnormalities such as dopamine or 5- serotonin and gamma aminobutyric acid. Abnormal body function or abnormal expression in the striatum of the brain is closely related.
Ningdong granule (NDG), a Chinese medicine compound, has been used for many years in clinical treatment of TS, and has been applied for many years. The previous study has proved that NDG can obviously inhibit the symptoms of TS, but it has not been compared with the first-line haloperidol and the commonly used Chinese and Western Medicine.
objective
1. to observe the changes of DA, 5-TH, HVA, 5-HIAA and GABA contents in serum of children with TS, and to deduce the etiology of TS from the angle of neurotransmitters.
2. to observe the effect of Ningdong Granule on the contents of DA, 5-TH, HVA, 5-HIAA and GABA in serum of children with TS, and to explore the mechanism of Ningdong granule in treating TS.
3. to observe the side effects and toxicological effects of NDG and haloperidol.
Method
120 (6-18 year old) children were randomly divided into NDG, Hal, NDG+Hal and group control, 30 cases of.NDG group were given Ningjing granule 5mg/kg/d, haloperidol, Hal group began to dose 0.75mg/d, increase 1.5-3.0mg/d every 2 weeks, the highest dose was not more than 4.5mg/d. Treatment, the four groups were treated for eight weeks. The adverse reactions were recorded, the liver and kidney function was detected after treatment, and the safety was evaluated. 30 cases of healthy children were collected as the blank control group.
Result
1. general information
In 120 cases of TS children with diagnostic criteria, 4 patients withdrew from the treatment process, of which 2 cases in group control, 1 in group NDG and 1 in group Hal were eliminated in statistical analysis. The remaining 146 children in the five group were not statistically significant in age, sex, and had comparability (P0.05).
Comparison of the content of DA and HVA in 2. serum
There was no significant difference in the serum DA content between the five groups (P0.05), while NDG+Hal (66.25 + 12.88ng/ml), NDG (67.07 + 16.01ng/ml) and Hal (60.88 + 11.71ng/ml) groups were significantly higher than the control group (47.13 + 7.58ng/ml), and the content of the control group was significantly higher than that in the blank control group (37.25 +). Significant difference (P0.01) in group.NDG+Hal, the content of HVA was also higher than that in group Hal (P0.05).
Comparison of the content of 5-TH and 5-HIAA in 3. serum
The results showed that there was no significant difference between the serum levels of 5-TH and 5-HIAA in the four groups of children with control, NDG, Hal and NDG+Hal (P0.05), the content of 5-HIAA (11.41 + 1.61ng/ml) in the serum of.Control group was significantly higher than that of the blank control group (7.66 + 1.08ng/m1) P0.05, and there was no significant difference in the two groups.
Comparison of the content of GABA in 4. serum
The results of ELSAL showed that the content of GABA in NDG+Hal (166.22 + 41.91pmol/ml), NDG (123.69 + 38.47pmol/ml) and Hal (113.97 + 36.23pmol/ml) group was significantly higher than that of the control group (85.63 + 33.69pmol/ml), and the content of the NDG+Hal group was significantly higher than that of the empty group. White control group (52.1655 + 29.78pmol/ml) (P0.05)
5. liver and kidney function test
Serum ALT levels in group Hal and group NDG+Hal were significantly higher than those in group control (P0.05).
Conclusion:
The incidence of 1.TS is associated with the DA, 5-TH and GABA systems.
2. after the treatment of NDG and Hal, the serum levels of HVA and GABA increased in the children. It is possible to speculate that the mechanism of NDG and Hal for TS may be to increase the metabolism of DA and to stimulate the GABA system directly or indirectly.
【學(xué)位授予單位】：山東大學(xué)
【學(xué)位級(jí)別】：博士
【學(xué)位授予年份】：2012
【分類號(hào)】：R749.94

【參考文獻(xiàn)】

相關(guān)期刊論文 前10條

1 程安瑋;金征宇;萬(wàn)發(fā)春;;甘草多糖對(duì)小鼠脾淋巴細(xì)胞的免疫作用[J];安徽農(nóng)業(yè)科學(xué);2007年06期

2 艾小文;趙玉屏;;中西藥治療兒童抽動(dòng)-穢語(yǔ)綜合征療效比較[J];中華中醫(yī)藥雜志;2005年12期

3 盧銀平;董繼華;劉朝;管世鶴;;抽動(dòng)-穢語(yǔ)綜合征兒童巨細(xì)胞病毒感染的意義初探[J];中華神經(jīng)醫(yī)學(xué)雜志;2006年11期

4 戴筱青,陳江華,劉玉生;牡蠣提取物對(duì)小鼠T淋巴細(xì)胞功能的影響[J];第一軍醫(yī)大學(xué)學(xué)報(bào);1997年02期

5 李樹華,龐保東,徐應(yīng)軍,曹麗華,劉寅,吳家驊;抽動(dòng)-穢語(yǔ)綜合征危險(xiǎn)因素的病例對(duì)照研究[J];中國(guó)兒童保健雜志;2004年05期

6 陳文,林廣裕,吳毅;低鐵血癥對(duì)小兒多發(fā)性抽動(dòng)癥發(fā)病的影響[J];廣東醫(yī)學(xué);2003年06期

7 董澤平;硒與腫瘤研究的一些進(jìn)展[J];國(guó)外醫(yī)學(xué)(醫(yī)學(xué)地理分冊(cè));1995年02期

8 劉智勝;Tourette綜合征的遺傳學(xué)研究進(jìn)展[J];國(guó)外醫(yī)學(xué).神經(jīng)病學(xué)神經(jīng)外科學(xué)分冊(cè);1998年05期

9 楊宏宇,皇甫恩,譚慶榮;抽動(dòng)-穢語(yǔ)綜合征的遺傳學(xué)研究進(jìn)展[J];國(guó)外醫(yī)學(xué).精神病學(xué)分冊(cè);2001年04期

10 王少為;人體必需微量元素——硒[J];廣東微量元素科學(xué);1999年06期

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