己酮可可碱对大鼠胰腺纤维化及TGF-β1、α-SMA、MMP-1、TIMP-1表达的影响

Effect of pentoxifylline on the expressions of TGF-β 1,α-SMA,MMP-1 and TIMP-1 in rat pancreatic fibrosis

目的探讨己酮可可碱(PTX)对大鼠胰腺纤维化及TGF-β1、α-SMA、MMP-1、TIMP-1表达的影响。方法通过胰管内注射2%三硝基苯磺酸的方法制备大鼠胰腺纤维化模型。随机分为对照组、模型组、PTX干预组。PTX干预组于术后第2天给予PTX腹腔注射,6mg/(kg·d),4周后收集各组胰腺标本。免疫组化SABC法检测各组胰腺组织中α-平滑肌肌动蛋白(α-SMA)、转化生长因子β1(TGF-β1)、基质金属蛋白酶-1(MMP-1)、金属蛋白酶组织抑制物-1(TIMP-1)的表达同时做组织胶原纤维染色。部分胰腺组织液氮冻存,以Westernblot方法检测α-SMA的表达。结果模型组发生胰腺纤维化,PTX干预组有轻度纤维化。PTX干预组α-SMA、TGF-β1、TIMP-1的表达均低于模型组(P<0.01)。MMP-1的表达无明显差异。PTX干预组胶原面积百分比明显低于模型组(P<0.01)。结论PTX抗大鼠胰腺纤维化的作用可能与其降低TGF-β1、α-SMA、TIMP-1表达有关。

Objective ：To observe the effect of pentoxifylline on pancreatic fibrosis and the expressions of TGF-β1,α-SMA,MMP-1 and T IMP-1 in rat. Methods ：The injection method of 2% TNBS through rats＇s pancreatic duct was undertaken to set up the animal model of pancreatitis, Mice of interventional group were treated with PTX,and the samples of pancreas were collected after 4 weeks treatment for evaluating the expression of TGF-β1,α-SMA,MMP-1 and TIMP-1 by using Immunohistochemistry technique. Masson staining of pancreas were undertaken. The expression of α-SMA in some samples were evaluated by using Western blot. Results ： Pancreas fibrosis was observed in model group rats and there were no significant pancreas fibrosis in PTX interventional group. PTX interventional significantly reduced the content of TGF-β1,α-SMA, and TIMP-1 compared to the model（P〈0. 01）,while that of MMP-1 was unchanged in PTX interventional group. Pancreas fibrosis proportion was also reduced in PTX interventional group （P〈0.01）. Conclusion： PTX could inhibit the formation of pancreas fibrosis in rats, which might relate to the decreasing expression of TGF-β1,α-SMA, TIMP-1.