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Inhibitory Effects of Dexmedetomidine and Propofol on Gastrointestinal Tract Motility Involving Impaired Enteric Glia Ca2+ Response in Mice

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Abstract

Propofol and dexmedetomidine are popular used for sedation in ICU, however, inadequate attention has been paid to their effect on gastrointestinal tract (GIT) motility. Present study aimed to compare the effect of propofol and dexmedetomidine on GIT motility at parallel level of sedation and explore the possible mechanism. Male C57BL/6 mice (8–10 weeks) were randomly divided into control, propofol and dexmedetomidine group. After intraperitoneal injection of propofol or dexmedetomidine, comparable sedative level was confirmed by sedative score, physiological parameters and electroencephalogram (EEG). Different segments of GIT motility in vivo (gastric emptying, small intestine transit, distal colon bead expulsion, stool weight and number of fecal pellets, gastrointestinal transit and whole gut transit time) and colonic migrating motor complexes (CMMCs) pattern in vitro were evaluated. The Ca2+ response of primary enteric glia was examined under the treatment of propofol or dexmedetomidine. There is little difference in physiological parameters and composite permutation entropy index (CPEI) between administration of 50 mg/kg propofol and 40 μg/kg dexmedetomidine, indicated that parallel level of sedation was reached. Data showed that propofol and dexmedetomidine had significantly inhibitory effect on GIT motility while dexmedetomidine was stronger. Also, the amplitude (ΔF/F0) of Ca2+ response in primary enteric glia was attenuated after treated with the sedatives while the effect of dexmedetomidine was greater than propofol. These findings demonstrated that dexmedetomidine caused stronger inhibitory effects on GIT motility in sedative mice, which may involve impaired Ca2+ response in enteric glia. Hence, dexmedetomidine should be carefully applied especially for potential GIT dysmotility patient.

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Acknowledgements

We are especially grateful for the generous help of Professor Shengxi Wu and his colleagues: Professor Xi Wang, Professor Yazhou Wang, and Haifeng Zhang (Department of Neurobiology, Air Force Medical University, Xi’an, Shaanxi Province, China) in supporting of experiment.

Funding

This work was supported by the National Natural Science Foundation of China (Grants number 81801899, 81774113 and 81974540).

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All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by YL, YW, HC, BC, JM, HH and SL. The first draft of the manuscript was written by LH and QW. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Qiang Wang.

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Li, Y., Wang, Y., Chang, H. et al. Inhibitory Effects of Dexmedetomidine and Propofol on Gastrointestinal Tract Motility Involving Impaired Enteric Glia Ca2+ Response in Mice. Neurochem Res 46, 1410–1422 (2021). https://doi.org/10.1007/s11064-021-03280-7

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