Objective To observe whether metformin (MET) plays a protective role in acute lung injury (ALI) induced by paraquat (PQ) poisoning in rats by activating the AMPK/NF-κB signaling pathway. Methods PQ exposure was used to construct a rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury, and MET intervention was performed. Rat lung tissue samples were collected to evaluate pathological changes in rat lung tissue, the oxidation index, and inflammatory factors; cell viability was detected by CCK-8 assays, and the protein expression levels of phospho-AMPK and phospho-NF-κBp65 in rat lung tissue and RLE-6TN cells were observed by Western blotting. Results Compared with the PQ group, the MET treatment group showed significantly (1) reduced lung wet/dry ratio (W/D: 4.67 ± 0.31 vs. 5.45 ± 0.40, P < 0.001), (2) reduced pathological changes in lung tissue, (3) decreased MDA levels (nmol/mg prot: 2.70 ± 0.19 vs. 3.08 ± 0.15, P < 0.001) and increased SOD and GSH-Px activities (U/mg prot: 76.17 ± 5.22 vs. 45.23 ± 6.58, 30.40 ± 2.84 vs. 21.00 ± 3.20; all P < 0.001) in lung tissue homogenate, (4) reduced levels of IL-1β, IL-6, and TNF-α in lung tissue homogenates (pg/mL: 47.87 ± 5.06 vs. 66.77 ± 6.55; 93.03 ± 7.41 vs. 107.39 ± 9.81; 75.73 ± 6.08 vs. 89.12 ± 8.94; all P < 0.001), (5) increased activity of RLE-6TN cells (%: 0.69 ± 0.09, 0.76 ± 0.06, and 0.58 ± 0.03 vs. 0.50 ± 0.05; all P < 0.05), (6) decreased protein levels of phospho-NF-κBp65 in lung homogenates and RLE-6TN cells (p-NF-κB/NF-κB: 0.47 ± 0.09 vs. 0.81 ± 0.13; 0.26 ± 0.07 vs. 0.79 ± 0.13; all P < 0.01), and (7) upregulated protein expression of phospho-AMPK in lung homogenates and RLE-6TN cells (p-AMPK/AMPK: 0.88 ± 0.05 vs. 0.36 ± 0.12; 0.93 ± 0.03 vs. 0.56 ± 0.15; all P < 0.01). After the addition of the AMPK inhibitor Compound C (Com C), the protein expression levels of phospho-AMPK and phospho-NF-κBp65 returned to baseline. Conclusion MET can effectively alleviate ALI induced by paraquat poisoning and increase the viability of cells exposed to paraquat. The mechanism may be related to the activation of the AMPK/NF-κB pathway, downregulation of inflammatory mediators such as IL-6 and TNF-α, and upregulation of the SOD and GSH-Px oxidation index, and these effects can be inhibited by the AMPK inhibitor Com C.

Objectives: This study conducted a meta-analysis to assess the effectiveness, stability, and safety of mild therapeutic hypothermia (TH) induced by endovascular cooling (EC) and surface cooling (SC) and its effect on ICU, survival rate, and neurological function integrity in adult CA patients. Methods: We developed inclusion criteria, intervention protocols, results, and data collection. The results included outcomes during target temperature management as well as ICU stay, survival rate, and neurological functional integrity. The characteristics of the included population and each study were analyzed. Results: Four thousand nine hundred thirteen participants met the inclusion criteria. Those receiving EC had a better cooling efficiency (cooling rates MD = 0.31[0.13, 0.50], p < 0.01; induced cooling times MD = − 90.45[− 167.57, − 13.33], p = 0.02; patients achieving the target temperature RR = 1.60[1.19, 2.15], p < 0.01) and thermal stability during the maintenance phase (maintenance time MD = 2.35[1.22, 3.48], p < 0.01; temperature fluctuation MD = − 0.68[− 1.03, − 0.33], p < 0.01; overcooling RR = 0.33[0.23, 0.49], p < 0.01). There were no differences in ICU survival rate (RR = 1.22[0.98, 1.52], p = 0.07, I 2 = 0%) and hospital survival rate (RR = 1.02 [0.96, 1.09], p = 0.46, I 2 = 0%), but EC reduced the length of stay in ICU (MD = − 1.83[− 3.45, − 0.21], p = 0.03, I 2 = 49%) and improved outcome of favorable neurological function at discharge (RR = 1.15[1.04, 1.28], p < 0.01, I 2 = 0%). EC may delay the hypothermia initiation time, and there was no significant difference between the two cooling methods in the time from the start of patients' cardiac arrest to achieve the target temperature (MD = − 46.64[− 175.86, 82.58]). EC was superior to non-ArcticSun in terms of cooling efficiency. Although there was no statistical difference in ICU survival rate, ICU length of stay, and hospitalization survival rate, in comparison to non-ArcticSun, EC improved rates of neurologically intact survival (RR = 1.16 [1.01, 1.35], p = 0.04, I 2 = 0%).