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Sichuan Da Xue Xue Bao Yi Xue Ban ; 39(3): 364-7, 2008 May.
Article in Chinese | MEDLINE | ID: mdl-18575316

ABSTRACT

OBJECTIVE: To elucidate the role of PI3K/Akt in the pathogenesis of UC patients and DSS-induced colitis model in mice. METHODS: (1) The mucosa biopsy specimens were collected from 40 patients with ulcerative colitis, and normal mucosa from 20 colon cancer cases served as control. Effects of wortmannin on expression of TNF-alpha in intestinal mucosal specimens from patients with ulcerative colitis were determined on the condition of tissue culture. (2) Thirty six Balb/c mice were divided randomly into four groups: normal control group, DSS-induced colitis group, DMSO control group and wortmannin treatment group. Colitis was induced by feeding 5% DSS in mice. Disease activity index (DAI) was evaluated and the level of TNF-alpha was measured by ELISA. RESULTS: (1) The TNF-alpha level of intestinal mucosa in wortmannin treatment group was significantly lower than that in UC group (P < 0.05). (2) The DAI scores and TNF-alpha levels were lower significantly in wortmannin treatment group compared with DSS group and DMSO group (P < 0.05), and were higher than those of normal control group (P < 0.05). There were no significance between DSS group and DMSO group (P > 0.05). CONCLUSIONS: PI3K/Akt signal transduction pathway participates in the expression regulation of pro-inflammatory cytokine TNF-alpha. Wortmannin can inhibit PI3K/Akt signal transduction pathway.


Subject(s)
Colitis, Ulcerative/physiopathology , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction/physiology , Adult , Androstadienes/pharmacology , Animals , Colitis, Ulcerative/enzymology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Intestinal Mucosa/drug effects , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Male , Mice , Mice, Inbred BALB C , Middle Aged , Phosphoinositide-3 Kinase Inhibitors , Protein Kinase Inhibitors/pharmacology , Random Allocation , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/biosynthesis , Wortmannin
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