Inhibitory effect of colchicine on transforming growth factor β1/Smads pathway in rat models of chronic pancreatitis
10.3969/j.issn.2095-4344.2014.49.023
- VernacularTitle:慢性胰腺炎模型大鼠转化生长因子β1/Smads通路被秋水仙碱的抑制
- Author:
Hongwei LU
;
Yafei ZHANG
;
Hong JI
;
Jinlong WANG
;
Yiming LI
- Publication Type:Journal Article
- Keywords:
transforming growth factor beta 1;
smad2 protein;
smad3 protein;
pancreatitis,chronic
- From:
Chinese Journal of Tissue Engineering Research
2014;(49):8001-8006
- CountryChina
- Language:Chinese
-
Abstract:
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.
