摘要
目的 :探讨NF -κB在血管紧张素II介导的大鼠胰腺纤维化发生中的作用。方法 :SD大鼠 (2 0 0 -30 0g)随机分为正常组、对照组、治疗组。大鼠胰管内逆行注射 2 %三硝基苯磺酸 (TNBS)复制胰腺纤维化模型。于造模后第 1d始 ,治疗组给予洛沙坦灌胃 (10mg·kg-1·d-1) ,模型组给予等量的无菌蒸馏水。分别采用免疫印迹、免疫组化和TransAMTM方法检测胰腺组织NF -κB表达、分布和活化情况。采用硫堇蓝 (toluidineblue)染色和透射电镜观察肥大细胞数量、分布和活化脱颗粒现象。RT -PCR研究胰腺组织细胞间粘附分子 (ICAM - 1)mRNA表达。结果 :造模后第 3d大鼠胰腺组织NF -κBp6 5蛋白表达及其活性增加 ,第 7d达峰值 [(0 4 0 6± 0 0 86 )mg/g总蛋白 ]。对照组大鼠胰腺组织中肥大细胞活化 ;ICAM - 1mRNA表达于第 3d和第 7d增加。洛沙坦可抑制NF -κB蛋白表达和肥大细胞活化、下调ICAM - 1mRNA表达。结论 :血管紧张素II在大鼠胰腺纤维化形成早期可能通过受体AT1途径促发炎症反应及纤维化 。
AIM: To determine the effects of NF-κB 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-κB 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-κB 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-κB 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-κB that angiotensin II mediates inflammation and fibrosis in the early stage of pancreatic fibrosis. [
出处
《中国病理生理杂志》
CAS
CSCD
北大核心
2004年第11期1972-1976,共5页
Chinese Journal of Pathophysiology
基金
上海市科技发展基金资助项目 (No .0 14 1190 6 5 )
