ABSTRACT
Objective Metformin (MET) can reduce blood glucose, act against inflammation, lessen oxidative stress and prevent fibrosis. This study was to investigate the protective effect of MET against acute lung injury (ALI) induced by paraquat poisoning (PQP) in rats. Methods Totally 78 healthy adult SPF male SD rats were randomly divided into five groups, normal control, PQP model control, and low-, medium- and high-dose MET. The PQP model was established in the latter four groups of rats by intraperitoneal injection of paraquat solution at 30 mg/kg and, at 2 hours after modeling, the rats in the three MET intervention groups were treated intragastrically with MET at 100, 400 and 800 mg/kg/d respectively, while those in the normal and PQP model control groups with the same amount of normal saline, all for 7 successive days. Six of the animals from each group were sacrificed at 1, 3 and 7 days and their lung tissues harvested for measurement of the wet/dry weight ratio of the pulmonary tissue and contents of superoxide dismutase (SOD) and malondialdehyde (MDA) in the plasma, determination of the levels of serum interleukin-1β (IL-1β), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) by ELISA, and observation of the pathological changes in the pulmonary tissue by HE staining. Results In the normal control, PQP model control and low-, medium- and high-dose MET groups, the contents of MDA were (2.53±0.36), (3.68±0.26), (3.57±0.52), (3.56±0.83) and (3.68±0.60) nmol/mL respectively on the 1st day of intervention and (2.53±0.36), (5.18±0.56), (5.09±0.88), (3.80±0.91) and (3.96±0.78) nmol/mL at 7 days; those of SOD were (256.18±18.18), (229.24±18.26), (224.65±19.27), (223.20±19.37) and (226.45±11.62) U/mL on the 1st day and (256.18±18.18), (152.06±17.03), (150.76±18.18), (205.95±13.16) and (208.37±12.23) U/mL at 7 days; those of IL-1β were (10.57±2.24), (21.97±5.03), (22.33±4.88), (21.78±5.21) and (22.11±4.19) pg/mL on the 1st day and (10.57±2.24), (91.86±8.40), (91.36±10.65), (63.52±7.06) and (60.35±6.70) pg/mL at 7 days; those of IL-6 were (21.35±2.62), (45.61±3.71), (44.83±5.97), (46.17±7.33) and (45.78±6.55) pg/mL on the 1st day and (21.35±2.62), (84.38±10.21), (85.88±6.70), (49.08±7.70) and (50.26±7.65) pg/mL at 7 days; and those of TNF-α were (32.37±3.74), (71.89±6.98), (72.52±8.23), (71.13±4.50) and (70.15±6.47) pg/mL on the 1st day and (32.37±3.74), (197.04±14.80), (201.59±13.61), (140.17±14.84) and (139.86±11.12) pg/mL at 7 days. Compared with the normal controls, the rats in the PQP model control and the MET intervention groups showed significant increases in the wet/dry weight ratio of the pulmonary tissue and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but a decrease in the SOD level in the plasma at 1, 3 and 7 days (P < 0.05). In comparison with the PQP model controls, the animals in the medium- and high-dose MET groups exhibited remarkable decreases in the wet/dry weight ratio of the lungs and contents of MDA, IL-1β, IL-6 and TNF-α (all P < 0.05), but an increase in the SOD level at 7 days (P < 0.05). Massive inflammatory cell infiltration, diffuse pulmonary hemorrhage, alveolar collapse and extensive alveolar septal thickening were observed in the PQP model control and low-dose MET groups but significantly alleviated in the medium- and high-dose MET groups at 7 days. Conclusion Metformin can protect paraquat-poisoned rats against acute lung injury by reducing pulmonary edema and the expressions of inflammation- and oxidation-related factors in the pulmonary tissue.
ABSTRACT
ObjectiveThe mechanism of paraquat poisoning (PQP) inducing acute lung injury is not clear. Nuclear factor erythroid 2-related factor 2 (Nrf2 )-antioxidant response element (ARE) is found to be a most important endogenous antioxidant defense pathway. This study aimed to explore the protective effect of 5- amino salicylic acid (5-ASA) against PQP-induced acute lung injury by activating the Nrf2-ARE pathway.MethodsEighty healthy adult male SD rats were randomly divided into four groups: blank control, 5-ASA control, PQP, and 5-ASA treatment. The animals in the PQP and 5-ASA treatment groups were injected with paraquat at 20 mg/kg into the left abdominal cavity for construction of the PQP model and those in the blank and 5-ASA control groups with isotonic saline at 1 mL. At 2 hours after modeling, the rats in the 5-ASA control and 5-ASA treatment groups received gavage of 5-ASA 75 at mg/kg for 3 successive days. At 1 and 3 days after observation, all the rats were sacrificed and the lower lobe of the right lung harvested for HE staining and observation of pathologic changes in the lung tissue. Meanwhile the left lung tissue was collected for determination of the expressions of Nrf2 and HO-1 proteins by Western blot.ResultsBehavioral changes were observed in the rats of the PQP and 5-ASA treatment groups, but less obvious in the latter. The alveolar wall capillaries of the rats in the PQP group were expanded and congested significantly, with widened alveolar septa and infiltration of a large number of inflammatory cells at 1 and 3 days, even severer at 3 days. The rats of the 5-ASA treatment group showed obviously reduced edema and the inflammatory cell infiltration at the corresponding time points as compared the PQP group. The lung tissue pathology scores were significantly higher in the 5-ASA treatment and PQP groups than in the blank control at 1 day (0.66±0.10 and 0.61±0.04 vs 0.18±0.05, P<0.05) and at 3 days (0.74±0.08 and 0.49±0.08 vs 0.16±0.02, P<0.05), but markedly lower in the 5-ASA treatment than in the PQP group (P<0.05). Both the expressions of Nrf2 and HO-1 proteins were remarkably higher in the 5-ASA control, PQP and 5-ASA treatment groups than in the blank control at 1 and 3 days (P<0.05), and so were they in the 5-ASA treatment than in the PQP group (P<0.05).Conclusion5-ASA can effectively reduce PQP-induced acute lung injury, which may be related to its up-regulation of the Nrf2 expression.
ABSTRACT
Cardiac arrest during upper abdominal surgery such as liver transplantation is a rare but very severe complication. Traditional external cardiac compression has been the mainstay of basic life support in general circumstances. Subdiaphragmatic cardiac compression (SDCC), with no incision in the diaphragm, may be a more effective measure. This maneuver can provide more effective and timely cardiac compression via the already open abdomen in surgery and not add extra trauma. This method can provide a quicker and more effective means of circulation support for intraoperative cardiac arrest patients without adding new injuries. Five cases are reported and all the patients had return of spontaneous circulation (ROSC). This is the first report of the SDCC method.
Subject(s)
Adult , Female , Humans , Male , Middle Aged , Cardiopulmonary Resuscitation , Methods , Heart Arrest , Therapeutics , Liver TransplantationABSTRACT
<p><b>OBJECTIVE</b>To investigate the effect of rhizoma paridis total saponins(RPTS)on the levels of tumor necrosis factor alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interleukin-6 (IL-6) in blood serum of two-hit rat model induced by multiple fractures and lipopolysaccharide.</p><p><b>METHODS</b>Sixty-eight Wistar rats were randomly divided into five groups. The models were made in four groups (expect the blank control group) in accordance with the standard of two-hit animal model induced by multiple fractures and lipopolysaccharide. At 1 hour after models made,the rats in RPTS groups were given rhizoma paridis total saponins with different concentrations by intragastric administration. Six hours later, the concentrations of TNF-alpha, IL-1 beta and IL-6 in the blood serum of all rats were detected by ELISA (enzyme linked immunosorbent assay).</p><p><b>RESULTS</b>The concentrations of TNF-alpha, IL-1 beta and IL-6 in blood serum of rats in the model group were remarkably higher than those in the blank control group (P<0.001), and these in the RPTS groups were remarkably lower than those in the model group (P<0001).</p><p><b>CONCLUSION</b>RPTS can decrease the levels of TNF-alpha and IL-6 and IL-1 beta in the blood serum of rats subjected to two-hit induced by multiple fractures and lipopolysaccharide.</p>