殺菌／通透性增加蛋白對膿毒症大鼠組織TNF-α表達的影響及意義

Objective To evaluate the effect of recombinant bactericidal/permeability increasing protein (BPI) on tissue tumor necrosis factor-α (TNF-α) expression and multiple organ dysfunction in septic rats. Methods Wistar rats were subjected to sepsis induced by cecal ligation and puncture (CLP), and animals were randomly divided into normal controls (n=10), septic group (n=20), and BPI-treated group (n=20). Animals were sacrificed at 12 and 24 hours after CLP. Tissue TNF-α mRNA expression and protein levels in liver, lungs, as well as kidneys were measured at various intervals. Serum alanine aminotransferase (ALT) and creatinine (Cr) levels, and pulmonary myeloperoxidase (MPO) activities were also determined. Results TNF-α mRNA expression levels in liver, lungs, as well as kidneys were markedly increased at 12 hours post-CLP, being 2.46-fold (P＜0.05), 2.86-fold (P＜0.01), and 2.27-fold (P＜0.01) of baseline values, respectively. Meanwhile, TNF-α protein levels in various tissues were significantly elevated compared to normal controls (all P＜0.01). In the BPI-treated group, however, TNF-α mRNA expression in liver, lungs, and kidneys were markedly down-regulated at 12 hours (P＜0.05), together with significant decreases in local TNF-α protein levels and recovery to normal range (P＜0.05). In addition, serum ALT as well as Cr levels at 12 hours, and pulmonary MPO activities at 24 hours in the septic group were much lower than those in the BPI-treated group (P＜0.01). Conclusion Early treatment with BPI could markedly inhibit TNF-α synthesis and release in vital organs, thereby preventing the development of excessive inflammatory response and subsequent multiple organ dysfunction syndrome associated with CLP-induced sepsis.