ABSTRACT
BACKGROUND AND OBJECTIVES: Sepsis is a life-threatening organ dysfunction syndrome arising from uncontrolled inflammatory responses. Liver injury is a crucial factor for the prognosis of sepsis. Camptothecins (CPTs) have been reported to suppress the inflammatory response induced by sepsis. G2, a CPT-bile acid conjugate, has been demonstrated the property of liver targeting in our previous research. This study aimed to research the effects of G2 on liver injury induced by cecal ligation and puncture (CLP). METHODS: C57BL/6 mice were subjected to CLP surgery, and effects of G2 on liver damage and survival rates of CLP-induced mice were evaluated. To detect the related markers of hepatic injury or neutrophil infiltration, inflammatory cytokines and protein levels, hematoxylin-eosin staining assay, corresponding Detection Kits assay, ELISA and Western blot analysis were performed. RESULTS: Intraperitoneal administration of G2 reduced liver injury and enhanced the survival rates in mice with sepsis. Treatment with G2 decreased the levels of hepatic injury markers aspartate aminotransferase (AST) and alanine aminotransferase (ALT) in the serum of mice induced by CLP. The hepatic level of neutrophil infiltration marker myeloperoxidase (MPO) was reduced in G2 administration group. And the levels of serum inflammatory cytokines, including Tumor Necrosis Factor-α (TNFα), Interleukin-6 (IL-6) and IL-1ß, were decreased by G2. Furthermore, the results of Western blot analysis indicated that G2 suppressed the up-regulation of NF-κB p-P65 and p-IκBα. It suggested that G2 suppressed the activation of NF-κB signaling pathway. CONCLUSION: G2 alleviated sepsis-induced liver injury via inhibiting the NF-κB signaling pathway.
Subject(s)
Bile Acids and Salts/therapeutic use , Camptothecin/therapeutic use , Liver Diseases/etiology , NF-kappa B/metabolism , Sepsis/complications , Signal Transduction/drug effects , Alanine Transaminase/blood , Animals , Aspartate Aminotransferases/blood , Bile Acids and Salts/administration & dosage , Blotting, Western , Camptothecin/administration & dosage , Cytokines/blood , Disease Models, Animal , Enzyme-Linked Immunosorbent Assay , Liver Diseases/metabolism , Liver Diseases/prevention & control , Male , Mice , Mice, Inbred C57BL , Peroxidase/metabolismABSTRACT
<p><b>OBJECTIVE</b>To compare the safety of intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) in ischemic patients under the guidance of CT and multi-mode MRI.</p><p><b>METHODS</b>The clinical, laboratory, and radiologic data from 113 consecutive hyperacute ischemic patients who received intravenous rtPA therapy from June 2009 to October 2011 was retrospectively reviewed. The rate of hemorrhagic transformation (HT) and the clinical outcome between CT and multi-mode MRI was compared. Etiological subgroups were classified according to Chinese ischemic stroke subclassification (CISS).</p><p><b>RESULTS</b>Among 113 patients treated with intravenous rtPA, the mean age was 66 ±12 years, 74(65.5%) were man, the pretreatment National Institutes of Health Stroke Scale score (NIHSS) was 12.4 ±6.5, and time from symptom onset to therapy was 259.7 ±131.7 min. Postlytic radiological HT was found in 34 patients (30.1%). Symptomatic ICH occurred in 9 patients (8%). Logistic regression analysis suggested that multi-mode MRI was an independent predictor of reduced risk of HT.</p><p><b>CONCLUSION</b>The risk of hemorrhagic complications is lower in patients receiving intravenous thrombolytic therapy with rtPA guided by multi-mode MRI than those guided by CT scan.</p>
