Abstract:Objective:To discuss the effect of anti tumor necrosis factor α(TNF-α) treatment on NF-κB signaling in lung injury in severe acute pancreatitis(SAP) in rats.
Methods :SD rats were randomized into three groups：Control group，SAP group and anti TNF-α antibody treatment group。Each group was divided into 1, 3, 6 and 12 h postoperation subgroups(each,n=6). SAP rat model was induced by intraductal administration of 5% sodium taurocholate. Alveolar macrophages(AM) were obtained by bronchoalveolar lavage. The protein content of bronchoalveolar lavage fluids(BALF), the myeloperoxidase(MPO) of lung tissue and generation of TNF-α by AM were detected. The expression of TNF-αmRNA was measured by RT-PCR technique. The histology of lung was also checked as well as the expression of NF-kappa B was detected by immunohistochemistry.
Results:The activation of NF-kappa B was seldom seen in AM of control group lung tissue, while it could be observed in SAP groups, and NF-kappa B moved from cytoplasm into nuclei with time prolongation.A slight amount of NF-kappa B activation was still observed in anti TNF-α antibody treatment group. The lung injury was increasingly aggravated with disease progression. The level of myeloperoxidase of lung tissue and protein content of BALF were also increased with time prolongation, and the maximum level occurred at 12h［(10.78±0.58) U/g for MPO and (2 011.0±105.5)μg/mL for protein respectively］. The generation of TNF-α by AM was gradually elevated and peaked at 6 h ［（1 624.2±149.2) pg/mL］, but decreased at 12h. The change of expression of TNF-αmRNA was similar to TNF-α. All the indicators of SAP group compared with control group had the statistical significance (P<0.05). All indicators in anti TNF-α antibody treatment group were significalltly increased compared with the control group (P<0.05), however, they were decreased compared with the SAP group (P<0.05). The generation of TNF-α by AM had close relation to the level of MPO of lung tissue and protein content of BALF(r=0.65, 0.76 respectively, P<0.01).
Conclusions:Anti TNF-α antibody treatment could inhibit the feedback effect of TNF-α on the activation of NF-κB of AM, and directly decrease the secretion of TNF-α, which can ameliorate the lung injury in SAP in rats.