ABSTRACT
Maresin1 (MaR1) is a new docosahexaenoic acid-derived pro-resolving agent that promotes the resolution of inflammation. In this study, we sought to investigate the effect and underlining mechanisms of MaR1 in modulating alveolar fluid clearance (AFC) on LPS-induced acute lung injury. MaR1 was injected intravenously or administered by instillation (200 ng/kg) 8 h after LPS (14 mg/kg) administration and AFC was measured in live rats. In primary rat alveolar type II epithelial cells, MaR1 (100 nM) was added to the culture medium with lipopolysaccharide for 6 h. MaR1 markedly stimulated AFC in LPS-induced lung injury, with the outcome of decreased pulmonary edema and lung injury. In addition, rat lung tissue protein was isolated after intervention, and we found MaR1 improved epithelial sodium channel (ENaC), Na,K-adenosine triphosphatase (ATPase) protein expression and Na,K-ATPase activity. MaR1 down-regulated Nedd4-2 protein expression though PI3k/Akt but not though PI3k/SGK1 pathway in vivo. In primary rat alveolar type II epithelial cells stimulated with LPS, MaR1-upregulated ENaC and Na,K-ATPase protein abundance in the plasma membrane. Finally, the lipoxin A4 Receptor inhibitor (BOC-2) and PI3K inhibitor (LY294002) not only blocked MaR1's effects on cAMP/cGMP, the expression of phosphorylated Akt and Nedd4-2, but also inhibited the effect of MaR1 on AFC in vivo. In conclusion, MaR1 stimulates AFC through a mechanism partly dependent on alveolar epithelial ENaC and Na,K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway. Our findings reveal a novel mechanism for pulmonary edema fluid reabsorption and MaR1 may provide a new therapy for the resolution of ALI/ARDS.
Subject(s)
Acute Lung Injury/metabolism , Docosahexaenoic Acids/pharmacology , Endosomal Sorting Complexes Required for Transport/metabolism , Epithelial Sodium Channels/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Receptors, Lipoxin/metabolism , Signal Transduction/drug effects , Ubiquitin-Protein Ligases/metabolism , Animals , Lipopolysaccharides , Lung/chemistry , Lung/drug effects , Lung/metabolism , Male , Nedd4 Ubiquitin Protein Ligases , Pulmonary Alveoli/metabolism , Rats , Rats, Sprague-Dawley , Sodium-Potassium-Exchanging ATPase/metabolismABSTRACT
BACKGROUND: Postoperative pain is a concern after thoracic and breast surgeries. Recent studies have demonstrated that ultrasound-guided serratus anterior plane block (SAPB) could provide postoperative analgesia. OBJECTIVE: The objective of this systematic review and meta-analysis was to examine the effects of SAPB on postoperative analgesia in thoracic and breast surgery. STUDY DESIGN: A systematic review and meta-analysis of randomized control trials (RCTs). METHODS: We systematically queried the PubMed, Embase, Web of Science, and Cochrane Library online databases from their establishment through Mar 31, 2022. Eligible RCTs were selected for the purpose of conducting the meta-analysis. The risk of bias of the included trials was assessed by Cochrane Review Manager. The level of certainty was examined utilizing the GRADE (Grade of Recommendations Assessment, Development, and Evaluation) scale to determine whether the evidence was of high quality or not. RESULTS: During the process of the meta-analysis, a total of 27 pieces of literature was included in the present research. SAPB significantly reduced the intraoperative opioid consumption (mean difference [MD] = -9.52 mg of morphine equivalent, 95% CI, -15.50 to -3.54; P < 0.01, I2 = 98%) and postoperative pain opioid consumption (MD = -23.12 mg of morphine equivalent, 95% CI, -30.59 to -15.65; P < 0.01, I2 = 100%. Also, patients in the SAPB group had lower pain scores during the first postoperative 24 hours. Furthermore, SAPB attenuated the occurrence of postsurgical nausea and vomiting, as well as chronic postsurgical pain. LIMITATIONS: Double-blinding was not performed in some trials, also some assessors were not blinded; the included sample sizes of eligible trials which reported the incidence of chronic postsurgical pain were relatively small; the comparisons between SAPB and other types of blocks were not performed in our meta-analysis. CONCLUSION: Our findings suggest that SAPB not only relieves acute pain after thoracic and breast surgery, but also reduces the incidence of chronic postsurgical pain.
Subject(s)
Analgesics, Opioid , Breast Neoplasms , Humans , Female , Randomized Controlled Trials as Topic , Morphine , Pain, Postoperative/drug therapy , Pain, Postoperative/etiology , Breast Neoplasms/complicationsABSTRACT
Acute respiratory distress syndrome is a life-threatening critical syndrome resulting largely from the accumulation of and the inability to clear pulmonary edema. Protectin DX, an endogenously produced lipid mediator, is believed to exert anti-inflammatory and pro-resolution effects. Protectin DX (5 µg/kg) was injected i.v. 8 h after LPS (14 mg/kg) administration, and alveolar fluid clearance was measured in live rats (n = 8). In primary rat ATII epithelial cells, protectin DX (3.605 × 10-3 mg/l) was added to the culture medium with LPS for 6 h. Protectin DX improved alveolar fluid clearance (9.65 ± 1.60 vs. 15.85 ± 1.49, p < 0.0001) and decreased pulmonary edema and lung injury in LPS-induced lung injury in rats. Protectin DX markedly regulated alveolar fluid clearance by upregulating sodium channel and Na, K-ATPase protein expression levels in vivo and in vitro. Protectin DX also increased the activity of Na, K-ATPase and upregulated P-Akt via inhibiting Nedd4-2 in vivo. In addition, protectin DX enhanced the subcellular distribution of sodium channels and Na, K-ATPase, which were specifically localized to the apical and basal membranes of primary rat ATII cells. Furthermore, BOC-2, Rp-cAMP, and LY294002 blocked the increased alveolar fluid clearance in response to protectin DX. Protectin DX stimulates alveolar fluid clearance through a mechanism partly dependent on alveolar epithelial sodium channel and Na, K-ATPase activation via the ALX/PI3K/Nedd4-2 signaling pathway.
Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Docosahexaenoic Acids/therapeutic use , Protective Agents/therapeutic use , Pulmonary Alveoli/drug effects , Acute Lung Injury/chemically induced , Acute Lung Injury/pathology , Animals , Cells, Cultured , Lipopolysaccharides , Lung/drug effects , Lung/pathology , Male , Pulmonary Alveoli/cytology , Pulmonary Alveoli/pathology , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects , Sodium Channels/analysis , Sodium-Potassium-Exchanging ATPase/analysisABSTRACT
The clinical and experimental postcardiac arrest treatment has not reached therapeutic success. The present study investigated the effect of PD98059 (PD) in rats subjected to cardiac arrest (CA)/cardiopulmonary resuscitation (CPR). Experimental rats were divided randomly into 3 groups: sham, CA, and PD. The rats except for sham group were subjected to CA for 5 min followed by CPR operation. Once spontaneous circulation was restored, saline and PD were injected in CA and PD groups, respectively. The survival rates and neurologic deficit scores (NDS) were observed, and the following indices of brain tissue were evaluated: ROS, MDA, SOD, p-ERK1/2/ERK1/2, caspase-3, Bax, Bcl-2, TUNEL positive cells, and double fluorescent staining of p-ERK/TUNEL. Our results indicated that PD treatment significantly reduced apoptotic neurons and improved the survival rates and NDS. Moreover, PD markedly downregulated the ROS, MDA, p-ERK, and caspase-3, Bax and upregulated SOD and Bcl-2 levels. Double staining p-ERK/TUNEL in choroid plexus and cortex showed that cell death is dependent on ERK activation. The findings in present study demonstrated that PD provides neuroprotection via antioxidant activity and antiapoptosis in rats subjected to CA/CPR.