RESUMO
ObjectiveTo investigate the effect of modified Xiaoyaosan on central dopamine transporter （DAT）/protein kinase C （PKC）-dependent signaling pathway in hyperprolactinemia （HPRL） rats. MethodHPRL rat model was established by chronic combined stress combined with intraperitoneal injection of metoclopramide. Ninety-six rats were randomly divided into six groups， namely， the blank group， model group， western medicine （bromocriptine， 0.001 g·kg-1·d-1） group， and high-， medium-， and low-dose （60， 30， 15 g·kg-1·d-1） modified Xiaoyaosan groups. After 14 days of administration， the serum prolactin （PRL） content was detected by enzyme-linked immunosorbent assay， the expression of tyrosine hydroxylase （TH） in rat hypothalamus by immunohistochemistry， and the protein expression of DAT and PKC in hypothalamus by Western blot. ResultCompared with the blank group， the model group exhibited significantly increased PRL and DAT （P<0.01）， but decreased TH and PKC （P<0.01）. Compared with the model group， bromocriptine and modified Xiaoyaosan at the medium dose significantly lowered the content of PRL （P<0.01）. The modified Xiaoyaosan at the medium and high doses elevated the expression of TH （P<0.05， P<0.01）. The expression levels of PKC in the medium- and low-dose modified Xiaoyaosan groups and the western medicine group were significantly increased （P<0.01）， while the DAT expression levels in the high-， medium-， and low-dose modified Xiaoyaosan groups and the western medicine group were decreased （P<0.01）. ConclusionThe modified Xiaoyaosan is able to up-regulate the expression of TH and down-regulate the level of DAT through PKC-dependent signaling pathway， thereby regulating the PRL.
RESUMO
Objective To evaluate the therapeutic effects of methamphetamine (MA) dependence and the repairment of DA neuronal function by SPECT corpus striatum DAT visual digital neural molecular imaging techniques.Methods 25 MA dependent patients (BPRS score ≥ 35) were treated by self-designed treatment program for more than 6 months.The clinical therapeutic effects were scored with reducing rate of BPRS.MA dependent patients were examined by SPECT corpus striatum DAT imaging before and after treatment,while healthy volunteers were examined only once.The SPECT corpus striatum DAT images were analyzed visually and quantitatively.Results The reducing rate of BPRS showed that the total effective rate was 80.0％.Visual analysis of SPECT corpus striatum DAT images showed that the distribution of DAT in the corpus striatum was regionally reduced or defected in various degrees before treatment,and was significantly increased after treatment.Quantitative analysis showed that the bilateral striatal V ((19.26 ± 2.85) cm3),m((20.22±2.99) g) and Ra(4.78±0.79) ％) of MA dependent patients were significantly lower compared with those of the healthy volunteers(respectively (35.39±4.42) cm3,(37.16±4.64) g and (7.93± 0.86) ％) (all P＜ 0.01) before treatment and were significantly improved (P＜ 0.01) after treatment (V:(22.80±4.28) cm3,m:(23.93± 4.49) g and Ra:(5.64 ± 0.99) ％) with a 76.0％ corpus striatum DAT improvement rate.However,the bilateral striatal V,m and Ra of MA dependent patients after treatment were still lower than those of the healthy volunteers (P＜0.01).There was no significant difference between the striatal DAT improvement rate and the BPRS reduction rate (P＞ 0.05).Conclusion SPECT corpus striatum DAT visual digital neural molecular imaging techniques are reliable in the evaluation of the treatment programs for MA dependence and the repair of DA neuronal function.
RESUMO
@#Cocaine is one of the main addiction drugs in the world. Scientists are always trying to discover why the addiction happens and find the methods to cure the cocaine addiction. The classics mechanism is that the cocaine binds with the dopamine transporter (DAT), then the retake of dopamine was blocked, and this resulted in the sustained excitement of the dopaminergic neuron. Now, it is found that the cocaine influence some systems relate to the gene expression of the "reward" circuit. This influence finally leads to the change of neuron dendritic plastisity in that area. All the changes are sustaining and these may be the foundation of some behavior effects about the cocaine addiction. At present, the main therapy orientation is decrease the contact between the cocaine and the neuron by idiosyncratic antibody, vaccine or enzyme. Here, related mechanism and therapies were mainly reviewed.
RESUMO
OBJECTIVE: Dopamine plays a key role in the proliferation regulation of the smooth muscle cells. The purpose of this study was to observe the degree of expression of dopamine D1 and D2 receptors and dopamine transporter (DAT) and to evaluate the influence of methylation about control of expression of DAT in uterine leiomyoma and normal myometrial tissue. METHODS: In 20 patients who underwent hysterectomy due to uterine leiomyoma, normal myometrial and leiomyoma specimens were obtained. The expression of dopamine D1 and D2 receptors and DAT was demonstrated by using RT-PCR and immunohistochemistry in each normal myometrium and leiomyoma. Analysis of the DNA methylation status of DAT was conducted using HpaII digestion and the methylation-sensitive PCR. RESULTS: The mRNA level of dopamine D1 receptor was relatively higher in normal myometrium than D2 receptor and it was also unchanged in leiomyomas. However, the mRNA levels of dopamine D2 receptor and DAT in leiomyomas were much higher than normal myometrium. Consistent with elevated mRNA levels, high levels of dopamine receptors protein expression were detected by immunohistochemistry in leiomyomas. The degree of methylation at CpG sites of the area intron 1 of DAT (genomic position, +377 - +888) was decreased in leiomyomas. CONCLUSION: These results suggest that overexpressed dopamine D2 receptor and DAT would be associated with proliferation of human uterine leiomyomas and the methylation status of the CpG island of DAT determines its expression.