| 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 PatternObject iveTo observe the effect of Pabing Ⅰ Formula granule for early stage Park inson’s disease of stiffness and less dynamic patternMethods55cases 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.Results1. 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 group2. 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. ConelusionPabing 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 RatsObject iveTo explore neuroprotective effect of Pabing Ⅰ Formula on the nigrostr iatal dopaminergic neurons of Parkinson’s disease rats.MethodsPD 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.Results1. 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.ConelusionThe 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 StriatumObjectiveTo study effect of Parbin I Formula on the oxidation stress response of Parkinson’s disease rats.MethodsParkinson’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.ResuItscompared 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.ConelusionParbing 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 PathwayObjectiveTo discuss the probable neuroprotective mechanism of Pabing Ⅰ Formulag ranule in Parkinson’s Disease rats.MethodsParkinson’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.ResultsThe 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.ConclusionParbing Ⅰ formula granule probable through Akt signaling pathway to p1ay neuroprotective effect.the neuroprotective role exists dose-effect r elationship. |
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