帕病1号方治疗早期帕金森病的临床研究及作用机制探讨
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摘要
帕金森病(Parkinson's diseaes, PD)是多发于中老年人的神经系统变性疾病,其病因、发病机制尚未完全清楚。目前西药复方左旋多巴制剂仍然是治疗帕金森病的“金标准”,但因长期治疗存在严重的副作用及并发症,故中药治疗帕金森病日益为人们所重视。导师雒晓东教授总结出治疗PD的经验方帕病1号方,本课题立足于临床与实验两方面进行研究。临床研究部分观察帕病1号方对早期强直性帕金森病患者的运动功能、中医证候、生存质量及睡眠质量的改善情况,客观评价帕病1号方治疗早期强直性帕金森病的临床疗效。实验研究部分用6-羟基多巴(6-OHDA)单侧纹状体两点注射法制作帕金森病大鼠模型,通过病理形态学、生化检测、免疫组化等方法,从抗氧化应激、Akt信号通路抑制神经细胞凋亡等方面对帕病1号方治疗帕金森病的作用机制进行了研究。本课题分为四部分,摘要如下：
第一部分帕病1号方对强直少动型早期帕金森病的临床观察
目的：
观察帕病1号方对强直少动型早期帕金森病的临床疗效。
方法：
将55例早期帕金森病患者随机分为2组,治疗组27例予帕病1号方治疗,对照组28例予美多芭治疗,疗程均为2个月；疗程结束后进行疗效评价,疗效评价指标为帕金森病量表(UPDRS)第三部分(运动功能)、帕金森病生存质量量表(PDQ-39)、帕金森病中医证候积分量表、睡眠量表(PDSS)评分相对于基线的变化,同时观察血压、脉搏、血尿常规、肝肾功能、心电图及不良反应等。
结果：
1.在改善运动功能方面,帕病1号方组27例患者,显效25.93%(7/27),有效62.96%(17/27),总有效率88.89%；美多巴组28例患者,显效28.57%(8/28),有效57.14%(16/28),总有效率85.71%,两组显效有效率比较差异无统计学意义(P>0.05)。帕病1号方组、美多芭组的UPDRSⅢ积分治疗前后比较均有显著性差异(P<0.01)；两组组间比较无差异性(P>0.05)。提示在改善早期PD患者运动功能方面,中药复方帕病1号方与美多巴疗效相当。
2.在改善生活质量方面,帕病1号方组27例患者,显效29.63%(8/27),有效55.56%(15/27),总有效率85.19%；美多巴组28例患者,显效14.29%(4/28),有效46.43%(13/28),总有效率60.71%,两组显效有效率比较差异有统计学意义(P<0.05)；帕病1号方组、美多芭组两组治疗前后生活质量积分比较均有显著性差异(P<0.01)；两组组间比较亦存在显著性差异(P<0.05),说明帕病1号方和美多芭均可改善早期帕金森病患者生活质量,但帕病1号方疗效优于美多芭组。
3.在改善中医症候方面,帕病1号方组27例患者,显效25.93%(7/27),有效59.26%(16/27),总有效率85.19%；美多巴组28例患者,显效13.33%(2/28),有效46.67%(15/28),总有效率60.71%,两组显效有效率比较差异有统计学意义(P<0.05)；帕病1号方组、美多芭组两组治疗前后中医症候积分比较均有显著性差异(P<0.01)；两组组间比较亦存在显著性差异(P<0.01)。说明帕病1号方和美多芭均可改善早期帕金森病患者中医症候,但帕病1号方疗效优于美多芭组。
4.在改善睡眠质量方面,帕病1号方组、美多芭组两组治疗前后睡眠质量积分比较均有显著性差异(P<0.01)；两组组间比较亦存在显著性差异(P<0.05)。说明帕病1号方和美多芭均可改善早期帕金森病患者睡眠质量,但帕病1号方疗效优于美多芭组。
结论：
帕病1号方治疗强直少动型早期帕金森病在改善运动症状上疗效与美多芭相仿,在改善生活质量、中医症候、睡眠质量上则优于美多芭组。
第二部分帕病1号方对帕金森病模型大鼠多巴胺能神经元保护作用的研究
目的：
研究帕病1号方对PD模型大鼠黑质多巴胺能神经元的保护作用。
方法：
采用6-羟基多巴胺(6-OHDA)纹状体两点注射法造成左侧纹状体损毁模型大鼠,把造模成功的40只大鼠,完全随机法分为3组,同时设立正常对照组,高、低剂量组分别予以帕病1号方颗粒制剂按18g·kg-1,9g·kg-1给药,模型组、正常组每只大鼠均予以4m1等体积蒸馏水,以上各组均每天给药1次,持续给药32天后,进行大鼠行为学测试,观察阿朴吗啡诱导的行为学改变,HE染色观察多巴胺能神经元的病理形态学变化。
结果：
1.神经行为学方面,治疗后,与同期模型组相比,高、低剂量组PD模型大鼠的旋转行为学明显改善(P<0.01)；且高、低剂量组对旋转行为的改善存在量效关系(P<0.01)。
2.组织形态学结果,空白对照组黑质区组织细胞正常。模型组大鼠元有明显损伤,表现为黑质区神经元数量减少,部分发生固缩,胶质细胞浸润,而帕病1号方高、低剂量组黑质内也存在神经元减少的现象,但程度明显较轻。说明帕病1号方可对抗6-OHDA所致的神经元损伤。
结论：
帕病1号方对帕金森病大鼠模型黑质多巴胺能神经元有保护作用,能抑制神经细胞的凋亡。
第三部分帕病1号方对帕金森病大鼠模型纹状体SOD的活性、GSH、MDA的含量的影响
目的：
观察帕病1号方对帕金森病模型大鼠氧化应激的影响。
方法：
模型制作、分组及治疗同第二部分,考虑本化学实验三个指标,需要纹状体组织较多,各组随机分为两部分；麻醉状态下迅速取毁损侧纹状体,用冰生理盐水制成10%的组织匀浆,取上清液,用比色法测定PD大鼠左侧纹状体匀浆中超氧化物歧化酶(SOD)的活性及谷胱甘肽(GSH)、丙二醛(MDA)的含量。
结果：
氧化应激方面,与模型组相比,高剂量组可显著提高SOD活性(P<0.01)和GSH含量(P<0.01),降低了MDA含量(P<0.01)；低剂量组SOD无显著改变(P>0.05),但提高了GSH含量(P<0.01)、降低了MDA含量(P<0.01)；与低剂量相比,高剂量组SOD活性无显著改变(P>0.05),但提高了GSH含量(P<0.01)、降低了MDA含量(P<0.01)。
结论：
帕病1号方颗粒能提高PD模型大鼠抗氧化能力和清除自由基的能力,且抗氧化作用呈一定的量效关系。
第四部分基于AKT信号通路探讨帕病1号颗粒的神经保护作用
目的：
探讨帕病1号方颗粒对帕金森病(PD)模型大鼠发挥神经保护作用的机制。
方法：
模型制作、分组及治疗同第三部分,进行中脑黑质石蜡切片免疫组化实验。
结果：
免疫组化方面,与模型组相比,高、低剂量组P-Akt(ser473)、Bcl-2、Bax阳性细胞数及Bcl-2/Bax比值存在显著差异(P<0.01或P<0.05),且高、低剂量组上述指标相比存在量效关系(P<0.01或P<0.05)。
结论：
说明帕病1号方对Akt信号转导通路有影响作用,可能具有神经营养作用,且存在一定量效关系,而P-Akt、Bcl-2和Bax可能是该途径上起主要作用的靶点。
Parkinson's disease (PD) is a common degenerative disease of the cen tral nervous system, its etiology and pathogenesis is still unknown. Levo dopa has been the mainstay therapy of Parkinson's disease (PD), however i t has obvious side-effects and complications in long-term treatment. Ther efore, people pay close attention to the the Chinese medicine therapy. Pa bing I Formula which is the experiential prescription of professor Luo X iaodong, To objectively evaluate the clinical efficacy of Chinese medici ne Pabing I Formula, we observe the motor signs, quality of life inclding, TCM symptoms, quality of sleep in early-stage PD patients in two-month t reatment. In order to explore the pharmacodynamic of Pabing Ⅰ Formula, PD rats were induced by injection of6-hydroxy dopamine(6-OHDA) twice stereo taxically into the left side of striatum, pathomorphology, biochemical,dete ction and immunohistochemical staining are proformed in order to probe in to the therapeutic effect of Pabing I Formula, and identify its mechanis m of antioxidation and through Akt signaling pathway to play neuroprotec tive effect. The study is divided into four parts as follows:
Part one Clinical experiment study of Pabing I Formula granule for early stage Parkinson's Disease of stiffness and less dynamic Pattern
Object ive
To observe the effect of Pabing Ⅰ Formula granule for early stage Park inson's disease of stiffness and less dynamic pattern
Methods
55cases of early stage parkinson's disease patients were randomly di vided into two groups, the treatment group (N=27) received therapy of Pab ing I Formula granule, the control group (N=28) received therapy of madopa r. After2months treatment, Efficacy was evaluated with the unified park inson disease rating scale (UPDRS)III(motor function section), Parkinson' s Disease Questionnaire (PDQ-39),TCM symptoms of Parkinson's disease, Par kinson disease sleep scale (PDSS). the blood pressure, pulse rate, blood and urine routine, liver and renal functions, electrocardiogram(ECG) and adverse reactions were monitored as the indices for safety supervise.
Results
1. In improving motor signs:After treatment, there were7patients (25.93%)in Pabing I Formula treatment group markedly improved and17patie nts(62.96%) improved, the total effective rate was88.89%; while in madopa r group, the corresponding outcomes were8(28.57%) and16(57.14%), respec tively, the total effective rate was85.71%; showing insignificant differ ence between the two groups (P>0.05). As far as motor signs were concern ed, Parameters such as UPDRSIII scores was significantly decreased in Pabi ng I Formula and madopar group after treatment (P<0.01). It showed no stat istical significant difference between groups(P>0.05), So, Pabing I Formula granule group in improving the Motor function of the efficacys was simil ar to the madopar group
2. the quality of life of the efficacys:After treatment, there were8patients (29.63%)in Pabing I Formula treatment groupmarkedly improvedb a nd15patients(55.56%) improved, the total effective rate was85.19%; whil e in madopar group, the corresponding outcomes were4(14.29%) and13(46.43%), respectively, the total effective rate was60.71%; showing significa nt difference between the two groups(P<0.05). The quality of life of the efficacys score was significantly decreased in Pabing I Formula and madopa r groupafter treatment(P<0.01). It showed statistical significant differ ence between groups (P<0.05). So, Pabing I Formula granule groupin improvi ng the quality of life of the efficacys was superior to the madopar grou p.
3. changes of TCM symptoms:After treatment, there were7patients (25.93%)in Pabing I Formula treatment group markedly improved and16patients (59.26%) improvedb, the total effective rate was85.19%; while in madopar group, the corresponding outcomes were2(13.33%) and15(46.67%), respecti vely, the total effective rate was60.71%; showing significant difference between the two groups (P<0.05). The changes of TCM symptoms was signifi cantly decreased in Pabing I Formula and madopar group after treatment(P<0.01). It showed statistical significant difference between groups (P<0.01), So, Pabing I Formula granule groupin improving the TCM symptoms was su perior to the madopar group.
4. changes of PDSS scores Thechanges of PDSS scores was significantly decreased in Pabing I Formula and madopar groupafter treatment(P<0.01). I t showed statistical significant difference between groups (P<0.05), So, P abing I Formula granule group in improving the PDSS scores was superior t o the madopar group. Conelusion
Pabing I Formula granule group in improving the Motor function of the efficacy was similar to the madopar group, but was superior to madopar gr oupin improving the quality of life of the efficacy TCM symptoms and PDSS scores.
Part two Involvement in Neuroprotective Effect of Pabing I Formula on the Dopaminergic Neurons of Parkinson's disease Rats
Object ive
To explore neuroprotective effect of Pabing Ⅰ Formula on the nigrostr iatal dopaminergic neurons of Parkinson's disease rats.
Methods
PD rats were induced by injection of6-hydroxy dopamine(6-OHDA) twice stereotaxically into the left side of striatum, the40PD rats were rand omly divided into three groups, at the same time, the normal groupwas esta blished; the high dose group and low dose groupreceived therapy of Pabin g I Formula granule(18g·kg-1,9g· kg-1), The model groupand normal groupwere given4ml distilled water at the same volume for every rat. Four groups were all given treatment once a day, the treatment lasted for32days to execute behavioral studies, HE staining was used to observe the pathomorp hological changes of SNc.
Results
1. In rotational behavior, after treatment, The high dose group、low dos e group compared with the model group at the same stage had significant d ifferences (P<0.01); and there was a significant difference between the high dose groupand the low dose group (P<0.01)
2. Histomorphological observation showed the neurons in SNc zone of m odel rats were obviously damaged, which were manifested by severely deer ease of neurons, condensed cellular nucleus and Partly infiltrated glial celis. The high dose group、low dose group administration can partly rever se the changes. It means that Parbin I Formula granule protected neurons against the neurotoxicity of6-OHDA.
Conelusion
The Present study demonstrated that Parbin I Formula granule treatmen t showed its neuroprotective effects.
Part three The Influence of Pabing I Formula on Contents of SOD、GSH and MDA in Striatum
Objective
To study effect of Parbin I Formula on the oxidation stress response of Parkinson's disease rats.
Methods
Parkinson's disease rats probable, dividing into groups and medication intervention, all the three steps were the same as the second part, the c olorimetric assays were used to detect the activities of superoxidase dis mutase (SOD)、the levels of glutathione (GSH) and malonaldehyde (MDA) with tissue homogenate that came from the left side of striatum.
ResuIts
compared with the model group, the activities of SOD (P<0.01)and the content of GSH (P<0.01) were obviously increased and the content of MDA (P <0.01) was obviously reduced in high dose group, there was no significant difference in the low dose group of the activities of SOD (P>0.05), but, the content of GSH (P<0.01) was obviously increased and the content of MD A (P<0.01) was obviously reduced in low dose group; and compared with the low group, there was no significant difference in the high dose group of the activities of SOD (P>0.05), but the content of GSH (P<0.01) were ob viously increased and the content of MDA (P<0.01) was obviously reduced i n high dose group.
Conelusion
Parbing Ⅰ formula granuleprobable through enhance antioxidation abilit y and eliminate free radicals, the neuroprotective role exists dose-effec t relationship.
Part four Neuroprotective mechanism of Pabing I Formula granule in Parkins on's Disease Rats probable trough Akt signaling Pathway
Objective
To discuss the probable neuroprotective mechanism of Pabing Ⅰ Formulag ranule in Parkinson's Disease rats.
Methods
Parkinson's disease rats producing, dividing into groups and medicat ion intervention, all the four steps were the same as the third part, the immunohistochemistry experiments also to be executed.
Results
The high dose group、low dose group compared with the model group had significant differences (P<0.01或P<0.05) in the number of positive P-Akt (ser473)、positive Bcl-2、positive Bax cells and in the Bcl-2/Bad ratio, there were significant differences between the high dose group and the1ow dose group (P<0.01或P<0.05) in the above indicators.
Conclusion
Parbing Ⅰ formula granule probable through Akt signaling pathway to p1ay neuroprotective effect.the neuroprotective role exists dose-effect r elationship.
第一部分帕病1号方对强直少动型早期帕金森病的临床观察
目的：
观察帕病1号方对强直少动型早期帕金森病的临床疗效。
方法：
将55例早期帕金森病患者随机分为2组,治疗组27例予帕病1号方治疗,对照组28例予美多芭治疗,疗程均为2个月；疗程结束后进行疗效评价,疗效评价指标为帕金森病量表(UPDRS)第三部分(运动功能)、帕金森病生存质量量表(PDQ-39)、帕金森病中医证候积分量表、睡眠量表(PDSS)评分相对于基线的变化,同时观察血压、脉搏、血尿常规、肝肾功能、心电图及不良反应等。
结果：
1.在改善运动功能方面,帕病1号方组27例患者,显效25.93%(7/27),有效62.96%(17/27),总有效率88.89%；美多巴组28例患者,显效28.57%(8/28),有效57.14%(16/28),总有效率85.71%,两组显效有效率比较差异无统计学意义(P>0.05)。帕病1号方组、美多芭组的UPDRSⅢ积分治疗前后比较均有显著性差异(P<0.01)；两组组间比较无差异性(P>0.05)。提示在改善早期PD患者运动功能方面,中药复方帕病1号方与美多巴疗效相当。
2.在改善生活质量方面,帕病1号方组27例患者,显效29.63%(8/27),有效55.56%(15/27),总有效率85.19%；美多巴组28例患者,显效14.29%(4/28),有效46.43%(13/28),总有效率60.71%,两组显效有效率比较差异有统计学意义(P<0.05)；帕病1号方组、美多芭组两组治疗前后生活质量积分比较均有显著性差异(P<0.01)；两组组间比较亦存在显著性差异(P<0.05),说明帕病1号方和美多芭均可改善早期帕金森病患者生活质量,但帕病1号方疗效优于美多芭组。
3.在改善中医症候方面,帕病1号方组27例患者,显效25.93%(7/27),有效59.26%(16/27),总有效率85.19%；美多巴组28例患者,显效13.33%(2/28),有效46.67%(15/28),总有效率60.71%,两组显效有效率比较差异有统计学意义(P<0.05)；帕病1号方组、美多芭组两组治疗前后中医症候积分比较均有显著性差异(P<0.01)；两组组间比较亦存在显著性差异(P<0.01)。说明帕病1号方和美多芭均可改善早期帕金森病患者中医症候,但帕病1号方疗效优于美多芭组。
4.在改善睡眠质量方面,帕病1号方组、美多芭组两组治疗前后睡眠质量积分比较均有显著性差异(P<0.01)；两组组间比较亦存在显著性差异(P<0.05)。说明帕病1号方和美多芭均可改善早期帕金森病患者睡眠质量,但帕病1号方疗效优于美多芭组。
结论：
帕病1号方治疗强直少动型早期帕金森病在改善运动症状上疗效与美多芭相仿,在改善生活质量、中医症候、睡眠质量上则优于美多芭组。
第二部分帕病1号方对帕金森病模型大鼠多巴胺能神经元保护作用的研究
目的：
研究帕病1号方对PD模型大鼠黑质多巴胺能神经元的保护作用。
方法：
采用6-羟基多巴胺(6-OHDA)纹状体两点注射法造成左侧纹状体损毁模型大鼠,把造模成功的40只大鼠,完全随机法分为3组,同时设立正常对照组,高、低剂量组分别予以帕病1号方颗粒制剂按18g·kg-1,9g·kg-1给药,模型组、正常组每只大鼠均予以4m1等体积蒸馏水,以上各组均每天给药1次,持续给药32天后,进行大鼠行为学测试,观察阿朴吗啡诱导的行为学改变,HE染色观察多巴胺能神经元的病理形态学变化。
结果：
1.神经行为学方面,治疗后,与同期模型组相比,高、低剂量组PD模型大鼠的旋转行为学明显改善(P<0.01)；且高、低剂量组对旋转行为的改善存在量效关系(P<0.01)。
2.组织形态学结果,空白对照组黑质区组织细胞正常。模型组大鼠元有明显损伤,表现为黑质区神经元数量减少,部分发生固缩,胶质细胞浸润,而帕病1号方高、低剂量组黑质内也存在神经元减少的现象,但程度明显较轻。说明帕病1号方可对抗6-OHDA所致的神经元损伤。
结论：
帕病1号方对帕金森病大鼠模型黑质多巴胺能神经元有保护作用,能抑制神经细胞的凋亡。
第三部分帕病1号方对帕金森病大鼠模型纹状体SOD的活性、GSH、MDA的含量的影响
目的：
观察帕病1号方对帕金森病模型大鼠氧化应激的影响。
方法：
模型制作、分组及治疗同第二部分,考虑本化学实验三个指标,需要纹状体组织较多,各组随机分为两部分；麻醉状态下迅速取毁损侧纹状体,用冰生理盐水制成10%的组织匀浆,取上清液,用比色法测定PD大鼠左侧纹状体匀浆中超氧化物歧化酶(SOD)的活性及谷胱甘肽(GSH)、丙二醛(MDA)的含量。
结果：
氧化应激方面,与模型组相比,高剂量组可显著提高SOD活性(P<0.01)和GSH含量(P<0.01),降低了MDA含量(P<0.01)；低剂量组SOD无显著改变(P>0.05),但提高了GSH含量(P<0.01)、降低了MDA含量(P<0.01)；与低剂量相比,高剂量组SOD活性无显著改变(P>0.05),但提高了GSH含量(P<0.01)、降低了MDA含量(P<0.01)。
结论：
帕病1号方颗粒能提高PD模型大鼠抗氧化能力和清除自由基的能力,且抗氧化作用呈一定的量效关系。
第四部分基于AKT信号通路探讨帕病1号颗粒的神经保护作用
目的：
探讨帕病1号方颗粒对帕金森病(PD)模型大鼠发挥神经保护作用的机制。
方法：
模型制作、分组及治疗同第三部分,进行中脑黑质石蜡切片免疫组化实验。
结果：
免疫组化方面,与模型组相比,高、低剂量组P-Akt(ser473)、Bcl-2、Bax阳性细胞数及Bcl-2/Bax比值存在显著差异(P<0.01或P<0.05),且高、低剂量组上述指标相比存在量效关系(P<0.01或P<0.05)。
结论：
说明帕病1号方对Akt信号转导通路有影响作用,可能具有神经营养作用,且存在一定量效关系,而P-Akt、Bcl-2和Bax可能是该途径上起主要作用的靶点。
Parkinson's disease (PD) is a common degenerative disease of the cen tral nervous system, its etiology and pathogenesis is still unknown. Levo dopa has been the mainstay therapy of Parkinson's disease (PD), however i t has obvious side-effects and complications in long-term treatment. Ther efore, people pay close attention to the the Chinese medicine therapy. Pa bing I Formula which is the experiential prescription of professor Luo X iaodong, To objectively evaluate the clinical efficacy of Chinese medici ne Pabing I Formula, we observe the motor signs, quality of life inclding, TCM symptoms, quality of sleep in early-stage PD patients in two-month t reatment. In order to explore the pharmacodynamic of Pabing Ⅰ Formula, PD rats were induced by injection of6-hydroxy dopamine(6-OHDA) twice stereo taxically into the left side of striatum, pathomorphology, biochemical,dete ction and immunohistochemical staining are proformed in order to probe in to the therapeutic effect of Pabing I Formula, and identify its mechanis m of antioxidation and through Akt signaling pathway to play neuroprotec tive effect. The study is divided into four parts as follows:
Part one Clinical experiment study of Pabing I Formula granule for early stage Parkinson's Disease of stiffness and less dynamic Pattern
Object ive
To observe the effect of Pabing Ⅰ Formula granule for early stage Park inson's disease of stiffness and less dynamic pattern
Methods
55cases of early stage parkinson's disease patients were randomly di vided into two groups, the treatment group (N=27) received therapy of Pab ing I Formula granule, the control group (N=28) received therapy of madopa r. After2months treatment, Efficacy was evaluated with the unified park inson disease rating scale (UPDRS)III(motor function section), Parkinson' s Disease Questionnaire (PDQ-39),TCM symptoms of Parkinson's disease, Par kinson disease sleep scale (PDSS). the blood pressure, pulse rate, blood and urine routine, liver and renal functions, electrocardiogram(ECG) and adverse reactions were monitored as the indices for safety supervise.
Results
1. In improving motor signs:After treatment, there were7patients (25.93%)in Pabing I Formula treatment group markedly improved and17patie nts(62.96%) improved, the total effective rate was88.89%; while in madopa r group, the corresponding outcomes were8(28.57%) and16(57.14%), respec tively, the total effective rate was85.71%; showing insignificant differ ence between the two groups (P>0.05). As far as motor signs were concern ed, Parameters such as UPDRSIII scores was significantly decreased in Pabi ng I Formula and madopar group after treatment (P<0.01). It showed no stat istical significant difference between groups(P>0.05), So, Pabing I Formula granule group in improving the Motor function of the efficacys was simil ar to the madopar group
2. the quality of life of the efficacys:After treatment, there were8patients (29.63%)in Pabing I Formula treatment groupmarkedly improvedb a nd15patients(55.56%) improved, the total effective rate was85.19%; whil e in madopar group, the corresponding outcomes were4(14.29%) and13(46.43%), respectively, the total effective rate was60.71%; showing significa nt difference between the two groups(P<0.05). The quality of life of the efficacys score was significantly decreased in Pabing I Formula and madopa r groupafter treatment(P<0.01). It showed statistical significant differ ence between groups (P<0.05). So, Pabing I Formula granule groupin improvi ng the quality of life of the efficacys was superior to the madopar grou p.
3. changes of TCM symptoms:After treatment, there were7patients (25.93%)in Pabing I Formula treatment group markedly improved and16patients (59.26%) improvedb, the total effective rate was85.19%; while in madopar group, the corresponding outcomes were2(13.33%) and15(46.67%), respecti vely, the total effective rate was60.71%; showing significant difference between the two groups (P<0.05). The changes of TCM symptoms was signifi cantly decreased in Pabing I Formula and madopar group after treatment(P<0.01). It showed statistical significant difference between groups (P<0.01), So, Pabing I Formula granule groupin improving the TCM symptoms was su perior to the madopar group.
4. changes of PDSS scores Thechanges of PDSS scores was significantly decreased in Pabing I Formula and madopar groupafter treatment(P<0.01). I t showed statistical significant difference between groups (P<0.05), So, P abing I Formula granule group in improving the PDSS scores was superior t o the madopar group. Conelusion
Pabing I Formula granule group in improving the Motor function of the efficacy was similar to the madopar group, but was superior to madopar gr oupin improving the quality of life of the efficacy TCM symptoms and PDSS scores.
Part two Involvement in Neuroprotective Effect of Pabing I Formula on the Dopaminergic Neurons of Parkinson's disease Rats
Object ive
To explore neuroprotective effect of Pabing Ⅰ Formula on the nigrostr iatal dopaminergic neurons of Parkinson's disease rats.
Methods
PD rats were induced by injection of6-hydroxy dopamine(6-OHDA) twice stereotaxically into the left side of striatum, the40PD rats were rand omly divided into three groups, at the same time, the normal groupwas esta blished; the high dose group and low dose groupreceived therapy of Pabin g I Formula granule(18g·kg-1,9g· kg-1), The model groupand normal groupwere given4ml distilled water at the same volume for every rat. Four groups were all given treatment once a day, the treatment lasted for32days to execute behavioral studies, HE staining was used to observe the pathomorp hological changes of SNc.
Results
1. In rotational behavior, after treatment, The high dose group、low dos e group compared with the model group at the same stage had significant d ifferences (P<0.01); and there was a significant difference between the high dose groupand the low dose group (P<0.01)
2. Histomorphological observation showed the neurons in SNc zone of m odel rats were obviously damaged, which were manifested by severely deer ease of neurons, condensed cellular nucleus and Partly infiltrated glial celis. The high dose group、low dose group administration can partly rever se the changes. It means that Parbin I Formula granule protected neurons against the neurotoxicity of6-OHDA.
Conelusion
The Present study demonstrated that Parbin I Formula granule treatmen t showed its neuroprotective effects.
Part three The Influence of Pabing I Formula on Contents of SOD、GSH and MDA in Striatum
Objective
To study effect of Parbin I Formula on the oxidation stress response of Parkinson's disease rats.
Methods
Parkinson's disease rats probable, dividing into groups and medication intervention, all the three steps were the same as the second part, the c olorimetric assays were used to detect the activities of superoxidase dis mutase (SOD)、the levels of glutathione (GSH) and malonaldehyde (MDA) with tissue homogenate that came from the left side of striatum.
ResuIts
compared with the model group, the activities of SOD (P<0.01)and the content of GSH (P<0.01) were obviously increased and the content of MDA (P <0.01) was obviously reduced in high dose group, there was no significant difference in the low dose group of the activities of SOD (P>0.05), but, the content of GSH (P<0.01) was obviously increased and the content of MD A (P<0.01) was obviously reduced in low dose group; and compared with the low group, there was no significant difference in the high dose group of the activities of SOD (P>0.05), but the content of GSH (P<0.01) were ob viously increased and the content of MDA (P<0.01) was obviously reduced i n high dose group.
Conelusion
Parbing Ⅰ formula granuleprobable through enhance antioxidation abilit y and eliminate free radicals, the neuroprotective role exists dose-effec t relationship.
Part four Neuroprotective mechanism of Pabing I Formula granule in Parkins on's Disease Rats probable trough Akt signaling Pathway
Objective
To discuss the probable neuroprotective mechanism of Pabing Ⅰ Formulag ranule in Parkinson's Disease rats.
Methods
Parkinson's disease rats producing, dividing into groups and medicat ion intervention, all the four steps were the same as the third part, the immunohistochemistry experiments also to be executed.
Results
The high dose group、low dose group compared with the model group had significant differences (P<0.01或P<0.05) in the number of positive P-Akt (ser473)、positive Bcl-2、positive Bax cells and in the Bcl-2/Bad ratio, there were significant differences between the high dose group and the1ow dose group (P<0.01或P<0.05) in the above indicators.
Conclusion
Parbing Ⅰ formula granule probable through Akt signaling pathway to p1ay neuroprotective effect.the neuroprotective role exists dose-effect r elationship.
引文
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