培补肝肾复方治疗帕金森病及其肠功能障碍的疗效研究
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摘要
帕金森病是一种渐进发展的中枢神经系统变性疾病。该病的治疗目前无论药物治疗或手术治疗,只能改善其症状,不能阻止病情的发展,更无法治愈。外科治疗的费用及其适应证的局限性,药物治疗后异动症及症状波动等运动并发症的出现和药物及疾病本身带来的非运动副反应都是治疗PD亟待解决的问题。中药具有毒副作用小且通过辩证论治、从整体调节患者阴阳平衡的特点,进一步探究中医药治疗帕金森病的优势所在具有重要的意义。
本研究通过观察治疗前后帕金森病患者运动症状及非运动症状西医相关量表的分值变化及帕金森病便秘与功能性便秘患者CCK、Ghrelin分泌水平的差异性。同时,在MPTP经典造模的基础上,以鱼藤酮复制帕金森病模型,模拟“慢性小剂量灌胃给药致肠神经系统、迷走神经背核、黑质中间外侧核等全身多系统α-synuclein聚积”的致病过程,从质谱法、放射免疫法等水平观察脑、肠神经组织部分神经递质的含量及血清脑肠肽水平,同时以中药作为干预手段,探究培补肝肾复方对该动物模型脑、肠神经元的影响,明确其作用机制及环节。
本课题从肝肾论治,脑肠同治,通过对治疗前后运动症状及非运动症状2部分的量表评定,探究培补肝肾复方的疗效。同时在经典MPTP造模的基础上,模拟“慢性小剂量灌胃给药致全身多系统α-synuclein聚积”的PD致病过程,从CCK、Ghrelin含量的测定及粪便含水率测定观察PD小鼠的肠功能障碍,对PD脑、肠造模方法进行了创新。通过脑、胃、肠TH阳性细胞的表达及脑组织DA、HVA等神经递质含量的测定,探究培补肝肾复方对脑、胃、肠多巴胺神经元干预的机制。本研究的造模方法还需进一步探讨,是否能更好的模拟脑胃肠的变性及脑肠肽水平的影响因素还需进一步研究。
临床研究
[目的]探究中医药治疗帕金森病运动症状及非运动症状的疗效,以期为探究中医药治疗帕金森病的优势所在提供客观依据。
[方法]以Hoehn-Yahr分级为标准,采用分层随机化分组,将60例帕金森病患者随机分为治疗组与对照组,两组在原有抗PD西药治疗的基础上,治疗组加用培补肝肾复方治疗,对比治疗前后中医症状分值量表及帕金森病运动症状、非运动症状的相关量表,探究培补肝肾复方治疗帕金森病的疗效。同时对12例帕金森病便秘患者的血清CCK、Ghrelin含量进行测定,与功能性便秘患者进行比较,初步探究不同疾病的发病机制对部分脑肠肽分泌水平的影响。
[结果]1、帕金森病非运动症状可出现于疾病的任何一个阶段,部分早于运动症状前出现,便秘、睡眠障碍、嗅觉减退、感觉障碍及性功能障碍多在运动症状前出现。2、培补肝肾复方可明显改善患者的运动及非运动症状,非运动症状中以疲乏、便秘、嗜睡症状改善较为明显。3、帕金森病便秘患者存在脑肠肽分泌异常,且脑肠肽分泌水平与病情严重程度无相关性。帕金森病便秘与功能性便秘患者发病机制不同,Ghrelin分泌水平有差异。
[结论]培补肝肾复方可明显改善帕金森病的运动症状及非运动症状,对非运动症状中的帕金森病便秘及疲乏治疗有效。
实验研究
1、培补肝肾复方对PD小鼠行为学及形态学的影响
[目的]通过对PD小鼠的行为学及脑形态学观察,初步探究造模方法对小鼠行为学、形态学影响及中医药治疗PD的疗效。,探究中医药治疗对PD运动症状的疗效及病理形态学的影响
[方法]在MPTP造模的基础上,参考外文文献,以鱼藤酮模拟“慢性小剂量灌胃给药致肠神经系统、迷走神经背核、黑质中间外侧核等全身多系统α-synuclein聚积”的PD致病过程,从爬杆试验、悬挂试验、游泳试验、自主活动测定四方面对小鼠行为学进行观察,同时通过HE染色及免疫组化方法对脑形态学观察,探究中医药治疗对PD运动症状的疗效及病理形态学的影响。
[结果]1、鱼藤酮组小鼠造模符合模拟PD“病情进行性发展”的致病过程。2、RT与MPTP造模均可导致小鼠行为学改变,主要表现为动作迟缓,活动减少,反应能力减慢。给予培补肝肾中药治疗或抗PD西药美多芭治疗后可有所改善。3、模型组小鼠脑组织出现神经细胞变性,主要集中于黑质,培补肝肾中药及抗PD西药治疗后可改善部分神经细胞变性,从而改善PD症状。4、模型组小鼠脑组织TH阳性细胞减少,证实PD脑DA含量减少,给予培补肝肾中药及抗PD西药治疗后可从增加DA含量作用点来改善症状。[结论]培补肝肾复方可改善神经细胞变性,且通过增加DA含量来改善运动症状。
2、培补肝肾复方对PD小鼠粪便含水量及CCK、Ghrelin含量的影响
[目的]探究培补肝肾复方对PD模型脑肠肽含量的影响,明确脑肠肽含量对帕金森病便秘影响及中医药治疗的作用靶点。
[方法]本研究在经典MPTP造模的基础上,以鱼藤酮复制帕金森病模型,模拟“慢性小剂量灌胃给药致肠神经系统、迷走神经背核、黑质中间外侧核等全身多系统α-synuclein聚积”的致病过程,从粪便含水量及血浆CCK、Ghrelin含量测定观察PD小鼠的胃肠功能障碍,同时以中药作为干预手段,观察培补肝肾复方对该动物模型脑肠肽含量的影响。
[结果]1、RT及MPTP造模后均使小鼠存在便秘症状,给予中药培补肝肾复方治疗或抗PD西药美多芭治疗后可有所改善。2、RT组小鼠空白组、中药组、西药组CCK水平与模型组比较有差异,MPTP组小鼠CCK水平中药组与模型组和空白组之间均有差异,PD便秘的发病机制与CCK分泌水平有关,且培补肝肾复方可通过调节CCK分泌水平来改善便秘症状。3、MPTP模型组小鼠血浆CCK水平与脑DA含量呈正相关,考虑帕金森病黑质纹状体DA能神经元丢失过多的同时,部分脑-肠双项调节的胃肠激素如CCK分泌亦可能受到影响,造成PD小鼠肠功能障碍。4、RT组及MPTP组小鼠各组间Ghrelin值差异不明显,且血浆Ghrelin水平与脑DA含量无相关性。
[结论]PD小鼠造模后存在便秘症状,可能与帕金森病黑质纹状体DA能神经元丢失过多的同时,CCK分泌受到影响导致便秘有关,培补肝肾复方可通过调节CCK分泌水平来改善便秘症状。
3、培补肝肾复方对PD小鼠纹状体DA、HVA、5-HT、Ach含量的影响
[目的]通过测定不同干预方法中小鼠脑组织中DA、Ach、5-HT、HVA的含量,探究PD对部分神经递质含量的影响及中医药治疗的疗效。
[方法]本研究以RT及MPTP造模,从PD发病机制上模拟PD病理及神经生化学变化,由于组织样本中含有多种干扰物质,故采用液液萃取检测待测物中DA、Ach、5-HT、HVA的含量,采用液相串联质谱法测定DA、5-HT、Ach、HVA的浓度。通过测定不同干预方法中小鼠脑组织中DA、Ach、5-HT、HVA的含量,探究PD对部分神经递质含量的影响及中医药治疗的疗效。
[结果]1、RT及MPTP造模均可使脑组织DA及其代谢产物HVA含量降低,符合PD病理改变导致的纹状体DA神经递质不足。2、PD早期Ach及5-HT含量变化不如DA明显,可能与Ach在基底节中变化不明显有关,亦可能与PD分期,中晚期才累及精神、认知、睡眠障碍有关。3、培补肝肾复方中药及抗PD西药美多芭可提高脑组织DA及HVA含量,且中药应用主要通过提高DA代谢产物HVA含量从而增加DA含量。4、氯仿虽可提高大脑皮层中DA的含量,但对RT及MPTP小鼠空白组DA及HVA含量影响无差异,不影响中药组及西药组疗效判定。
[结论]RT及MPTP可通过降低脑组织DA及其代谢产物HVA含量来产生PD症状,培补肝肾复方可通过提高DA代谢产物HVA含量从而增加DA含量。
Parkinson's disease is a progressive degenerative disorder of the central nervous system. The treatment of the disease at present regardless of medication or operation treatment, can improve the symptoms, development cannot prevent the disease, can not cure. Surgical treatment of costs and adapt to the limitations of non-motor side effects, drug treatment of complications and symptoms of dyskinesia fluctuation movement and medicine and disease itself brings is the treatment of PD problems. Traditional Chinese medicine has little toxic side effect and through the dialectical theory of governance, regulating the balance of yin and Yang from the overall characteristics of the patients, further research of trad it ional Chinese medicine in the treatment of Parkinson's disease has important significance of advantage.
This study by observing the differences before and after treatment in patients with Parkinson disease symptoms and non-motor symptoms of western scale score change and Parkinson's disease with constipation of functional constipation in patients with CCK, Ghrelin and other parts of brain gut peptide secretion level of. At the same time, based on the classic MPTP model made by rotenone, copy the model of Parkinson's disease, the pathogenic process simulation "chronic low dose administered orally to the enteric nervous system, dorsal vagal nucleus, substantia nigra intermediolateral nucleus such as multi-body system of α-synuclein accumulation", from mass spectrometry, radioimmunoassay and observation on the level of brain enteric nervous tissue, partial neurotransmitter content and serum ghrelin level, at the same time with Chinese traditional medicine as a means of intervention, of compound peibuganshen effects on the animal model of cerebral, enteric neurons, clear the mechanism of action and the link.
The clinical research
[Objective] to explore effect of TCM treatment of Parkinson's disease and motor symptoms non-motor symptoms, in order to provide objective basis for exploring the advantages of TCM treatment of Parkinson's disease.
[Methods] the Hoehn-Yahr grading standard, stratified randomization,60cases of Parkinson's disease patients were randomly divided into treatment group and control group, two groups based on the original PD western medicine treatment, the treatment group was treated with compound peibuganshen treatment, the relevant comparison before and after treatment of TCM symptom score scale and Parkinson's disease symptoms, non-motor symptoms, curative effect of compound peibuganshen treatment of Parkinson's disease. At the same time,12cases of const ipat ion in pat ient s with Parkinson's disease, serum CCK Ghrelin levels were measured, compared with patients with functional constipation, influence the pathogenesis of preliminary inquiry of different diseases on the secretion of some brain gut peptide.
[results]1, non-motor symptoms of Parkinson's disease and can appear in any one stage of the disease, part appeared earlier than before motor symptoms, sleep disorders, constipation, loss of sense of smell, sensory disturbance and sexual dysfunction in motion before symptoms appear.2, compound peibuganshen can significantly improve the patient's motor and non-motor symptoms, non-motor symptoms of fatigue, constipation, drowsiness symptoms improved obviously.3, Parkinson's disease with constipation in ghrelin secretion, and no correlation between ghrelin secretion levels with severity. Parkinson's disease with constipation and functional constipation in patients with different pathogenesis, there are differences in Ghrelin secretion level.
[Conclusion] compound peibuganshen can significantly improve Parkinson's disease, Parkinson's disease with constipation and effective on the treatment of non-motor symptoms of fatigue.
The experimental study
1. compound peibuganshen effect on PD mice behavior and morphology
[Objective] through observation and brain pathology in PD mice behavior, effect of preliminary inquiry model of mice behavior, morphology and the influence of the TCM treatment of PD. Research of traditional Chinese medicine, treatment of PD motor symptoms and pathological changes of
[method] Based on MPTP modeling, the reference of foreign literature,"PD pathogenic process of chronic low dose administered orally to the enteric nervous system, dorsal vagal nucleus, substantia nigra intermediolateral nucleus such as multi-body system of α-synuclein accumulation" to rotenone, determination of the Quartet from the pole test, test, suspension swimming test, autonomic activity in mice behavior were observed, and through HE staining and immunohistochemical methods on brain morphology observation, to explore Chinese medicine in the treatment of PD symptoms and pathological changes of
[results]1, rotenone group mice model with simulated PD "pathogenesis of disease development.".2, RT and MPTP in mice model can lead to behavioral changes, mainly for the slow movement, reduced activity, reaction ability to slow down. Given the Chinese herbs treatment or anti PD medicine Madopar treatment can improve.3, the model group mice brain nerve cell degeneration, mainly in the substantia nigra, Chinese herbs and Western medicine treatment can improve the resistance of PD modified parts of nerve cells, thereby improving the symptoms of PD.4, model of brain tissue in mice TH positive cells decreased, that reduce the content of DA in brain PD, giving the Chinese herbs and Western medicine in the treatment of anti PD can increase the content of DA effect from point to improve symptoms.
[Conclusion] compound peibuganshen can improve the degeneration of nerve cells, and by increasing the DA content to improve motor symptoms.
2, effects of compound peibuganshen on PD mice fecal water content and CCK, Ghrelin content
[Objective]To explore the effect of compound peibuganshen on PD model of brain-gut peptide content, target clear influence brain gut peptide content in Parkinson's disease with constipation and treated by Chinese medicine.
[method] this study based on the classical MPTP model, in order to rotenone replication model of Parkinson's disease, the pathogenic process simulation "chronic low dose administered oral ly to the enteric nervous system, dorsal vagal nucleus, substantia nigra intermediolateral nucleus such as multi-body system of α-synuclein accumulation", from the feces of water and plasma gastrointestinal dysfunction of PD mice by CCK, the content of Ghrelin, at the same time with Chinese traditional medicine as a means of intervention, to observe the effect of compound peibuganshen on the animal model of brain gut peptide content
[results]1, RT and MPTP after modeling the mice constipation symptoms, give the traditional Chinese medicine compound peibuganshen treatment or anti PD medicine Madopar treatment can improve.2, RT group mice in blank group, Chinese medicine group, western medicine group CCK levels compared with the model group has difference, have differences between MPTP mice CCK traditional Chinese medicine group and the model group and blank group, associated with the pathogenesis of CCK PD constipation secretion, and compound peibuganshen by adjusting the CCK bleeding flat to improve the symptoms of constipation.3mice in MPTP model group, plasma CCK levels and brain DA content was positively related to Parkinson's disease, considering the nigrostriatal DA neurons lost too much at the same time, a part of the brain-gut double regulating gastrointestinal hormones such as CCK secretion also may be affected, resulting in PD mice intestinal dysfunction.4, RT group and MPTP group were observed between Ghrelin values were not significantly different, and the level of plasma Ghrelin and DA content in cerebral no correlation.
[conclusion]PD in constipation model mice, may be associated with Parkinson's disease nigrostriatal DA neurons lost too much at the same time, CCK secretion is affected by lead to constipation, compound peibuganshen by regulating CCK secretion levels to improve the symptoms of constipation.
3, compound peibuganshen effect on PD mouse striatum DA, HVA,5-HT, Ach content
[Objective] by determining the content of different interventions and in brain tissue of the rats with DA, Ach,5-HT, HVA, explore the effect of PD effects on neurotransmitters part of the nerve and the treatment of Chinese medicine.
[Method] in this study, RT and MPTP model, the PD pathology and neurobiochemical changes from the pathogenesis of PD simulation, because the tissue samples containing various interfering substances, the content of DA, Ach,5-HT, HVA measured liquid-liquid extraction and detection, concentration by liquid-phase tandem mass spectrometry method for the determination of DA,5-HT, Ach, HVA. The content of brain tissue was measured with different intervention methods of small rats, Ach,5-HT, DA, HVA, explore the effect of PD on neurotransmitters in effect part of the nerve and the treatment of Chinese medicine.
[results]1, RT and MPTP model can be reduced to brain tissue DA and its metabolite HVA in PD, consistent with pathological changes of striatal DA neurotransmitter insufficient. In2, PD in early Ach and the changes of5-HT content than DA significantly, and Ach in the basal ganglia of change is not obvious, may also be related to PD stage, the late involvement of spirit, cognition, sleep disorder.3, pnlk and anti PD medicine beauty Duobake increased the content of DA and HVA in brain tissue, and the traditional Chinese medicine used mainly by increasing the content of HVA DA metabolite thus increasing DA content.4, it could increase the content of chloroform in the cerebral cortex of DA, but no difference between the effects on RT and MPTP mice in blank group DA and HVA content, does not affect the curative effect of the traditional Chinese medicine group and Western medicine group decision.
[Conclusion]RT and MPTP can generate PD symptoms by reducing brain tissue DA and its metabolite HVA content, compound peibuganshen can increase HVA content of metabolites of DA and increase the content of DA.
本研究通过观察治疗前后帕金森病患者运动症状及非运动症状西医相关量表的分值变化及帕金森病便秘与功能性便秘患者CCK、Ghrelin分泌水平的差异性。同时,在MPTP经典造模的基础上,以鱼藤酮复制帕金森病模型,模拟“慢性小剂量灌胃给药致肠神经系统、迷走神经背核、黑质中间外侧核等全身多系统α-synuclein聚积”的致病过程,从质谱法、放射免疫法等水平观察脑、肠神经组织部分神经递质的含量及血清脑肠肽水平,同时以中药作为干预手段,探究培补肝肾复方对该动物模型脑、肠神经元的影响,明确其作用机制及环节。
本课题从肝肾论治,脑肠同治,通过对治疗前后运动症状及非运动症状2部分的量表评定,探究培补肝肾复方的疗效。同时在经典MPTP造模的基础上,模拟“慢性小剂量灌胃给药致全身多系统α-synuclein聚积”的PD致病过程,从CCK、Ghrelin含量的测定及粪便含水率测定观察PD小鼠的肠功能障碍,对PD脑、肠造模方法进行了创新。通过脑、胃、肠TH阳性细胞的表达及脑组织DA、HVA等神经递质含量的测定,探究培补肝肾复方对脑、胃、肠多巴胺神经元干预的机制。本研究的造模方法还需进一步探讨,是否能更好的模拟脑胃肠的变性及脑肠肽水平的影响因素还需进一步研究。
临床研究
[目的]探究中医药治疗帕金森病运动症状及非运动症状的疗效,以期为探究中医药治疗帕金森病的优势所在提供客观依据。
[方法]以Hoehn-Yahr分级为标准,采用分层随机化分组,将60例帕金森病患者随机分为治疗组与对照组,两组在原有抗PD西药治疗的基础上,治疗组加用培补肝肾复方治疗,对比治疗前后中医症状分值量表及帕金森病运动症状、非运动症状的相关量表,探究培补肝肾复方治疗帕金森病的疗效。同时对12例帕金森病便秘患者的血清CCK、Ghrelin含量进行测定,与功能性便秘患者进行比较,初步探究不同疾病的发病机制对部分脑肠肽分泌水平的影响。
[结果]1、帕金森病非运动症状可出现于疾病的任何一个阶段,部分早于运动症状前出现,便秘、睡眠障碍、嗅觉减退、感觉障碍及性功能障碍多在运动症状前出现。2、培补肝肾复方可明显改善患者的运动及非运动症状,非运动症状中以疲乏、便秘、嗜睡症状改善较为明显。3、帕金森病便秘患者存在脑肠肽分泌异常,且脑肠肽分泌水平与病情严重程度无相关性。帕金森病便秘与功能性便秘患者发病机制不同,Ghrelin分泌水平有差异。
[结论]培补肝肾复方可明显改善帕金森病的运动症状及非运动症状,对非运动症状中的帕金森病便秘及疲乏治疗有效。
实验研究
1、培补肝肾复方对PD小鼠行为学及形态学的影响
[目的]通过对PD小鼠的行为学及脑形态学观察,初步探究造模方法对小鼠行为学、形态学影响及中医药治疗PD的疗效。,探究中医药治疗对PD运动症状的疗效及病理形态学的影响
[方法]在MPTP造模的基础上,参考外文文献,以鱼藤酮模拟“慢性小剂量灌胃给药致肠神经系统、迷走神经背核、黑质中间外侧核等全身多系统α-synuclein聚积”的PD致病过程,从爬杆试验、悬挂试验、游泳试验、自主活动测定四方面对小鼠行为学进行观察,同时通过HE染色及免疫组化方法对脑形态学观察,探究中医药治疗对PD运动症状的疗效及病理形态学的影响。
[结果]1、鱼藤酮组小鼠造模符合模拟PD“病情进行性发展”的致病过程。2、RT与MPTP造模均可导致小鼠行为学改变,主要表现为动作迟缓,活动减少,反应能力减慢。给予培补肝肾中药治疗或抗PD西药美多芭治疗后可有所改善。3、模型组小鼠脑组织出现神经细胞变性,主要集中于黑质,培补肝肾中药及抗PD西药治疗后可改善部分神经细胞变性,从而改善PD症状。4、模型组小鼠脑组织TH阳性细胞减少,证实PD脑DA含量减少,给予培补肝肾中药及抗PD西药治疗后可从增加DA含量作用点来改善症状。[结论]培补肝肾复方可改善神经细胞变性,且通过增加DA含量来改善运动症状。
2、培补肝肾复方对PD小鼠粪便含水量及CCK、Ghrelin含量的影响
[目的]探究培补肝肾复方对PD模型脑肠肽含量的影响,明确脑肠肽含量对帕金森病便秘影响及中医药治疗的作用靶点。
[方法]本研究在经典MPTP造模的基础上,以鱼藤酮复制帕金森病模型,模拟“慢性小剂量灌胃给药致肠神经系统、迷走神经背核、黑质中间外侧核等全身多系统α-synuclein聚积”的致病过程,从粪便含水量及血浆CCK、Ghrelin含量测定观察PD小鼠的胃肠功能障碍,同时以中药作为干预手段,观察培补肝肾复方对该动物模型脑肠肽含量的影响。
[结果]1、RT及MPTP造模后均使小鼠存在便秘症状,给予中药培补肝肾复方治疗或抗PD西药美多芭治疗后可有所改善。2、RT组小鼠空白组、中药组、西药组CCK水平与模型组比较有差异,MPTP组小鼠CCK水平中药组与模型组和空白组之间均有差异,PD便秘的发病机制与CCK分泌水平有关,且培补肝肾复方可通过调节CCK分泌水平来改善便秘症状。3、MPTP模型组小鼠血浆CCK水平与脑DA含量呈正相关,考虑帕金森病黑质纹状体DA能神经元丢失过多的同时,部分脑-肠双项调节的胃肠激素如CCK分泌亦可能受到影响,造成PD小鼠肠功能障碍。4、RT组及MPTP组小鼠各组间Ghrelin值差异不明显,且血浆Ghrelin水平与脑DA含量无相关性。
[结论]PD小鼠造模后存在便秘症状,可能与帕金森病黑质纹状体DA能神经元丢失过多的同时,CCK分泌受到影响导致便秘有关,培补肝肾复方可通过调节CCK分泌水平来改善便秘症状。
3、培补肝肾复方对PD小鼠纹状体DA、HVA、5-HT、Ach含量的影响
[目的]通过测定不同干预方法中小鼠脑组织中DA、Ach、5-HT、HVA的含量,探究PD对部分神经递质含量的影响及中医药治疗的疗效。
[方法]本研究以RT及MPTP造模,从PD发病机制上模拟PD病理及神经生化学变化,由于组织样本中含有多种干扰物质,故采用液液萃取检测待测物中DA、Ach、5-HT、HVA的含量,采用液相串联质谱法测定DA、5-HT、Ach、HVA的浓度。通过测定不同干预方法中小鼠脑组织中DA、Ach、5-HT、HVA的含量,探究PD对部分神经递质含量的影响及中医药治疗的疗效。
[结果]1、RT及MPTP造模均可使脑组织DA及其代谢产物HVA含量降低,符合PD病理改变导致的纹状体DA神经递质不足。2、PD早期Ach及5-HT含量变化不如DA明显,可能与Ach在基底节中变化不明显有关,亦可能与PD分期,中晚期才累及精神、认知、睡眠障碍有关。3、培补肝肾复方中药及抗PD西药美多芭可提高脑组织DA及HVA含量,且中药应用主要通过提高DA代谢产物HVA含量从而增加DA含量。4、氯仿虽可提高大脑皮层中DA的含量,但对RT及MPTP小鼠空白组DA及HVA含量影响无差异,不影响中药组及西药组疗效判定。
[结论]RT及MPTP可通过降低脑组织DA及其代谢产物HVA含量来产生PD症状,培补肝肾复方可通过提高DA代谢产物HVA含量从而增加DA含量。
Parkinson's disease is a progressive degenerative disorder of the central nervous system. The treatment of the disease at present regardless of medication or operation treatment, can improve the symptoms, development cannot prevent the disease, can not cure. Surgical treatment of costs and adapt to the limitations of non-motor side effects, drug treatment of complications and symptoms of dyskinesia fluctuation movement and medicine and disease itself brings is the treatment of PD problems. Traditional Chinese medicine has little toxic side effect and through the dialectical theory of governance, regulating the balance of yin and Yang from the overall characteristics of the patients, further research of trad it ional Chinese medicine in the treatment of Parkinson's disease has important significance of advantage.
This study by observing the differences before and after treatment in patients with Parkinson disease symptoms and non-motor symptoms of western scale score change and Parkinson's disease with constipation of functional constipation in patients with CCK, Ghrelin and other parts of brain gut peptide secretion level of. At the same time, based on the classic MPTP model made by rotenone, copy the model of Parkinson's disease, the pathogenic process simulation "chronic low dose administered orally to the enteric nervous system, dorsal vagal nucleus, substantia nigra intermediolateral nucleus such as multi-body system of α-synuclein accumulation", from mass spectrometry, radioimmunoassay and observation on the level of brain enteric nervous tissue, partial neurotransmitter content and serum ghrelin level, at the same time with Chinese traditional medicine as a means of intervention, of compound peibuganshen effects on the animal model of cerebral, enteric neurons, clear the mechanism of action and the link.
The clinical research
[Objective] to explore effect of TCM treatment of Parkinson's disease and motor symptoms non-motor symptoms, in order to provide objective basis for exploring the advantages of TCM treatment of Parkinson's disease.
[Methods] the Hoehn-Yahr grading standard, stratified randomization,60cases of Parkinson's disease patients were randomly divided into treatment group and control group, two groups based on the original PD western medicine treatment, the treatment group was treated with compound peibuganshen treatment, the relevant comparison before and after treatment of TCM symptom score scale and Parkinson's disease symptoms, non-motor symptoms, curative effect of compound peibuganshen treatment of Parkinson's disease. At the same time,12cases of const ipat ion in pat ient s with Parkinson's disease, serum CCK Ghrelin levels were measured, compared with patients with functional constipation, influence the pathogenesis of preliminary inquiry of different diseases on the secretion of some brain gut peptide.
[results]1, non-motor symptoms of Parkinson's disease and can appear in any one stage of the disease, part appeared earlier than before motor symptoms, sleep disorders, constipation, loss of sense of smell, sensory disturbance and sexual dysfunction in motion before symptoms appear.2, compound peibuganshen can significantly improve the patient's motor and non-motor symptoms, non-motor symptoms of fatigue, constipation, drowsiness symptoms improved obviously.3, Parkinson's disease with constipation in ghrelin secretion, and no correlation between ghrelin secretion levels with severity. Parkinson's disease with constipation and functional constipation in patients with different pathogenesis, there are differences in Ghrelin secretion level.
[Conclusion] compound peibuganshen can significantly improve Parkinson's disease, Parkinson's disease with constipation and effective on the treatment of non-motor symptoms of fatigue.
The experimental study
1. compound peibuganshen effect on PD mice behavior and morphology
[Objective] through observation and brain pathology in PD mice behavior, effect of preliminary inquiry model of mice behavior, morphology and the influence of the TCM treatment of PD. Research of traditional Chinese medicine, treatment of PD motor symptoms and pathological changes of
[method] Based on MPTP modeling, the reference of foreign literature,"PD pathogenic process of chronic low dose administered orally to the enteric nervous system, dorsal vagal nucleus, substantia nigra intermediolateral nucleus such as multi-body system of α-synuclein accumulation" to rotenone, determination of the Quartet from the pole test, test, suspension swimming test, autonomic activity in mice behavior were observed, and through HE staining and immunohistochemical methods on brain morphology observation, to explore Chinese medicine in the treatment of PD symptoms and pathological changes of
[results]1, rotenone group mice model with simulated PD "pathogenesis of disease development.".2, RT and MPTP in mice model can lead to behavioral changes, mainly for the slow movement, reduced activity, reaction ability to slow down. Given the Chinese herbs treatment or anti PD medicine Madopar treatment can improve.3, the model group mice brain nerve cell degeneration, mainly in the substantia nigra, Chinese herbs and Western medicine treatment can improve the resistance of PD modified parts of nerve cells, thereby improving the symptoms of PD.4, model of brain tissue in mice TH positive cells decreased, that reduce the content of DA in brain PD, giving the Chinese herbs and Western medicine in the treatment of anti PD can increase the content of DA effect from point to improve symptoms.
[Conclusion] compound peibuganshen can improve the degeneration of nerve cells, and by increasing the DA content to improve motor symptoms.
2, effects of compound peibuganshen on PD mice fecal water content and CCK, Ghrelin content
[Objective]To explore the effect of compound peibuganshen on PD model of brain-gut peptide content, target clear influence brain gut peptide content in Parkinson's disease with constipation and treated by Chinese medicine.
[method] this study based on the classical MPTP model, in order to rotenone replication model of Parkinson's disease, the pathogenic process simulation "chronic low dose administered oral ly to the enteric nervous system, dorsal vagal nucleus, substantia nigra intermediolateral nucleus such as multi-body system of α-synuclein accumulation", from the feces of water and plasma gastrointestinal dysfunction of PD mice by CCK, the content of Ghrelin, at the same time with Chinese traditional medicine as a means of intervention, to observe the effect of compound peibuganshen on the animal model of brain gut peptide content
[results]1, RT and MPTP after modeling the mice constipation symptoms, give the traditional Chinese medicine compound peibuganshen treatment or anti PD medicine Madopar treatment can improve.2, RT group mice in blank group, Chinese medicine group, western medicine group CCK levels compared with the model group has difference, have differences between MPTP mice CCK traditional Chinese medicine group and the model group and blank group, associated with the pathogenesis of CCK PD constipation secretion, and compound peibuganshen by adjusting the CCK bleeding flat to improve the symptoms of constipation.3mice in MPTP model group, plasma CCK levels and brain DA content was positively related to Parkinson's disease, considering the nigrostriatal DA neurons lost too much at the same time, a part of the brain-gut double regulating gastrointestinal hormones such as CCK secretion also may be affected, resulting in PD mice intestinal dysfunction.4, RT group and MPTP group were observed between Ghrelin values were not significantly different, and the level of plasma Ghrelin and DA content in cerebral no correlation.
[conclusion]PD in constipation model mice, may be associated with Parkinson's disease nigrostriatal DA neurons lost too much at the same time, CCK secretion is affected by lead to constipation, compound peibuganshen by regulating CCK secretion levels to improve the symptoms of constipation.
3, compound peibuganshen effect on PD mouse striatum DA, HVA,5-HT, Ach content
[Objective] by determining the content of different interventions and in brain tissue of the rats with DA, Ach,5-HT, HVA, explore the effect of PD effects on neurotransmitters part of the nerve and the treatment of Chinese medicine.
[Method] in this study, RT and MPTP model, the PD pathology and neurobiochemical changes from the pathogenesis of PD simulation, because the tissue samples containing various interfering substances, the content of DA, Ach,5-HT, HVA measured liquid-liquid extraction and detection, concentration by liquid-phase tandem mass spectrometry method for the determination of DA,5-HT, Ach, HVA. The content of brain tissue was measured with different intervention methods of small rats, Ach,5-HT, DA, HVA, explore the effect of PD on neurotransmitters in effect part of the nerve and the treatment of Chinese medicine.
[results]1, RT and MPTP model can be reduced to brain tissue DA and its metabolite HVA in PD, consistent with pathological changes of striatal DA neurotransmitter insufficient. In2, PD in early Ach and the changes of5-HT content than DA significantly, and Ach in the basal ganglia of change is not obvious, may also be related to PD stage, the late involvement of spirit, cognition, sleep disorder.3, pnlk and anti PD medicine beauty Duobake increased the content of DA and HVA in brain tissue, and the traditional Chinese medicine used mainly by increasing the content of HVA DA metabolite thus increasing DA content.4, it could increase the content of chloroform in the cerebral cortex of DA, but no difference between the effects on RT and MPTP mice in blank group DA and HVA content, does not affect the curative effect of the traditional Chinese medicine group and Western medicine group decision.
[Conclusion]RT and MPTP can generate PD symptoms by reducing brain tissue DA and its metabolite HVA content, compound peibuganshen can increase HVA content of metabolites of DA and increase the content of DA.
引文
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[1]隆呈样.中医老年颤症诊断和疗效评定标准.北京中医学院学报,1992,15(4)：39.
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[1]Nobutaka A, Yoshio G. Evaluation of a 1-methyl-4-phenyl-1,2,3,6 tetrahydro pyridine (MPTP), treated C57 black mouse for parkinsonism[J]. BrainRes,1990, 515:57-63.
[2]施新猷,医学动物实验方法学[M].人民卫生出版社,1980,210.
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[1]谢俊霞,孙朝晖,蒋正尧等.CCK-8及损毁MFB对腹侧被盖区和伏核多巴胺、CCK-8含量的影响[J].2000,16(1)：13-16.
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[3]李林静,姜宏,王俊等.Ghrelin对MPTP小鼠帕金森病模型黑质TH、Bcl-2和Bax mRNA表达的影响[J].青岛大学医学院学报,2007,04：283-285.
[4]殷颖,曲瑞瑶.实验性帕金森病大鼠胃动力的研究[J].首都医科大学学报2002,23：144.