| BacgroundSepsis is the systemic inflammatory response to infection, which can be seen following a wide variety of insults includes multiple trauma/burn, hemorrhagic shock, surgery, ischemia, immune-mediated organ injury. It is the most common cause of death in noncancer disease.With respect to the host's defense against septic challenge, the immune system appears to exhibit a biphasic response. Initially, there appears to be an exaggerated systemic pro-inflammatory response thought to be due to immune cell stimulation by microbes and/or their products. The exacerbation of this pro-inflammatory state is suggested tobe contributor to organ injury. Alternatively, over time, the host frequently enters an immunological state characterized by T cell hyporesponsiveness, anergy, and a defect in antigen presentation. The augmentation of either a sustained pro-inflammatory condition or anti-inflammatory state implicate a loss of regulatory function. One of the central components in the control of immune, inflammatory response is the ability to sustain cells contributing to these responses by regulation of their cellular suicide program (apoptosis). There is rapidly developing evidence to suggest that increased apoptosis may play a determining role in the outcome to sepsis. In particular, increased apoptosis, particularly in lymphoid tissues and some parenchymal tissues from solid organs, may contribute to sepsis-associated MODS and can be a potential therapeutic target for intervention.Lungs and liver act as targets and sources of inflammatory mediators and play the pivotal role in the pathogenesis of sepsis. 3 -defensin 2 is a small molecule anti-microbial peptide located in the epitherium of pulmonary tissue and skin. Recent studies showed that this small peptide is of particular importance against microbial infection either via innate immune response or acquired immune response. It would be helpful to sepsis that clarifying the effect and mechanism of β-defensin 2 on the lungs.ObjectiveSepsis was induced by cecal ligation and puncture (CLP) in rat.Recombinant adenovirus carrying the gene encoding rat P-defensin 2 (Ad-rBD2) was used to achieve the expression of P-defensin 2 peptide. Ad-rBD2 and control adenovirus were administered intratracheally to Sprague-Dawley rats 48h prior to the performance of CLP respectively. The effect of recombinant P-defensin 2 peptide on the pathological alteration and apoptosis in the lung tissue was studied. Furthermore, the protective role of this peptide on sepsis was discussed.Materials and MethodsThirty-six S-D rats were randanly divided into two groups. Contrast group: eighteen rats received 50μl(5×10~5PFU) control adenovirus nonexpression P-defensin 2 (Ad-lacz) through trachea intubation. Study group: eighteen rats received 50μl(5×10~5PFU) recombined adenovirus expression P-defensin 2(Ad-rBD2). All the rats were performed cecal ligation and puncture to induce sepsis 48h after trachea administration. At the time of 12h, 36h and 72h after CLP, the rats were killed and lungs were fixed in 10% buffered formalin for Haematoxylin and Eosin(H&E) stain and TUNEL test(Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling), in 2.5% glutaraldehyde for electronmicroscopic analysis. ResultLight microscopic analysis of lungs (H&E stain) was performed to evaluate pulmonary architecture, tissue edema formation, and infiltration of neutrophil leukocyte. We found that, in the contrast group, interstitial edema with massive infiltration of the inflammatory cell, and the pulmonary architecure was damaged. In the study group, pulmonary architecture was preserved and infiltration of inflammatory cells and edema decreased. Tunel test showed more positive cells in the contrast group. Electron microscope demonstrated characteristic findings of apoptosis, including markedly condensed chromatin with margination, nuclear solidated. The membrane of cells appeared to be intact in most cells.ConclusionIn our study, we found that septic rat undergo apoptosis in lungs.Recombine P-d... |
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