Cannabidiol improves rhythmic disorders due to propofol anaesthesia

WANG Yankai; LI Jincao; WU Xinshun; LI Shuo; XUE Rui; FAN Qiongyin; ZHANG Yang; ZHANG Youzhi; GUO Zhenggang

doi:10.3969/j.issn.2097-1753.2025.02.005

Abstract：Objective To investigate the effect of cannabidiol(CBD)on propofol(PPF)-induced sleep rhythm disturbances in rats.Methods Twenty-four SD rats were divided into the control(CON)group,model(MOD)group,melatonin(MLT)group,and CBD group,and each group was acclimatized to a 12 h/12 h light/dark rhythm environment for one week.The MLT and CBD groups were given 15 mg·kg-1 melatonin and 10 mg·kg-1 CBD,respectively,by gavage at CT12(circadian time,CT12 was set at 20:00)while the other groups were given an equal volume of solvent.On the same day,all these groups except the CON group were anaesthetized with propofol at CT16(CT16 was set at 22:00).Blood was collected through the fundus sinus vein at 1 h and 24 h after anesthesia and circadian rhythm was monitored for one week.The endogenous melatonin level of rats was detected by ELISA before the CTX-TNA2 cell lines were divided into the negative control(NC)group,6.25,12.50,50.00 and 100.00 μM PPF group,and 2.50,5.00,10.00,20.00,40.00,60.00,80.00 and 100.00 μM CBD group.The cell survival rate was detected using the CCK-8 method.The CTX-TNA2 cell lines were divided into the NC group,PPF group,PPF+2.5 μM CBD group,PPF+5.0 μM CBD group,and PPF+10.0 μM CBD group.The NC group was routinely cultured,the PPF group was cultured for 24 h in medium containing propofol,while the PPF+2.5 μM CBD group,PPF+5.0 μM CBD group and PPF+10.0 μM CBD group were pretreated with media containing different concentrations of CBD for 4 h before being treated with media containing propofol for 24 h.Cellular γ-aminobutyric acid levels were measured by ELISA.Results Compared with the CON group,the circadian rhythm of rats in the MOD group was phase-delayed by 1-3 hours(P＜0.001 or＜0.05),and serum melatonin levels were significantly increased at 1 h after anesthesia(P＜0.001).Compared with the MOD group,serum melatonin levels in the CBD group rats remained at normal levels after anesthesia(P=0.997).Compared with the NC group,the cell survival rate decreased in the 40.00,60.00,80.00 and 100.00 μM CBD group(P＜0.001),but there was no significant difference in cell survival rates between other doses in the PPF and CBD groups compared with the NC group(P＞0.05).Compared with the NC group,the GABA level in the PPF group increased(P=0.014).Compared with the PPF group,the GABA levels in the PPF+2.5 μM CBD group and PPF+5.0 μM CBD group decreased(P=0.002,＜0.001).Conclusion Propofol anesthesia can significantly disrupt normal circadian rhythm and serum melatonin levels in rats.After CBD intervention,circadian rhythm disturbances can be improved and serum melatonin levels can return to normal.CBD can down-regulate GABA levels in PPF induced CTX-TNA2 cells.