Effects Of Interferon-α On Pancreatic Fibrosis And Expression Of α-Smooth Muscle Actin And Collagen Type Ⅲ In Rats

AimTo investigate the effect of interferon-alpha(IFN-a) injected subcutaneously on the degree of pancreatic fibrosis in rat experimental model induced by intraperitoneally treated diethyldithiocarbamate(DDC) repeatly. To investigate whether IFN-αhas antifibrotic effect on pancreatic fibrosis rat model induced by DDC and its possible mechanism by observing its effects on the expression ofα-SMA and collagen type III in pancreatic tissues.MethodsFourty male Wistar rats weighting 200~250g were divided into three groups randomly: group A (normal controls, n=10) group B (fibrotic model controls, n=15) and group C (IFN-αpreventing group, n=15). Group B and group C were induced by repeated intraperitoneal DDC injection with the dose of 1000mg/kg body weight twice weekly for 6 weeks. Group C were received intraperitoneal injection of the same dose of saline twice weekly. At the same time, group C were treated with subcutaneously injection of IFN-αin saline, administed daily at the doses of 10~5U, the other two groups injected with saline at the same dose. At the end of the sixth week, all the rats were killed, the samples of the pancreas obtained by biopsy were fixed in formaldehycle solutions, embedded in paraffin and stained with H-E and Masson-Trichrome. The expression ofα-SMA and collagen type III in pancreatic tissues were detected with immunohistochemical methods. The image was processed by micro image analysis system.ResultsRepeated administraton of DDC caused inter- and intralobular fibrosis with dilation of intra-acinar lumina in the pancreas. Some acinar cells atrophied and have been replaced by fatty tissues. No histological changes except for some mild haemorrhage and infiltration of inflammatory cells were seen in normal control rats. The degree of fibrosis score in group C was significantly less than that of group B under light microscope (P<0.05). In normal control rats, there is no collagen type III expression in pancreatic parenchyma. DDC injections induced massive collagen deposition mainly located in periacinar areas. Image analysis showed that the quantity of collagen type III protein expression of group C was markly lower than in rats of group B(P<0.05). In normal pancreas,α-SMA staining was seen only around the pancreatic ducts and blood vassels. DDC injections induced the proliferation ofα-SMA-positive activated PSCs in the fibrotic areas, mainly located in the interlobular and periacinar areas. Image analysis showed that the level of pancreaticα-SMA in group C was also significantly less than that of group B (P<0.05).ConclusionThe study showed that both pathological score of pancreatic fibrosis and the level of ECM proteins expression were all ameliorated in IFN-αtreated rats, which indicated that IFN-αcould prevent pancreatic fibrogenesis in experimental rats. The probable mechanisms include IFN-αcan inhibit PSC activation and increase the degradation of collagens through enhancing the activity of collagenasas, which may partly account for the suppressive effect of IFN-αon pancreatic fibrosis. But the exact mechanism remains to be further studied.