Table 1.
Studies of SPMs in I/R injury experiment models.
| SPMs | Disease model | Action | Mechanisms | References |
|---|---|---|---|---|
| Lipoxin and its analogs | MCAO/reperfusion model | Ameliorating BBB dysfunction. | Inhibiting MMP-9 and increasing TIMP-1 protein expression. | (158) |
| Regulating neutrophil-platelet aggregate (NPA) formation, inhibiting cerebral microvasculature reactivity. | Through binding with ALX/FPR2 | (191) | ||
| Inhibiting 5-lipoxygenase translocation and leukotrienes biosynthesis | Through ERK signal transduction pathway. | (192) | ||
| Suppressing PMNs infiltration and lipid peroxidation levels, inhibiting microglia and astrocytes activation, reducing pro-inflammatory cytokines and up-regulating anti-inflammatory cytokines. | Inhibiting NF-κB activation. | (193) | ||
| Reducing oxidative stress. | Activating Nrf2 pathway and its nuclear translocation, as well as HO-1 expression and GSH synthesis. | (194) | ||
| Mesenteric artery I/R model | Provoking adherent leukocytes detachment from endothelium. | Through binding with ALX/FPR2. | (161, 195) | |
| Decreasing vascular permeability, leukocyte influx, and hemorrhage in intestine, suppressing TNF-α production. | Associated with enhanced IL-10 production. | (179) | ||
| Reducing oxidative stress | Through activating Keap1/Nrf2 pathway. | (184) | ||
| Hindlimb I/R model | Inhibiting PMNs infiltration in remote organs. | (162–164) | ||
| Bilateral common carotid artery occlusion (BCCAO)/reperfusion model | Reducing the number of rolling cells, adherent leukocytes and activated microglial cells, increasing plasma MCP-1 and IL-6 levels. | Through binding with FPR2/3. | (171) | |
| Bilateral kidney I/R model. | Inhibiting PMNs infiltration, reducing IL-1β, IL-6, and GRO-1 expression. | Modulation of renal mRNA levels for the suppressors of cytokine signaling SOCS-1 and SOCS-2. | (180) | |
| Modifing many pathogenic mediators expression, including cytokines, growth factors, adhesion molecules, and proteases. | (181) | |||
| Spinal cord I/R model. | reducing cell apoptosis and MDA levels, increasing SOD activity. | (182) | ||
| Left anterior descending coronary artery I/R model. | Inhibiting neutrophil activation, attenuating myocardial oxidative stress and inhibition of apoptosis, attenuating metabolic disturbance. | downregulation of GRP-78 and caspase-12, upregulating Na+-K+-ATPase expression. | (183, 189) | |
| Permanent MCAO. | Decreasing infarct volume and neurological deficit. | Through agonist of PPARγ. | (186) | |
| Primary cultured astrocytes exposed to OGD/recovery | Reducing oxidative stress. | Through activating Nrf2 pathway. | (185) | |
| Celiac artery I/R model. | Preventing mucosal injury induced by either cyclooxygenase or lipoxygenase inhibitors. | (196) | ||
| Resolvins | Left anterior descending coronary artery occlusion model | 1) Discontinuing neutrophil priming in spleen and LV post-MI. 2) Stimulating macrophages clearance from infarcted area. 3) Reducing ECM gene expression and collagen deposition. |
Reducing pro-fibrotic genes and decreasing collagen deposition. | (152) |
| Decreasing infarct size and attenuating Depression-like symptoms. | (197) | |||
| Left coronary artery I/R model. H9c2 cells exposed to hypoxia /reoxygenation |
Increasing cell viability and decreased apoptosis. | Activation of pro-survival pathways (Akt and ERK1/2). | (198) | |
| Bilateral kidney I/R model. Swine kidney epithelial cells treated with H2O2. |
RvDs reduced kidney interstitial fibrosis. RvDs and PD1 reduced infiltrating leukocytes numbers and activation of macrophages. | Blocking TLR. | (151) | |
| hind LIMB I/R model | Inhibiting PMNs infiltration in remote organs. | (165, 166) | ||
| Hepatic portal triad I/R model | Inhibiting PMNs infiltration, enhancing M2 macrophage polarization and efferocytosis. | (175) | ||
| Attenuating IL-6, TNF-α, and myeloperoxidase levels, reducing apoptosis. | Increasing phosphorylation of Akt. | (199) | ||
| Lung hilum I/R model | Improving energy metabolism disturbance, protecting mitochondrial structure and function and decreasing apoptosis. | Increasing ATP, glycogen content and Na+-K+-ATPase activity, balancing the ratio of ATP/ADP. | (188) | |
| Inhibiting complement, immunoglobulin, and PMNs activation and inflammatory factors expression. | Down-regulating TLR4/NF-κB. | (200) | ||
| Protectins | MCAO/reperfusion model | Improving neurological scores, reducing infarction volumes and edema. | Through activation of Akt and p70S6K pathways. | (201, 202) |
| MCAO/reperfusion model, human neural progenitor cells exposed to IL-1β | Reducing leukocytes infiltration, preventing pro-inflammatory gene expression. | Inhibiting NF-κB activation and cyclooxygenase-2 expression. | (150) | |
| MCAO/reperfusion model, retinal pigment epithelial (RPE) cells exposed to UOS | Protecting cells against death induced by cerebral ischemia and UOS. | Upregulating ring finger protein 146 which facilitated DNA repair. | (203) | |
| Renal pedicles I/R model, glomerular mesangial cells exposed to serum starvation. | Reducing leukocytes infiltration. | Amplifing Reno protective HO-1 protein and mRNA expression. | (168) | |
| Maresins and MCTR | Lung hilum I/R model. | Suppressing oxidative stress. | Through activation of the Nrf-2-mediated HO-1 signaling pathway. | (187) |
| MCAO/reperfusion model. | Mitigating inflammation. | Inhibiting NF-κB activation. | (204) | |
| Hindlimb I/R model. | Inhibiting PMNs infiltration, regulating cell proliferation, and tissue repayment. | Up-regulating Ki67 and Roof plate-specific spondin3 expression. | (205) |
ADP, adenosine diphosphate; ATP, adenosine triphosphate; ALX/FPR2, synonym formyl peptide receptor; BBB, blood brain barrier; ECM, extracellular matrix; ERK, extracellular signal-regulated kinase; GRO-1, growth regulated oncogene-1; GRP-78, glucose-regulated protein; GSH, glutathione; HO-1, haeme oxygenase-1; IL, interleukin; I/R, ischemia/reperfusion; LV, left ventricle; MCAO, middle cerebral artery occlusion; MCP-1, monocyte chemoattractant protein; MCTR, maresin conjugates in tissue regeneration; MDA, malondialdehyde; MI, myocardial infarction; MMP-9, metalloproteinase-9; NF-κB, nuclear factor-κB; Nrf2, nuclear factor erythroid 2-related factor 2; OGD, oxygen-glucose deprivation; PD1, protectin D1; PMN, polymorphonuclear leukocyte; PPARγ, mediated by transcription factor peroxisome proliferator-activated receptors gamma; Rv, resolvin; SOCS, suppressors of cytokine signaling; SOD, superoxide dismutase; TIMP-1, tissue inhibitors of metalloproteinase-1;TLR, toll-like receptor; TNF-α, tumor necrosis factor-α; UOS, uncompensated oxidative stress.