Sodium Butyrate Ameliorates Intestinal Injury and Improves Survival in a Rat Model of Cecal Ligation and Puncture-Induced Sepsis

Sepsis is a life-threatening condition with a high rate of mortality. Unfortunately, very few therapies can improve outcomes in patients with sepsis. Butyrate, which is the most potent histone deacetylase (HDAC) inhibitor among short-chain fatty acids, exerts anti-inflammatory effects in a variety of inflammatory diseases. Butyrate might thus be valuable in the treatment of sepsis, in which inhibition of overwhelming cytokine release is vitally important. Sepsis was induced in 7- to 8-week-old Sprague-Dawley rats by cecal ligation and puncture (CLP) with a 21-g double-puncture technique. Rats received an intravenous injection of normal saline (vehicle) or sodium butyrate (200 mg/kg) after CLP and were sacrificed 12 h later. Hematoxylin and eosin staining was performed to observe the intestinal mucosal morphology. RT-PCR and ELISA were used to determine the intestinal inflammatory response in vivo. Intestinal permeability was evaluated by measuring fluorescein isothiocyanate dextran (FD-4) absorption in vivo, and tight junction protein expression was examined by western blot. NF-κB p65 activities were assessed by western blot and immunohistochemistry. Sodium butyrate treatment improved the survival rate of CLP rats and alleviated sepsis-induced intestinal mucosal injury. Proinflammatory cytokine expression was lower in butyrate-treated rats than in the vehicle group. FD-4 leakage from the intestinal tract was reduced, and the expression levels of the tight junction proteins claudin-1 and ZO-1 were also restored in rats that received sodium butyrate treatment. These effects were associated with less NF-κB p65 nuclear translocation, whereas the expression of Iκ-Bα was not affected or even increased. Sodium butyrate mitigates the inflammatory response and maintains intestinal barrier function in polymicrobial sepsis partly through inhibition of NF-κB activation and may serve as a novel therapy for sepsis.