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Objective: To investigate the role of Maresin1 (MaR1) in hepatic ischemia-reperfusion injury (HIRI). Methods: The HIRI model was established and randomly divided into a sham operation group (Sham group), an ischemia-reperfusion group (IR group), and a MaR1 ischemia-reperfusion group (MaR1+IR group). MaR1 80ng was intravenously injected into each mouse's tail veins 0.5h before anesthesia. The left and middle hepatic lobe arteries and portal veins were opened and clamped. The blood supply was restored after 1h of ischemia. After 6h of reperfusion, the mice were sacrificed to collect blood and liver tissue samples. The Sham's group abdominal wall was only opened and closed. RAW267.4 macrophages were administered with MaR1 50ng/ml 0.5h before hypoxia, followed by hypoxia for 8h and reoxygenation for 2h, and were divided into the control group, the hypoxia-reoxygenation group (HR group), the MaR1 hypoxia-reoxygenation group (MaR1 + HR group), the Z-DEVD-FMK hypoxia-reoxygenation group (HR+Z group), the MaR1 + Z-DEVD-FMK hypoxia-reoxygenation group (MaR1 + HR + Z group), and the Con group without any treatment. Cells and the supernatant above them were collected. One-way analysis of variance was used for inter-group comparisons, and the LSD-t test was used for pairwise comparisons. Results: Compared with the Sham group, the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), interleukin (IL)-1β, and IL-18 in the IR group were significantly higher (P < 0.05), with remarkable pathological changes, while the level in the MaR1 + IR group was lower than before (P < 0.05), and the pathological changes were alleviated. Compared with the Con group, the HR group had higher levels of IL-1β and IL-18 (P < 0.05), while the MaR1 + HR group had lower levels of IL-1β and IL-18 (P < 0.05). Western blot showed that the expressions of caspase-3, GSDME, and GSDME-N were significantly higher in the HR group and IR group than in the other groups; however, the expression was lower following MaR1 pretreatment. The Z-DEVD-FMK exploration mechanism was inhibited by the expression of caspase-3 in HIRI when using MaR1. Compared with the HR group, the IL-1β and IL-18 levels and the expressions of caspase-3, GSDME, and GSDME-N in the HR + Z group were decreased (P < 0.05), while the expression of nuclear factor κB was increased, but following MaR1 pretreatment, nuclear factor κB was decreased. There was no significant difference in the results between the MaR1 + H/R group and the MaR1 + H/R + Z group (P > 0.05). Conclusion: MaR1 alleviates HIRI by inhibiting NF-κB activation and caspase-3/GSDME-mediated inflammatory responses.
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Camundongos , Animais , NF-kappa B/metabolismo , Interleucina-18/metabolismo , Caspase 3/metabolismo , Fígado/patologia , Transdução de Sinais , Traumatismo por Reperfusão/metabolismoRESUMO
Objective To evaluate the protective effect of Bletilla striata polysaccharide ( BSPS) on immunological and chemical liver injury in mice. Methods Thirty Kunming male mice were randomly divided into five groups, including the normal control group,model control group,and low-,middle-,and high-dose BSPS groups (n=6 each).Tail vein injection of ConA was carried out to establish the ConA-induced liver injury model.After different treatments,all the animals were sacrificed,and the plasma levels of ALT and AST were tested.Additionally,sixty Kunming male mice were randomly divided into six groups,including the normal control group,model control group,silymarin group,and low-,middle-,and high-dose BSPS groups (n=10 each).Tail vein injection of CCl4 was performed to establish the CCl4-induced acute liver injury model.After different treatments,the plasma levels of ALT and GSH were tested.The effects of BSPS on the weights of the liver and spleen were examined. Results The levels of ALT and AST were reduced in BSPS-treated mice when compared with those experiencing only ConA-induced liver injury ( model control group) ,and significant difference was found between the middle-and high-dose BSPS groups and the model control group (P<0.01,P<0.05).The weights of the liver and spleen and the level of ALT were reduced in BSPS-treated mice as compared with those with only CCl4-induced acute liver injury (model control group),while the level of GSH was significantly increased in middle-and high-dose BSPS groups (P<0.05). Conclusion BSPS at low,middle,and high doses can prevent against the ConA-induced immunological liver injury and CCl4-induced acute liver injury in mice.
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Objective To investigate the protective effects of ethanol extracts of Tadehagi triquetrum ( TTOE) on car-bon tetrachloride ( CCl4 )-induced acute liver injury in mice. Methods Kunming mice were randomly divided into six groups:normal control group ( NC group) ,model control group,bifendate dropping pill group,low-,medium-and high-dose TTOE groups. The liver injury model was established by administration of CCl4 in all the groups except the NC group.The indexes of the liver, spleen and thymus were obtained.The activities of serum ALT,AST,ALP,LDH, albumin and T-AOC were measured.The activi-ties of SOD and GSH-PX and the contents of MDA,NO and GSH and Cyt P450 were also detected in hepatic tissues. Results TTOE at different doses could obviously reduce the indexes of the liver,thymus and spleen,which were (57.13±0.71),(32.44± 0.24),and (27.78±0.16),respectively,in high-dose TTOE group,and there were significant differences between the TTOE groups and model control group (P<0.01).The activities of ALT,AST,ALP and LDH were obviously decreased in high-dose TTOE groups,which were (65.59±8.23),(141.38±15.52),(2 462.4±253.6),(172.51±20.64),respectively,in the TTOE high-dose group (P<0.01).The serum levels of Alb and T-AOC were obviously increased,the contents of NO and MDA significantly decreased and the activities of SOD and GSH-PX and the contents of GSH Cyt P450 in liver tissues profoundly increased in TTOE groups when compared with those in model control group ( P<0.05 or P<0.01) . Conclusion TTOE could protect against acute hepatic injury induced by CCl4 in mice,which may be associated with the decrease in the activities of liver enzymes,anti-oxide free radical effect,decreased NO content and inhibited lipid peroxidation.
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Objective To study the protective effect and mechanism of Inonotus obliquus polysaccharide on liver injury induced by isoniazid( INH) combined with rifampicin( RFP) in mice. Methods Forty-eight mice were randomly divided into six groups ( control, model, huganpian, Inonotus obliquus polysaccharide at low, middle, and high dose ) . The mice were administered orally with isoniazid and rifampicin simultaneously except the control. After 2 h,the control and model groups were administered with normal saline,and others were treated with huganpian and Inonotus obliquus polysaccharide,respectively,once a day for 2 weeks. The liver index and serum levels of ALT and AST,malondialdehyde(MDA),superoxide dismutase(SOD) and glutathione peroxidase( GPx) were measured. Pathology examination of liver tissue was performed. Results The activities of ALT and AST, liver index, content of MDA in liver homogenate of mice treated with Inonotus obliquus polysaccharide and huganpian decreased obviously, while the liver SOD activity increased. Histopathological exzamination showed that Inonotus obliquus polysaccharide alleviated the degeneration and necrosis of hepatic cells. Conclusion Inonotus obliquus polysaccharide shows protective effects on mice with hepatic toxic injury induced by isoniazid and rifampicin,which maybe due to its antioxidation effect.
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Objective To investigate whether protease inhibitor (ulinastatin, UTI) can protect liver from ischemia-reperfusion injury in hepatocellular carcinoma (HCC) patients undergoing hepatectomy after hepatic inflow occlusion. Methods A prospective randomized control study was designed. Thirty-one HCC patients undergoing hepatectomy after hepatic inflow blood occlusion were randomly divided into the following two groups. UTI group (n=16), 1?105 units of ulinastatin was given intravenously in operation, then the dosage was continuously used twice a day up to 5 days postoperatively. Control group (n=15), the patients received other liver protective drugs. Liver function, plasma C-reactive protein (CRP) and cortisol level were compared between these two groups. Results The postoperative liver function of the UTI group was significantly improved compared with the control group. For example, on the third postoperative day the aspartate transaminase (AST), alanine transaminase (ALT) and total bilirubin level in the UTI group were significantly lower than those in the control group, respectively (P
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Objective: To explore the parameters used for the clinical evaluation of post-trau- matic hepatic function crashing down to the ground. Methods: By establishing the animal model of liver impact injury in simulation of parachuter,blood were sampled before injuries and 15 min, 30 min,45 min,1 h, 3 h, 6 h ,9 h after injuries. Cytokines including TNF?、IL-2 and liver function parameters including ALT,AST,LD-L,GGT,ALP were measured and analyzed statistically. Results: TNF? increased after 15 min- utes, and IL-2 increased after 30 minutes(P0.05). These two pa- rameters were significantly increased all the time after injuries(P
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Objective:To investigate the expression of costimulatory molecule B7-1 and B7-2 by warm ischemia/reperfusion(I/R)injury in rat liver and the meaning of immunology.Methods:Male Wistar rats were randomly divided into 3 groups:A(ischemia 30 mins,referfusion 24h),B(ischemia 60 mins,referfusion 24h),C(sham operation group).A model of hepatic warm I/R in rats was established according to the method of Ohmorid.The expression of B7-1 and B7-2 mRNA was analyzed by real-time reverse transcription polymerase chain reaction(RT-PCR).Results:Compared with the sham operation group,the expression of B7-1 and B7-2 mRNA increased significantly in the rats undergoing I/R procedure(P