Therapic Effect And Mechanism Of Invigorating Kidney And Promoting Blood Flow Drugs In Parkinson's Disease

ObjectiveParkinson's disease (PD) is one of the refractory diseases. Its etiology is still unknown. Studies indicated that environmental, genetical and aging factor are involved in the pathogenesis of PD. Rapid progression have been acquired in therapy of PD by using traditional Chinese medicine in recent years, but the underlying mechanism is still unclear. This study aimed to evaluate the therapeutic effect of traditional Chinese medicine "Bushen Huoxue Yin" on PD and to elucidate the possible mechanism of it through observing the change of morphology and molecular biology by using immunohistochemistry, reverse transcription-polymerase chain reaction (RT-PCR) and position emission tomography (PET). The results of this study will shed light on the treatment of PD.Methods110 Sprague-Dawley (SD) rats were devided into 2 groups at random :control group (20 rats)and mockup group(90 rats).The PD rat model was achieved by injecting 6-OHDA into the right striatum. 53 rats that showed PD were further divided into 2 groups: traditional Chinese medicine group(27) and model group(26). The rats in traditional Chinese medicine group were treated with Bushen Huoxue Yin by gavage for 8 weeks and the other groups were treated with physiological saline.Observe the change of rotation behavior induced by apomorphine after therapy.We selected 10 rats randomly from each group to evaluate the effect of Bushen Huoxue Yin on the number of tyrosine hydroxylase (TH) positive neurons cell in substantia nigra compacta(SNc).One rat from each group was injected ¹¹C-β-CFT as radiotracer from tail vein and the images were acquired by PET imaging before and after therapy.The remaining 9 rats in control group, 16 rats in treated grouop and 15 rats in model group were decollated and obtained brains to detect the relative mRNA expression of nuclear receptor-related factor 1 (Nurr1) and muscarinic acetylcholine receptor 5(M5) byusing RT-PCR, which was the consequence of those comparing with reference geneβ-actin mRNA expression.All results were analyzed by using CHISS Statistical Software.Results1. Bushen Huoxue Yin improved the rotational behavior of PD rats markedly andreduced the number of rotation obviously when compared with the model group(P<0.01).TH immunohistochemistry results show that the number of TH positive neurons cell of SNc in lesion side were reduced obviously in model group and which were increased significantly in treat group(P<0.01).The cell's volume was more bigger than before in treat group.2.¹¹C-β-CFT PET imaging showed that the DAT in lesioned side was decreased in all PDmodel rats' brains and the distribution was dissymmetry in uninjured side and injured side. Bushen Huoxue Yin could significantly increase DAT in lesioned side and the distribution was similar to uninjured side. But there was not obviously change in model group.3. RT-PCR results showed that the relative magnitude of Nurr1 mRNA and M5 mRNAexpression was decreased in model group than in treat group and control group(P<0.01).There was no disparation in treat group and control group(P>0.05).Conclusions1. The model of PD caused by 6-OHDA has lots of advantage such as high achievement ratio ,stability and reliability.2. Bushen Huoxue Yin can improve rotation behavior of PD rat.3. Bushen Huoxue Yin can increase content of DA by promoting DAT release, improving Nurr1 and M5 mRNA expression and raising content of TH. Those changes may be the possible mechanism of Bushen Huoxue Yin in the treatment of Parkinson's disease.