Protective effect of adenoviral transfer of heme oxygenase-1 gene on rats with severe acute pancreatitis.
It is widely accepted that the pathophysiological mechanism of severe acute pancreatitis (SAP) is characterized by the systemic inflammatory response, which eventually causes systemic inflammatory response syndrome (SIRS), multiple organ dysfunction syndrome (MODS), and even death. Heme oxygenase (HO)-1 has been proved to exert anti-inflammatory benefit in a variety of inflammatory diseases, and a variety of methods by which HO-1 overexpression can be induced have been reported. In this study, we hypothesized that transfer of HO-1 gene by adenoviral vector could inhibit the systemic inflammation and the development of MODS. Sprague-Dawley (SD) rats were used as subjects in this study. Each was made into SAP model by retrograded injection through pancreatic duct with 5% sodium taurocholate (0.1 mL/100 g). Normal saline (1 mL/animal) or adenoviral HO-1 gene (Adv-HO-1, 2.0 × 10 PFU/mL/animal) or adenoviral empty vectors (Adv-0, 2.0 × 10 PFU/mL/animal) were injected intraperitoneally. HO-1 expression in serum and tissues including pancreas, liver and kidney was measured and observed to be upregulated in the rats treated with Adv-HO-1. The administration of Adv-HO-1 also inhibited the expression of tumor necrosis factor (TNF)-α and boosted the expression of interleukin-10 (IL-10). The decreasing serum concentration of ALT, AST, BUN and CREA, the amelioration of histopathologic damage in pancreas, liver and kidney tissues, the improvement of survival rate were all observed in rats treated with Adv-HO-1 comparing to others. As a result, this study showed that Adv-HO-1 could exert protective effect including anti-inflammation and organ protection through enhancing the expression of HO-1 in SAP.
Departments of Emergency Intensive Care Unit (FZ, BZ, EC, EM), and Surgery (JF), Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Feihu
F
Zhang
Jian
J
Fei
Bing
B
Zhao
Erzhen
E
Chen
Enqiang
E
Mao
D000256:Adenoviridae / Q000235:genetics*; D000818:Animals; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000008:administration & dosage* / Q000235:genetics / Q000627:therapeutic use; D051547:Heme Oxygenase-1 / Q000008:administration & dosage* / Q000235:genetics; D008297:Male; D010195:Pancreatitis / Q000201:enzymology / Q000235:genetics / Q000517:prevention & control*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000096:biosynthesis / Q000235:genetics; D012720:Severity of Illness Index
D011994:Recombinant Proteins; D051547:Heme Oxygenase-1