ABSTRACT
Objective:To investigate the role and mechanism of splenic myeloid-derived suppressor cells (MDSCs) in sepsis-induced adrenal injury (SAI).Methods:Thirty male C57 mice aged 6-8 weeks were randomly divided into normal control group ( n = 5), sham operation group (Sham group, n = 5), sepsis model group [cecal ligation and perforation (CLP) group, n = 10] and sepsis+splenectomy group (CLPS group, n = 10). The sepsis model of mice was reproduced by CLP method. In Sham group, only the cecum was opened and separated, then closed, without CLP. In CLPS group, the spleen was removed before CLP. In normal control group, no challenge was given. After 24 hours, the rats were sacrificed by anesthesia, and peripheral blood, spleen, bone marrow, and bilateral adrenal glands were harvested. The pathological of adrenal gland was assessed by hematoxylin-eosin (HE) staining under optical microscope. The ratio of MDSCs in peripheral blood, spleen and bone marrow was determined by flow cytometry. The expressions of MDSCs surface antigen CD11b, Gr-1 and interleukins (IL-6, IL-1β) mRNA in adrenal tissue were measured by real-time quantitative reverse transcription-polymerase chain reaction (RT-PCR). Western Blot was used to detect the expressions of mammalian rapamycin target protein (mTOR) pathway related proteins including total mTOR (T-mTOR), phosphorylation of mTOR (p-mTOR) and caspase-3. Results:The adrenal cortex and medulla of the normal control group and Sham group were intact and the structure was clear under optical microscope, while in the CLP group, the adrenal gland showed edema, cortical hemorrhage and cell edema. Compared with the CLP group, the adrenal tissue injury was significantly reduced in the CLPS group. Compared with the normal control group and Sham group, MDSCs ratio in the peripheral blood was significantly increased and significantly reduced in the spleen in the CLP group, but there was no significant difference in bone marrow, the expression levels of CD11b, Gr-1, IL-6, IL-1β mRNA and caspase-3 protein were increased significantly and p-mTOR protein expression was significantly decreased in adrenal tissue, there was no significant difference in the expression of T-mTOR protein. Compared with the CLP group, in the CLPS group, the MDSCs ratio in the peripheral blood was significantly decreased (0.143±0.011 vs. 0.324±0.023, P < 0.01), the expression levels of CD11b, Gr-1, IL-6 , IL-1β mRNA and caspase-3 protein in adrenal gland were significantly decreased [CD11b mRNA (2 -ΔΔCt): 2.90±0.56 vs. 5.74±0.13, Gr-1 mRNA (2 -ΔΔCt): 2.71±0.14 vs. 4.59±0.46, IL-6 mRNA (2 -ΔΔCt): 2.44±0.64 vs. 5.17±1.04, IL-1β mRNA (2 -ΔΔCt): 3.58±0.52 vs. 4.44±0.26, caspase-3 protein (caspase-3/GAPDH): 0.05±0.01 vs. 0.13±0.02, all P < 0.01], the p-mTOR protein expression was significantly increased (p-mTOR/GAPDH: 0.61±0.11 vs. 0.27±0.04, P < 0.01). Conclusions:The spleen is the major source of MDSCs in SAI. Splenectomy can attenuate SAI by reducing mobilization of MDSCs and activating the mTOR signaling pathway.
ABSTRACT
Objective To explore the feasibility of Narcotrend index (NTI) for digital monitoring of light sedation depth in patients undergoing short-term mechanical ventilation after pancreaticoduodenectomy. Methods A prospective randomized controlled trial was conducted. Patients with mechanical ventilation for 12-48 hours after pancreaticoduodenectomy admitted to department of critical care medicine of the First Affiliated Hospital of Wannan Medical College from January 2016 to December 2018 were enrolled. They were randomly divided into two groups, and NTI and Richmond agitation-sedation score (RASS) were used to guide light sedation treatment respectively. The implementation effect of light sedation, duration of mechanical ventilation, dosage of sedative drugs, occurrence of adverse events (accidental extubation, delirium, cardiovascular events) and stress response [cortisol, epinephrine, norepinephrine, C-reactive protein (CRP)] were compared between the two groups. Results A total of 87 patients were enrolled in this study, of whom 45 received NTI-guided sedation assessment and 42 received RASS-guided sedation assessment. There were no significant differences in gender, age, body mass index (BMI), liver function classification, operation time, blood loss, conversion to laparotomy and acute physiology and chronic health evaluation Ⅱ (APACHEⅡ) score between the two groups. During sedation treatment, the light sedation compliance rate after light sedation, 2, 4, 6 hours and cumulative compliance period number (Dt) in NTI group were higher than those in RASS group [71.1% (32/45) vs. 50.0% (21/42), 80.0% (36/45) vs. 54.8% (23/42), 88.9% (40/45) vs. 59.5% (25/42), 83.9% (642/765) vs. 62.8% (475/756), all P < 0.05]. The dosage of dexmedetomidine in NTI group was higher than that in RASS group (μg·kg-1·h-1:0.60±0.10 vs. 0.54±0.12, P < 0.01), but more patients in RASS group receiveda larger dose of propofol to maintain sedation [ratio of use of propofol: 64.3% (27/42) vs. 37.8% (17/45), dose of propofol (mg/h): 47.82±7.31 vs. 30.83±10.35, both P < 0.05]. The sedation duration and duration of mechanical ventilation in NTI group were lower than those in RASS group (hours: 15.68±2.43 vs. 17.29±2.43, 16.27±2.42 vs. 18.25±2.04, both P < 0.01). There were no significant differences in hypertension, bradycardia, accidental extubation and delirium between the two groups during sedation treatment, but the incidence of hypotension in RASS group was higher than that in NTI group [35.7% (15/42) vs. 13.3% (6/45), P < 0.05]. Compared with RASS group, epinephrine, norepinephrine and the levels of CRP at treatment of 6 hours with light sedation and 2 hours after tracheal catheter removal in NTI group were decreased [epinephrine (pg/L): 138.35±18.60 vs. 157.50±19.91, 136.24±40.40 vs. 150.46±20.22; norepinephrine (pg/L): 347.34±45.46 vs. 393.75±49.77, 340.59±50.95 vs. 376.37±49.70; CRP (μg/L): 62.26±18.78 vs. 71.31±10.32, 53.30±14.47 vs. 64.26±14.69, all P < 0.05], and cortisol level 6 hours after treatment with light sedation was lower than that of RASS group (nmol/L: 327.03±41.04 vs. 358.12±70.01, P < 0.05). Conclusion The application of NTI monitoring to guide light sedation therapy for patients with short-term mechanical ventilation after pancreaticoduodenectomy can better achieve the goal of light sedation.