Aim To investigate the antinociception, tolerance and withdrawal abstinence of δ/μ/κ opioid receptor triple agonist KUST201 ( DPI-125 ) in rats. Methods Male Sprague-Dawley rats were used to de-termine the time course of analgesic effects and ED50 effects of co-administration of naltrindole were assessed as well. In withdrawal experiments, KUST201 was ad-ministrated twice daily for 3 d with increasing doses each day. On the 4th day, the rats were given a single dose, challenged with naloxone 3 h later, and signs of abstinence were monitored. Results The ED50 values of KUST201 were 0. 34 mg·kg-1 in tail-pinch test and 0. 68 mg · kg-1 in hot-plate test. The antinociception actions of KUST201 started to decrease 1 h after ad-ministration, and disappeared after 2 h. In chronic tol-erance experiments, the antinociception actions started to decrease on d 3 , and completely disappeared on d 7 . Naltrindole could reduce the antinociceptive action of KUST201. In withdrawal experiments, abstinence scores increased significantly in the dose range between 2~8 times of tail-pinch ED50 . Conclusion Compared with previously reported δ/μ/κ triple agonist DPI-3290 , KUST201 exhibits similar antinociceptive effects in rats. The chronic tolerance to KUST201 actions de-velops less quickly, but the abstinence scores of KUST201 are slightly higher. The activation of δ-opi-oid receptor can synergistically enhance the antinoci-ception mediated by μ-receptor.

OBJECTIVE: Studies revealed that cerebellar flocculus-paraflocculus complex plays an important in vestibular compensation. To observe the expression change of Group I mGluRs in flocculus following left unilateral labyrinthectomy (UL). METHOD: After setting left labyrinthectomy, the change of Group I mGluRs was detected by RT-PCR. RESULT: Group I mGluR5 was induced increase in both side flocculus after unilateral labyrinthectomy. By contrast, mGluR1 was induced decrease. However, that of the lesioned side was stronger than that of the unlesioned side. CONCLUSION UL can induce change of Group I mGluRs in the flocculus. The fall in the resting discharge of the primary vestibular afferents and/or in the deafferented central vestibular neurons may cause the change of mGluRs. But the significance of the change of mGluRs in the vestibular compensation is still unknown.
Animals ; Cerebellar Nuclei ; metabolism ; Male ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism ; Vestibular Nuclei ; metabolism ; Vestibule, Labyrinth ; metabolism

OBJECTIVE: To observe the expression of mGluR5 in the medial vestibular nucleus (MVN) following unilateral labyrinthectomy (UL). METHOD: Thirty Wistar rats were randomly divided into two groups. Twenty four animals received unilateral labyrinthectomy while the others maintained labyrinthine well. After setting left labyrinthine, the change of mGluR5 was induced by immunohistochemistry, in situ hybridization. RESULT: mGluR5 was increased in lesioned side MVN after unilateral labyrinthectomy. The 12 h post-UL was highest. Then it was decrease in 36 h post-UL, while 7 d post-UL was same as control group. The change of contralateral was same as that in ipsilateral. CONCLUSION UL can induce increase of mGluR5 in the MVN. The reduced resting discharge in the primary vestibular afferents or in the central vestibular neurons may be responsible for the change of mGluR5. However the significance of the change of mGluR1 in the vestibular compensation is still unknown.
Animals ; Male ; Postoperative Period ; Rats ; Rats, Wistar ; Receptor, Metabotropic Glutamate 5 ; Receptors, Metabotropic Glutamate ; metabolism ; Vestibular Nuclei ; metabolism ; Vestibule, Labyrinth ; metabolism ; surgery

OBJECTIVE: To further investigate the mechanisms of hair cell generation or regeneration, the primary culture systems of cochlear sensory epithelial cell (CSEC) of rats were established. METHOD: Cochlear sensory epithelial (containing the organ of Corti) of postnatal day 1 (P1) rats was isolated by mechanical dissociation. The explants were grown on sterilized disposable plastic dishes,cultured in Dulbecco modified Eagle medium(DMEM), and observed daily by inverted microscopy. The culture medium was changed twice a week. The pure CSEC was harvested by the limiting dilution method. CSEC was identified by immunocytochemical method with cytokeratin 18, vimentin, Brn3. a, Calretinin, BrdU and ultrastructural examination with transmission electron microscopy. The markers of epithelial cell and the markers of hair cell were used to identify the origin and character of CSEC. CSEC mitotic division was detected by BrdU staining of nuclear DNA. RESULT: The fresh explants were light yellow. The morphology of CSEC couldn't be seen clearly under the inverted microscope because of the complex structures of cochlear sensory epithelial. CSEC grew out of the explants usually at 2nd culture day. Fibroblast like cells (FLC) around the CSEC grew faster than CSEC, but could easily be excluded. Pure CSEC may grow into monolayer with 'cobblestone-like' appearance and show a large, flat, polygonal epithelial morphotype with big, round nuclei. Some cells showed 'Dome' formation, probably due to fluid collection underneath the cell monolayer. The culture CSEC coexpressed cytokeratin 18 and vimentin has rich microvilli and complex tight junction,which indicated the epithelial origination of CSEC. Coexpressed of the Brn3. a and Calretinin of the hair cell characteristic markers suggested the culture cell may represent rat progenitor hair cell. BrdU staining showed CSEC produced new hair cell-like cell (progenitor hair cell) by the mitotic division. CONCLUSION The primary culture systems of cochlear sensory epithelial cell of rats were successfully established in vitro. CSEC coexpressed the characteristic markers of the immature hair cell,which identified the culture cell may represent progenitor cell of rats hair cell. It may be a suitable model for in-depth investigation the molecular mechanisms of hair cell generation or regeneration.
Animals ; Cell Culture Techniques ; methods ; Cell Division ; Cells, Cultured ; Cochlea ; cytology ; Epithelial Cells ; cytology ; Hair Cells, Auditory ; cytology ; Rats ; Rats, Wistar

This paper　explored the disease mechanism of autism spectrum disorders （ASD） from the perspectives of “vital activity” and “qi configuration”， and it is believed that “vital activity” represents the internal regulatory mechanisms of the human body， while “qi configuration” represents the ability of the body to communicate and adapt to the external environment. Abnormal genetic factors lead to the extinction of vital activity in children with ASD， resulting in increased susceptibility to ASD. Environmental instability leads to the solitary qi configuration in ASD， triggering and exacerbating the manifestations of ASD on the basis of genetic susceptibility. In addition， epigenetic mechanisms also play an important role in the pathogenesis of ASD. Imbalances in vital activity and disruptions in qi configuration result in failure in qi transformation of zang-fu organs， with abnormal symptoms manifested through the five orifices. It is proposed that the treatment of ASD should aim to achieve a harmonious interaction between “vital activity” and “qi configuration” to accelerate the recovery of affected children.

Objective To explore the effect of the combination of Tuina and treadmill training on denervation skeletal muscle atrophy. Methods A total of 80 Sprague-Dawley rats (one month old) were randomly divided into control group (n=40) and manipulation group (n=40). Their sciatic nerves were transected, and the manipulative group accepted treadmill training and kneading of Tuina, while the control group accepted no intervention. Their muscle wet weight ratio, muscle satellite cells and insulin-like growth factor I (IGF-I) positive cells count were measured, and HE staining of gastrocnemius muscle were observed one, two, three and four months after intervention, ten rats in each group. Results Compared with the control group, the muscle wet weight ratio decreased three months after intervention (F=4.590, P<0.05), muscle satellite cells increased three months after intervention (F=12.466, P<0.01), and IGF-I positive cells increased two, three and four months after intervention (F>6.489, P<0.05). HE staining showed the skeletal muscle injury relieved somehow.Conclusion The combination of Tuina and treadmill training can relieve denervation skeletal muscle injury, but it is not enough for skeletal muscle atrophy, which may associate with promoting the expression of muscle satellite cells and IGF-I.