关键词:  , 慢性胰腺炎, 脂多糖, 内毒素血症, TLR4信号通路, 应答基因

Abstract:

Objective To detect  the expression of key factors of toll-like receptor 4 (TLR4) signaling pathway in pancreas and serum of the patients with chronic pancreatitis(CP), and to explore the significance of TLR4 signaling pathway in the occurrence and development of CP. Methods Pancreas tissues from 24 patients with CP and 6 controls with normal pancreatic histology were  collected to detect TLR4 mRNA by in situ hybridization. The MyD88 and TNF-ɑ were detected by immunohistochemistry. Computer iag nalysis was performed to measure integrated optimal density (IA) of TLR4 mRNA, MyD88 and  TNF-ɑ in pancreas sections. The fasting vein blood samples were collected in 84 patients with CP and 30 normal individuals. The serum soluble TLR4 (sTLR4), TNF-ɑ,  IL-6 and IL-12 levels were measured by ELISA. The lipopolysaccharide (LPS) level in plasma was determined by spectrophotometry. The relationships between the plasma PLS level and different cytokines were analyzed. Results In situ 　hybridization analysis showed that the expression levels of TLR4 mRNA, MyD88 and TNF-ɑ in the pancreas tissue of the CP patients were significantly higher than those in  normal control group(P<0.01),and they were 4.2-fold, 6.1-fold and 10.2-fold of the normal controls. The blood LPS, sTLR4, TNF-ɑ, IL-6, and IL-12 levels in the CP patients were significantly increased compared with normal control group(P<0.05 or P<0.01). Bivariate correlation analysis showed that there were significantly positive correlations between the level of plasma LPS and the levels of serum TNF-α, IL-6 and IL-12 in the patients with endotoxemic CP (r=0.859,P<0.01; r=0.688, P<0.01; r=0.539, P<0.05). Conclusion LPS-TLR4 signaling pathway and their response gene products in pancreas tissue and peripheral blood of the   CP patients are up-regulated，and it plays an important role in acute attack stage and inflammation progression of CP.