Original Article The effects and mechanism of substance P2 in sedative and hypnotic of isoflurane mice

Na Wang, Haowei Wang, Ye Lu, Hongbin Yuan, Haijing Sun, Ruihua Ji, Wenyun Xu
2017 Int J Clin Exp Med   unpublished
Objective: To investigate the changes of serum substance P (Substance P, SP) content and its effects on sedation and hypnosis after mice inhale Isoflurane. Methods: 45 mice were randomly divided into Isoflurane (Isoflurane, Iso) group, Dexmedetomidine (Dexmedetomidine, Dex) group and Isoflurane combined with substance P receptor antagonist agent (Antagonist of Substance P, Iso+A-SP) group; using ELISA method to detect serum substance P content of groups of mice, applying analepsia experiment to
more » ... epsia experiment to record sleep time of groups of mice, applying Hot-plate and writhing test to record threshold of pain in Hot-plate method and writhing frequency of groups of mice. Brain stereotaxic, nucleus spile, micro-injection and polysomnography were used to apply in the blank control group (PBS), substance P group (SP group), substance P receptor antagonist agent group (A-SP group), 3-Mercaptopropionic acid group (3-MP group) and substance P+3-Mercaptopropionic acid group (SP+3-MP group) for observing the mechanism of action of SP on sleep of mice. Results: Iso group had the strongest sedation and the Iso+A-SP group was the weakest. For writhing frequency, Dex group and Iso+A-SP group were significantly more than that of the Iso group, while Iso+A-SP group was more than that of the Dex group; after medication, the threshold of pain in Iso+A-SP group had no significant difference compared with medication before, while Iso group and Dex group were prolonged pain threshold; Iso group and Dex group pain threshold were the longest when the medication for 10 minutes, the above difference was statistically significant (P<0.05); the sleep time of Iso group was longer than that of Iso+A-SP group and Dex group, the sleep time of Iso+A-SP group was the shortest, and there was statistical difference (P<0.05); before medication, there was no significant difference in the concentration of substance P in each group; after medication, Iso group and Iso+A-SP group of P substance concentration difference was quite little, but Iso group and Iso+A-SP group were significantly higher than the Dex group, the difference was statistically significant (P<0.05). Compared with the control group (PBS group), sleep time of micro-injection SP (SP group) in the ventrolateral preoptic area (vLPO) in mice was significantly increased while the awakening time was significantly decreased; compared with the control group (PBS group), sleep time of micro-injection ASP (A-SP group) in vLPO was significantly decreased while the awakening time was significantly increased; compared with the 3-MP group, in the vLPO micro-injection of gamma aminobutyric acid (GABA) compounded key enzyme inhibitors substance P+3-Mercaptopropionic acid group (SP+3-MP group), the sleep time was significantly decreased while the awakening time was significantly increased, the differences mentioned above were statistical significance (P<0.05). Conclusions: Sedative and hypnotic effects of Isoflurane had close relationship with the level of substance P in the body, these effects might be achieved by the substance P, which mediated GABA neurons in vLPO.
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