| Background Sepsis is defined as the acute systemic inflammatory response to infection with a clinical spectrum ranging from hemodynamic changes to multiple organ dysfunction syndrome. Sepsis still has three characteristics of a high morbidity, high cost of treatment, high mortality. Acute liver injury(ALI) is a frequent and serious complication of sepsis. A growing body of evidence now suggests that inflammatory reactions induced by oxidative stress involved in the mechanisms of the sepsis-induced ALI. Recent studies suggest that paeoniflorin(PF)is involved in antioxidant. Nrf2-ARE pathway is known as the important antioxidant system. The role of PF in the pathogenesis of ALI induced by sepsis and its regulatory antioxidation mechanisms remain unclear.Objective This study aimed to observe the early protective effect of PF on cecal ligation and puncture(CLP)-induced sepsis ALI in rats and the expression of Nrf2/γ-GCS, then explore the antioxidative of PF in ALI.Methods Thirty-six adult male Sprague Dawley( SD) rats were randomly divided into 3 groups in the study, and 12 for each. The septic rats model with ALI was reproduced by method of CLP. Control rats(Sham CLP, SCLP) received opening abdominal surgery without ligation and puncture of the cecum. CLP rates were treated with or without rejecting PF(90mg/kg,15 mg/ml)in the abdomen after operating. The rats in the intervention group were rejected with PF in the abdomen at a dosage of 90mg/kg after operating. Observed the symptoms and the survival situation of rats in each group within 48 h. Counted rats at the different time points, and draw survival curves. Another 30 rats, the same three groups and intervention. At 6h after treatment, measureed alanine aminotransferase(ALT)in serum by the naked eye. Observed the pathological changes in the liver with HE coloration. Tested the content of MDA by thiobarbituric acid method and the activity of SOD by xanthine oxidase method. The levels of TNF-α and IL-6 in tissue were analyzed using commercially available ELISA kits; Western Blot was applied for detection of Nrf2 and γ-GCS protein expression;Real-Time PCR was applied for detection of Nrf2/γ-GCS m RNA expression.Results The survival rate within 48 h of rats in the intervention group was increased significantly(66.7% vs 16.7%,χ2 = 4. 248, p <0. 05). In the PF group, the level of ALT in serum(365.11±13.22 vs 467.00±18.08, p<0.01) were all significantly lower than that in the model group. The content of MDA in the rats of rejecting PF were decreased significantly(1.85±0.17 vs 2.60±0.272.60±0.27, p<0.01) than that in the model group, but the activity of SOD was enhanced(2.65±0.11vs1.58±0.24, p<0.01). In the SCLP rats, the hepatocytes were no obvious abnormalities with HE staining. However, infiltration of quantity inflammatory cells and large necrosis were seen in sinusoids area. Liver injury was obviously relieved in the PF intervention rats compared to that in the model rats, with spotty necrosis in some hepatocytes and karyo-kinesis. the expression of Nrf2 protein(0.1073±0.012 vs0.0731± 0.016,p=0.003), the expression of γ-GCS protein(0.1124±0.021vs0.0613± 0.026,p<0.01), the expression of Nrf2 m RNA(3.7758±0.557 vs0.7430± 0.164,p<0.01) and γ-GCS m RNA(1.6001±0.279 vs0.9646±0.126,p<0.01) were all significantly higher than that in the model rats.Conclusion In summary, PF protects against sepsis-induced ALI through Inhibiting the inflammatory response, Nrf2 and γ-GCS up-regulation. |
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