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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 ,具体机制可能与NFκB表达增加并活化有关
Objective: To investigate the role of NF-κB in angiotensin II-mediated pancreatic fibrosis in rats. Methods: SD rats (200-30O g) were randomly divided into normal group, control group and treatment group. Rat pancreatic duct retrograde injection of 2% trinitrobenzene sulfonic acid (TNBS) into pancreatic fibrosis model. The rats in the treatment group were given Losartan (10 mg · kg-1 · d-1) orally, and the model group was given the same amount of sterile distilled water. The expression, distribution and activation of NF-κB in pancreatic tissue were detected by Western blot, immunohistochemistry and TransAMTM respectively. The number, distribution and activation of mast cells were observed by toluidineblue staining and transmission electron microscopy. RT-PCR was used to study the expression of intercellular adhesion molecule-1 (ICAM-1) in pancreatic tissue. Results: The expression and activity of NF-κB p65 protein in the pancreas tissue of the 3rd day after model establishment increased and peaked on the 7th day [(0 406 ± 0 866 mg / g total protein)]. The mast cells were activated in the pancreas of the control group; the expression of ICAM - 1 mRNA increased on the 3rd and 7th day. Losartan can inhibit NF-κB protein expression and mast cell activation, down-regulated ICAM-1 mRNA expression. CONCLUSION: Angiotensin II may induce inflammation and fibrosis through the receptor AT1 pathway in the early stage of rat pancreatic fibrosis. The specific mechanism may be related to the increase and activation of NFκB