CAJ | 학술논문

背景：胰腺星状细胞内转化生长因子β1/Smads信号通路活化可能是导致胰腺组织纤维化的主要分子学机制。如能阻断这一通路，就可能抑制慢性胰腺炎组织的纤维化进程。目的：探讨秋水仙碱对慢性胰腺炎模型大鼠转化生长因子β1/Smads通路的抑制作用。方法：健康雄性 SD 大鼠随机分为慢性胰腺炎组及秋水仙碱干预组，慢性胰腺炎造模成功后，秋水仙碱干预组大鼠每日腹腔内注射秋水仙碱150μg/ kg，慢性胰腺炎组则每日腹腔内注射等体积的生理盐水。3个月后取胰腺组织，苏木精-伊红染色观察胰腺组织的病理学改变，免疫组化观察胰腺组织转化生长因子β1表达， Western blot法测定胰腺星形细胞内P-Smad2、P-Smad3、α-SMA蛋白表达水平。结果与结论：苏木精-伊红染色结果显示：与秋水仙碱干预组相比，慢性胰腺炎组胰腺组织内腺体组织减少，而纤维结缔组织、炎细胞明显增多并取代胰腺腺体组织。免疫组化结果显示：秋水仙碱干预组胰腺组织内转化生长因子β1阳性表达级别和阳性细胞指数显著低于慢性胰腺炎组(P <0.05)。Western blot结果显示：慢性胰腺炎组胰腺星形细胞内 P-Smad2/β-actin、P-Smad3/β-actin、α-SMA/β-actin 表达明显低于秋水仙碱干预组(P <0.05)。结果提示秋水仙碱可以抑制慢性胰腺炎大鼠转化生长因子β1/Smads信号通路及胰腺组织纤维化。因此，秋水仙碱可作为治疗慢性胰腺炎纤维化的一种新的候选方案。
배경：이선성상세포내전화생장인자β1/Smads신호통로활화가능시도치이선조직섬유화적주요분자학궤제。여능조단저일통로，취가능억제만성이선염조직적섬유화진정。목적：탐토추수선감대만성이선염모형대서전화생장인자β1/Smads통로적억제작용。방법：건강웅성 SD 대서수궤분위만성이선염조급추수선감간예조，만성이선염조모성공후，추수선감간예조대서매일복강내주사추수선감150μg/ kg，만성이선염조칙매일복강내주사등체적적생리염수。3개월후취이선조직，소목정-이홍염색관찰이선조직적병이학개변，면역조화관찰이선조직전화생장인자β1표체， Western blot법측정이선성형세포내P-Smad2、P-Smad3、α-SMA단백표체수평。결과여결론：소목정-이홍염색결과현시：여추수선감간예조상비，만성이선염조이선조직내선체조직감소，이섬유결체조직、염세포명현증다병취대이선선체조직。면역조화결과현시：추수선감간예조이선조직내전화생장인자β1양성표체급별화양성세포지수현저저우만성이선염조(P <0.05)。Western blot결과현시：만성이선염조이선성형세포내 P-Smad2/β-actin、P-Smad3/β-actin、α-SMA/β-actin 표체명현저우추수선감간예조(P <0.05)。결과제시추수선감가이억제만성이선염대서전화생장인자β1/Smads신호통로급이선조직섬유화。인차，추수선감가작위치료만성이선염섬유화적일충신적후선방안。
BACKGROUND:Pancreatic stelate cels transforming growth factor β1/Smads signaling pathway activation is probably a main molecular mechanism of pancreatic fibrosis. If this pathway can be blocked, the progression of fibrosis of tissues with chronic pancreatitis wil be inhibited. OBJECTIVE:To study the inhibitory effect of colchicine on transforming growth factor β1/Smads pathway in chronic pancreatitis rat models. METHODS:Healthy male Sprague-Dawley rats were randomly divided into colchicines-treated group and chronic pancreatitis group. After successful establishment of rat models of chronic pancreatitis, the rats in the colchicines-treated group were intraperitonealy injected with colchicine 150 μg/kg daily. The rats in the chronic pancreatitis group were intraperitonealy injected with equal volume of physiological saline daily. Pancreatic tissues were colected after 3 months. Hematoxylin-eosin staining was used to observe histopathological changes of pancreatic tissue. Immunohistochemical staining was used to detect the expressions of transforming growth factor β1 in pancreatic tissue. Western blot assay was utilized to detect the expressions of P-Smad2, P-Smad3 and α-SMA protein in pancreatic stelate cels. RESULTS AND CONCLUSION: Hematoxylin-eosin staining results revealed that compared with the colchicines-treated group, glandular tissue had reduced, while fibrous connective tissue and inflammatory cels had increased obviously and replaced the pancreatic gland tissue in the chronic pancreatitis group. Immunohistochemical staining results demonstrated that the expression levels of transforming growth factor β1 and the index of positive cels were significantly lower in the colchicines-treated group than those in the chronic pancreatitis group (P < 0.05). Western blot assay results revealed that the results of P-Smad2/β-actin, P-Smad3/β-actin andα-SMA/β-actin in pancreatic stelate cels were significantly lower in the chronic pancreatitis group than those in the colchicines-treated group (P < 0.05). Results suggested that colchicine could inhibit the activity of transforming growth factor β1/Smads pathway and pancreatic tissue fibrosis in chronic pancreatitis rats. Therefore, colchicine can be used as a new candidate therapeutic scheme for chronic pancreatitis fibrosis.