Purpose Dexmedetomidine (DEX) stabilizes intraoperative blood glucose levels and reduces insulin resistance (IR), a common perioperative complication. However, the molecular mechanisms underlying these effects remain unclear. Since endoplasmic reticulum stress (ERS) is a mechanism of IR, this study sought to examine whether DEX can effectively alleviate IR by reducing ERS. Methods HepG2 and LO2 cells were treated with different concentrations of insulin. The glucose content assay and Cell Counting Kit-8 (CCK-8) were then employed to determine the optimal insulin concentration capable of inducing IR without affecting cell viability. Insulin-resistant hepatocytes were cultured with different concentrations of DEX for 24 h, and the glucose concentration in the supernatant was measured. ERS was assessed by qPCR and western blotting. The latter was also used to quantify the expression of phosphorylated protein kinase B (p-AKT), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6 phosphatase (G6Pase), which are key proteins involved in the action of insulin. Results After 48-h of culturing with 10 μg/mL insulin, glucose consumption in hepatocytes was found to be reduced. IR hepatocytes cultured with 10, 100, or 1000 ng/ml DEX for 24 h showed a concentration-dependent increase in glucose consumption. Elevated mRNA and protein levels of ERS markers binding immunoglobulin protein (BIP) and ER protein 29 (ERp29), were reversed by DEX treatment. Moreover, reduced p-AKT and increased PEPCK and G6Pase protein levels in IR hepatocytes were also restored following DEX treatment. Conclusion DEX may alleviate IR in hepatocytes by reducing ERS serving to restore insulin action via the IRS-1/PI3K/AKT pathway.
Background To observe the effects of different positive end-expiratory pressure (PEEP) ventilation strategies on pulmonary compliance and complications in patients undergoing robotic-assisted laparoscopic prostate surgery. Methods A total of 120 patients with the American Society of Anesthesiologists Physical Status Class I or II who underwent elective robotic-assisted laparoscopic prostatectomy were enrolled. We randomized the patients divided into divided into three groups of 40 patients each: PEEP0, PEEP5, or PEEP10. Master Anesthetist used volume control ventilation intraoperatively with an intraoperative deep muscle relaxation strategy. Respiratory mechanics indexes were recorded at six time-points: 10 mimuts after anaesthesia induction, immediately after pneumoperitoneum establishment, 30 min, 60 min, 90 min, and at the end of pneumoperitoneum. Arterial blood gas analysis and oxygenation index calculation were performed 10 mimuts after anaesthesia induction, 60 mimuts after pneumoperitoneum, and after tracheal extubation. Postoperative pulmonary complications were also recorded. Results After pneumoperitoneum, peak inspiratory pressure (Ppeak), plateau pressure (Pplat), mean pressure (Pmean), driving pressure (ΔP), and airway resistance (Raw) increased significantly, and pulmonary compliance (Crs) decreased, persisting during pneumoperitoneum in all groups. Between immediately after pneumoperitoneum establishment, 30 min, 60 min, and 90 min, pulmonary compliance in the 10cmH2OPEEP group was higher than in the 5cmH2OPEEP (P < 0.05) and 0cmH2OPEEP groups(P < 0.05). The driving pressure (ΔP) immediately after pneumoperitoneum establishment, at 30 min, 60 min, and 90 min in the 10cmH2OPEEP group was lower than in the 5cmH2OPEEP (P < 0.05) and 0cmH2OPEEP groups (P < 0.05). Sixty min after pneumoperitoneum and tracheal extubation, the PaCO2 did not differ significantly among the three groups (P > 0.05). The oxygenation index (PaO2/FiO2) was higher in the PEEP5 group than in the PEEP0 and PEEP10 groups 60 min after pneumoperitoneum and after tracheal extubation, with a statistically significant difference (P < 0.05). In postoperative pulmonary complications, the incidence of atelectasis was higher in the PEEP0 group than in the PEEP5 and PEEP10 groups, with a statistically significant difference (p < 0.05). Conclusion The use of PEEP at 5cmH2O during RARP increases lung compliance, improves intraoperative oxygenation index and reduces postoperative atelectasis. Trial registration This study was registered in the China Clinical Trials Registry on May 30, 2020 (Registration No. ChiCTR2000033380).
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