Effect of TLR4/NF-κBp65 Signaling Pathway on Acute Kidney Injury of Rats With Severe Acute Pancreatitis / 胃肠病学

ABSTRACT

Background:TLR4/NF-κBp65 signaling pathway plays an important role in triggering inflammatory response,and regulates releasing of cytokines in acute pancreatitis. However,the role of this pathway in inflammation in severe acute pancreatitis(SAP)associated with acute kidney injury(AKI)is not clear. Aims:To investigate the effect of TLR4/NF-κBp65 signaling pathway on AKI in experimental SAP. Methods:Thirty-two male Sprague-Dawley rats were randomly assigned into 4 groups(8 each)normal control group,SAP 6 h,12 h,and 18 h groups. SAP was induced by retrograde injection of 4% sodium taurocholate into biliopancreatic duct. Serum levels of creatinine(Cr)and blood urea nitrogen (BUN)were measured dynamically. Pathological changes of kidney were observed macro- and microscopically. Serum levels of tumor necrosis factor-α(TNF-α)and interleukin-6(IL-6)were determined by ELISA,and the localization and expressions of TLR4 and NF-κBp65 in kidney were determined by immunohistochemical staining and Western blotting. Results:Compared with normal control group,the kidney injuries in SAP groups were gradually aggravated with disease progression;meanwhile,serum levels of Cr,BUN,TNF-α and IL-6 increased significantly,and the expressions of TLR4 and NF-κBp65 in kidney became more intensive(P all <0.05). Expressions of TLR4 and NF-κBp65 in kidney were positively correlated with the serum levels of Cr,BUN,TNF-α and IL-6. Conclusions:In experimental SAP,the changes of TLR4 and NF-κBp65 expressions in kidney are coincidence with the severity of kidney injury and the serum levels of proinflammatory cytokines,which indicates that TLR4/NF-κBp65 signaling pathway plays an important proinflammatory effect in disease progression of SAP associated with AKI.