干扰素α干预对大鼠胰腺纤维化的影响

Interferon-alpha treatment for pancreatic fibrosis in rats

目的 观察干扰素α(INF-α)对DDC诱导的胰腺纤维化大鼠模型纤维增生程度、胰腺星状细胞活化标志物α-平滑肌肌动蛋白(α-SMA)和细胞外基质成分Ⅲ型胶原蛋白表达的影响.方法 Wistar大鼠40只随机数字法分成对照组、纤维化组和干扰素组.纤维化组和干扰素组每周2次腹腔内注射DDC,干扰素组在造模同时每天皮下注射INF-α10万U.6周末取材,光镜下观察胰腺病理学变化.免疫组化法测定胰腺组织中α-SMA、Ⅲ型胶原蛋白的表达.结果 第4周起纤维化组大鼠体重增长缓慢甚至下降,干扰素组体重仍缓慢增长,5周后两组差异显著[(309.8±19.7)g与(277.3±19.9)g,P＜0.05].纤维化组胰腺组织纤维化表现明显,纤维化分值、Masson染色值、α-SMA和Ⅲ型胶原蛋白相对表达量分别为2.679±0.899、218.713±36.102、148.971±30.686和88.142±42.581;干扰素组纤维化减轻,上述指标分别为1.952±0.219、114.732±24.912、77.237±9.275和59.952±25.498,均较纤维化组显著降低(P＜0.05).结论 给予INF-α能显著减轻纤维化程度和α-SMA、Ⅲ型胶原表达,对DDC诱导的大鼠胰腺纤维化有一定的预防作用.

Objective To investigate the effect of interferon-alpha (IFN-α) on preventing pancreatic fibrosis and expression of pancreatic α-smooth muscle actin (α-SMA) and collagen type m in experimental rat model induced by diethyldithiocarbamate (DDC). Methods Forty male Wistar rats were randomly divided into three groups: normal control group, fibrotic group(PF group) and IFN-α prevention group(IFN-α group). Pancreatic fibrosis were induced by repeated intraperitoneal DDC injection. IFN-α group were treated with subcutaneous injection of IFN-α in saline, administered daily at the dosage of 105 U. Six weeks later, all the rats were sacrificed, the samples of the pancreatic tissue obtained by biopsy were submitted to histological studies. The expression of α-SMA and collagen type Ⅲ in pancreatic tissues were detected by immunohistochemistry. Results From the 4th week on, the weight of rats in PF group grew slowly, some rats 'weight even decreased, while the weight of rats in IFN-α group kept growing up slowiy, and the difference became significant at the 5th week (306.17±20.89 g vs 279.17±23.58 g, P＜0.05 ). The fibrosis score, Masson stain score, α-SMA and pancreatic collagen type Ⅲ in PF group were 2.679±0.899, 218. 713± 36. 102, 148.971±30. 686 and 88. 142±42.581, respectively, and the corresponding values in PF group were 1.952±0.219, 114.732±24.912, 77.237±9.275 and 59.952±25.498, respectively. The extent of fibrosis in IFN-α group was significantly better than that in PF group (P＜0.05). Conclusions IFN-α may inhibit the extent of fibrosis, decrease the expression of α-SMA and pancreatic collagen type Ⅲ, therefore, it may partially prevent pancreatic fibrosis induced by DDC.