Abstract:
OBJECTIVE To study the regulatory effect of Changpu Yujin Decoction on the SNARE protein complex in the synaptosomes of Tourette syndrome (TS) model rats, and to reveal the pharmacodynamic mechanism of Changpu Yujin Decoction in the treatment of TS.
METHODS 240 SPF SD male rats (3 weeks) were randomly divided into blank group (
n=60) and model group (
n=180). Model group received intraperitoneal injection of 3, 3'-iminodipropionitrile to establish TS model. After the TS model was successfully established, the model rats were randomly divided into model group, tiapride group, and Changpu Yujin Decoction group, each with 60 rats. The intragastric administration was started from the next day after the TS model was made (d0). The blank group and the model group were given normal saline, and the other groups were given corresponding drugs, once a day, for 4 consecutive weeks. At d0, d7, d14, d21 and d28, 12 rats were randomly selected from each group. After anesthesia, the striatum was taken out, and the synaptosomes in the striatum were prepared by Percoll density gradient centrifugation. Morphological identification was performed under transmission electron microscope; The level of dopamine (DA) in the striatum was examined by ELISA; Expression of SNAP-25, Syntaxin-1a and VAMP-2 in the synaptosomes/striatumwere measured by qPCR, Western blot analysis and immunohistochemical staining.
RESULTS Compared with the blank group, the DA content in the striatum in the model group was reduced (
P < 0.01), and the expressions of SNAP-25, Syntaxin-1a, VAMP-2 mRNA and protein in the synaptosome/striatum significantly reduced (
P < 0.05,
P < 0.01); Compared with the model group, the DA content in striatum and the mRNA and protein expression levels of SNAP-25, Syntaxin-1a, VAMP-2 in the tiapride group and Changpu Yujin group showed a gradual increase trend during the intervention period (d7, d14, d21, d28); At d28 (after the end of treatment), the expressions of SNAP-25, Syntaxin-1a, VAMP-2 mRNA, Syntaxin-1a protein in synaptosome and SNAP-25 and VAMP-2 protein in the striatum were higher than those of tiapride group (
P<0.05,
P < 0.01).
CONCLUSION Changpu Yujin Decoction promotes the release of DA by regulating the expression of SNAP-25, Syntaxin-1a, and VAMP-2, thereby exerting its anti-tic effect.