IFN-α对大鼠胰腺纤维化组织中Smad7及PDGF-B表达的影响

Effects of interferon-alpha on the expression of Smad7 and PDGF-B in fibrotic pancreas in rats

目的:观察Smad7和PDGF-B在纤维化胰腺组织中的表达及应用干扰素-α(IFN-α)对二者表达的影响.方法:312只雌性Wistar大鼠,随机分成对照组、纤维化组和干扰素组.每周向纤维化组和干扰素组大鼠腹腔内注射2次二乙基二硫代氨基甲酸盐(diethyldithiocarbamate,DDC)造模;干扰素组于造模同时每天皮下注射IFN-α10万单位.纤维化组分别于0,1,2,3,4,6,8wk末取材,干扰素组于6wk末取材,应用免疫组织化学法测定纤维化胰腺组织中Smad7、PDGF-B的表达.结果:与对照组相比,Smad7表达于纤维化第3周开始减少(34.22±7.60vs53.46±30.45P<0.01),3-8wk末呈低表达.PDGF-B表达从纤维化开始即呈高表达(均P<0.01),随时间的延长,PDGF-B表达逐渐增加,造模8wk末PDGF-B下降.干扰素组6wk末Smad7的表达较同期纤维化组增加(47.22±17.26vs15.27±9.65,P<0.01);PDGF-B表达明显减少(29.13±11.06vs57.63±40.66,P<0.01),其表达同纤维化组3wk末.结论:干扰素的应用可以降低PDGF-B的表达,增高Smad7的表达.

AIM：To investigate the effects of interferonalpha（IFN-α）on the expression of Smad7 and PDGF-B in fibrotic pancreas in rats with diethyldithiocarbamate（DDC）-induced pancreatic fibrosis. METHODS：Three hundreds and twelve female Wistar rats were randomly divided into three groups：normal control group,model control group and IFN-αtreatment group.Rats in the model control group and IFN-αtreatment group were given repeated intraperitoneal injections of DDC to induce pancreatic fibrosis.Meanwhile,a subcutaneous injection of IFN-αwas given to rats in the IFN-α treatment. The rats in the model control group were sacrificed at weeks 0, 1, 2, 4, 6 and 8 after initial induction with DDC, respectively, to take samples, while those in the IFN-α treatment group were sacrificed at week 6. The expression of Smad7 and PDGF-B in fibrotic pancreas were detected by immunohistochemistry.RESULTS： Compared with the normal control group, the expression of Smad7 in the model control group began to decrease from week 3 （34.22 ± 7.60 vs 53.46 ± 30.45, P 〈 0.01） and was kept at low level from weeks 3 to 8, while the expression of PDGF-B in the model control group was high at the beginning （P 〈 0.01）, gradually increased from weeks 3 to 7, and began to decrease from week 8. The expression level of Smad 7 at week 6 in the IFN-α treatment group was significantly higher than that in the model control group （47.22 ± 17.26 vs 15.27 ±9.65, P 〈 0.01）. In contrast, the expression level of PDGF-B at week 6 in the IFN-α treatment group was significantly lower than that in the model control group （29.13 ± 11.06 vs 57.63 ± 40.66, P 〈 0.01）. CONCLUSION： IFN-α is able to inhibit the expression of PDGF-B but promote the expression of Smad7 in fibrotic pancreas in rats.