ABSTRACT
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.
ABSTRACT
Aim To evaluate the role of fisson I (Fisl) in methamphetamine (METH)-induced injur)' of human neuroblastoma (SH-SY5Y) cells cultured in vitro. Methods SH-SY5Y cells cultured in vitro were divided into different groups by the group design method∗. unsilent groups, silent negative groups and silent groups. Different concentrations of METH induced SH-SY5 Y cells in each group for 24 hours. The expression level of Fisl was detected by Western blot. The effect of METH on the proliferative capacity of SH-SY5Y cells was analyzed by CCK-8 cytotoxicity proliferation assay. The MMP level of METH on SH-SY5Y cells was detected by mitochondrial membrane potential detection kit (JC-1). The effect of METH on the mitochondrial ultrastructure of SH-SY5Y cells was observed by transmission electron microscopy. Results In unsilent group, silent negative group and silent group, the expression level of Fisl increased (P < 0. 05) and the proliferative capacity decreased (P < 0. 05) , and the MMP levels decreased (P <0. 05) with the increase of the concentration of SH-SY5Y cells induced by METH. Compared with the same concentration in unsi-lent group and silent negative group, in silent group, the expression level of Fisl in SH-SY5Y cells de-creased (P < 0. 05) , the proliferative capacity increased (P<0. 05) , and the MMP level increased (P < 0. 05). Compared with control group, 2. 0 mmol • L"1 METH induced unsilent groups, silent negative groups and silent groups, and transmission electron microscopy showed the increase in the mitochondrial small globular structure (P < 0. 01). Conclusion Fisl may play a key role in METH-induced injury of SH-SY5Y cells cultured in vitro.