摘要
PURPOSE: Research has shown that sevoflurane-induced toxicity causes neurodegeneration in the developing brain. miR-34a has been found to negatively regulate ketamine-induced hippocampal apoptosis and memory impairment. However, the role of miR-34a in sevoflurane-induced hippocampal neurodegeneration remains largely unclear. MATERIALS AND METHODS: C57/BL6 mice (7-day-old) inhaled 2.3% sevoflurane for 2 h/day over 3 consecutive days. miR-34a expression was reduced through intracerebroventricular injection with miR-34a interference lentivirus vector (LV-anti-miR-34a) into mouse hippocampus after anesthesia on the first day of exposure. Hippocampal apoptosis was detected by TUNEL assay and flow cytometry analysis. Spatial memory ability was evaluated by the Morris water maze test. The interaction between miR-34a and Wnt1 was confirmed by luciferase reporter assay, RNA immunoprecipitation, Western blot, and immunofluorescence staining. The effects of miR-34a on protein levels of B-cell lymphoma 2 (Bcl-2), bcl-2-like protein 4 (Bax), and Wnt/β-catenin pathway-related proteins were evaluated using Western blot analysis. RESULTS: Sevoflurane upregulated hippocampal miR-34a, and miR-34a inhibitor attenuated sevoflurane-induced hippocampal apoptosis and memory impairment. miR-34a negatively regulated Wnt1 expression by targeting miR-34a in hippocampal neurons. Moreover, forced expression of Wnt1 markedly undermined miR-34a-mediated enhancement of sevoflurane-induced apoptosis of hippocampal neurons, while Wnt1 silencing greatly restored anti-miR-34a-mediated repression of sevoflurane-induced apoptosis of hippocampal neurons. Increased expression of miR-34a inhibited the Wnt/β-catenin pathway in hippocampal neurons exposed to sevoflurane, while anti-miR-34a exerted the opposite effects. CONCLUSION: miR-34a inhibitor may effectively protect against sevoflurane-induced hippocampal apoptosis via activation of the Wnt/β-catenin pathway by targeting Wnt1.
Subject(s)
Animals , Mice , Anesthesia , Apoptosis , Blotting, Western , Brain , Flow Cytometry , Fluorescent Antibody Technique , Hippocampus , Immunoprecipitation , In Situ Nick-End Labeling , Lentivirus , Luciferases , Lymphoma, B-Cell , Memory , Neurons , Repression, Psychology , RNA , Spatial Memory , Water摘要
ObjectiveTo investigate the efficacy of different methods of anesthesia for laparoscopic hysterectomy.MethodsSixty ASA Ⅰ or Ⅱ patients,aged 45-60 yr,weighing 55-65 kg,scheduled for laparoscopic hysterectomy,were equally and randomly divided into 2 groups:combined intravenous-inhalational anesthesia group (group Ⅰ ) and combined spinal-epidoral anesthesia (CSEA) + general anesthesia group (group Ⅱ ).In group Ⅰ,anesthesia was maintained with inhalation of sevoflurane and infusion of remifentanil after induction of anesthesia.In group Ⅱ,CSEA was performed,after the upper level of sensory block was stable,general anesthesia was induced and maintained with inhalation of sevoflurane,and state entropy (SE) was naintained at 45-60.Arterial blood samples were taken to determine the plasma concentrations of adrenaline ( AE ),norepinephrine (NE) and dopamine (DA) after admission to the operation room,after completion of pneumoperitoneum,at 10 min after pneumopentoneum,during uterus traction,during removal of the laryngeal mask airway,and at 10 min after removal of the laryngeal mask airway (T0-5).The time for recovery of spontaneous breathing,extubation time,and time of regaining consciousness were recorded at the end of operation.The side-effects and number of patients requiring increments of analgesics were also recorded within 48 h after operation.Patient' s satisfaction was recorded at 48 h after operation.ResultsCompared with group Ⅰ,the plasma concentrations of AE and NE at T3-5 and the plasma concentrations of DA at T3,5 were significantly decreased,the time for recovery of spontaneous breathing,extubation time,and time of regaining corsciousess were significantly shortened,and the incidence of agitation and the number of patients requiring increments of analgesics were significantly decreased in group Ⅱ ( P <0.05).There was no significant difference in the incidence of intraoperative awareness,and nausea and vomiting after operation,and the level of patient' s satisfaction at 48 h after operation between the two groups ( P > 0.05).ConctusionCSEA + general anesthesia has better efficacy than combined intravenous-inhalational anesthesia when used for laparoscopic hysterectomy.