Roles of nuclear factor-?B in the development of rat pancreatic fibrosis mediated by angiotensin II / 中国病理生理杂志

ABSTRACT

AIM: To determine the effects of NF-?B on the development of rat pancreatic fibrosis mediated by angiotensin II. METHODS: Spraque-Dawley rats (200-300g) were randomly divided into normal group, control group and losartan-treatment group. Pancreatic fibrosis was induced by injection of 2% TNBS into biliopancreatic duct. Rats in losartan-treatment group and control group were respectively treated with losartan (10 mg?kg~(-1)?d~(-1)) by gavage and the same volume of saline vehicle. The expression, distribution, and activation of NF-?B were studied by Western blot, immunohistochemistry and TransAM~(TM). Toluidine blue staining and transmission electron microscopy were also used to observe the number, distribution and degranulation of mast cells. In addition, RT-PCR was performed to detect the intrapancreatic ICAM-1 mRNA expression. RESULTS: The expression and activity of intrapancreatic NF-?B p65 protein were significantly increased on day 3 after operation, reaching peak on day 7 [(0.406?0.086) mg/g total protein]. Mast cell activation was observed and ICAM-1 mRNA levels on day 3 and 7 were up-regulated in control group. Losartan treatment inhibited NF-?B expression and activation, reduced mast cell infiltration and degranulation and decreased ICAM-1 mRNA expression compared with control rats. CONCLUSION: It might be associated with the expression and activation of NF-?B that angiotensin II mediates inflammation and fibrosis in the early stage of pancreatic fibrosis. [