Experimental Study On The Signal Transduction Pathway Of Toll-like Receptor 4/Nuclear Factor-κB And The Treatment Effect Of Dahuangfuzi Decoction In Acute Lung Injury With Severe Pancreatitis In Rats

Objective:To investigate the expression of the signal transduction pathway of toll-like receptor 4(TLR4)/ nuclear factor-κB(NF-κB)in severe pancreatitis-acute lung injury ( SP-ALI ) and the role of theropy of Dahuangfuzi decoction.Methods:SD rats weighting 200～250g were randomly divided into four groups: sham opreaion group (Ⅰgroup, n=32), SP-ALI group (Ⅱgroup,n=32), Dahuangfuzi decoction group treatment group (Ⅲgroup,n=32),Xuebijing group(Ⅳgroup,n=32). The model of SP was established by injecting 1ml/kg of 4% sodium tauroeholate in to the pancreatic capsule of the rats inⅡgroup. On the basis of model group,Ⅲgroup andⅣgroup were treated by Dahuangfuzi decoction and Xuebijing 2ml in each group through jejunum stoma tube at 0.5h after modeling. 8 rats of each group being killed in the following 3, 6, 12, 24h. Blood was got from heart to detect serum amylases, determine serum levels of lipopolysaccharide.The histopathologic changes in lung and pancreas were severed. The expression of TLR4, NF-κBp65 in the lungs were detected by immunohistochemistry and western blot after the rats were sacrificed in each time points.Results:⑴Serum amylase, pathologic scores of pancreas and lung ofⅡgroup were significantly higher than those ofⅠgroup 3～24 hours after sodium taurocholate induction ( P <0.05 ) .The pathomorphological obsevation showed the superficies of pancreas inⅡgroup were congestion in 3h after modeling, mild swelling were detected in lungs 3h after modeling; superficies of pancreas and lung were swelling in 6h; necrosis and many saponifying spot were observed in pancreas 12 and 24h, swelling were obviously observed in lung 12 and 24h,and also found lamellar hemorrhage and congestion. The results proved that models of SP-ALI were established successfully.⑵The expression of TLR4 and NF-κB p65 in the lung were significantly higher than that ofⅠgroup with immunohistochemistry and western blot(P <0.05);There were significant positive correlation between the expression of TLR4 and NF-κB p65 (r=0.992,P <0.01) in lung tissue.⑶The serum concentration of lipopoly- saccharide(LPS) and serum amylases inⅢgroup was obviously decreased comparing withⅡgroup 3~24h after operation(P <0.05);The expression of TLR4 and NF-κB p65 in the lung ofⅢgroup were significantly lower than that ofⅡgroup(P <0.05); The expression of TLR4 and NF-κB p65 in the lung and the serum concentration of LPS , serum amylases inⅢgroup were significantly lower than them inⅣgroup(P <0.05).Conclusions:⑴The models of SP-ALI were established successfully by injecting 1ml/kg of 4% sodium taurocholate into the pancreatic duct.⑵Signal transduction pathway of TLR4/NF-κB were involved in the pathogenesis of SP-ALI.⑶Dahuangfuzi decoction can significantly reduce the level of LPS,inhibit the expression of TLR4 and NF-κB p65 in lung tissue,and decrease the expression of TNF-α, IL-1βin lung tissue, reduce the degree of SP-ALI at last; the prevention effect of Dahuangfuzi decoction is more better than that of Xuebijing.