关键词: 溃疡性结肠炎相关癌变, 益脾养胃汤, TLR4, MAPKS

Abstract:

AIM: To observe the therapeutic effect of Yipi Yangwei decoction in treating ulcerative colitis-related cancerous mice and its effect on toll-like receptor 4/mitogen-activated protein kinase (TLR4/MAPKS) signaling pathway. METHODS: Eighty BALB/c male mice were randomly divided into the normal group, the model group, the high-dose and low-dose groups of Yipi Yangwei decoction. Each group contains 20 cases. AOM/DSS (azoxymethane/dextran sodium sulfate) method was used to establish murine mouse models of ulcerative colitis-associated cancer. After modeling, the corresponding dosage of Yipi Yangwei decoction was given to the models at the same time. The general condition, colon crypt changes, and colon histopathology changes of the mice in each group were observed. ELISA method was used to detect the levels of inflammatory cytokines IFN-γ, IL-4 and IL-12 in serum of each group. Real-time PCR was used to detect the expression of IFN-γ, IL-4, IL-12 and NF-κBp65 mRNA. The relative expression levels of TLR4, p-JNK1/2 and p proteins were detected by Western blot. RESULTS:Compared with the model group, the body mass and colon length of the mice in each medication administration group were significantly increased, while the colon weight, colon weight length ratio, and colonic mucosal histological damage score were remarkably decreased; the levels of serum IFN-γ and IL-12, as well as the expression levels of IFN-γ and IL-12 mRNA in colon tissues were all significantly decreased, while IL-4 level was significantly increased; the mRNA and protein expression levels of TLR4, p-JNK1/2, p-p38 and p-ERK1/2 in colon tissues and the protein expression levels of p-NF-κBp65, PCNA, COX-2, Bcl-xl were significantly decreased (P<0.05). Compared with the low-dose group of Yipi Yangwei decoction, the histological injury score of colonic mucosa in the high-dose group of Yipi Yangwei decoction decreased significantly, and the levels of any other elements were all higher (P<0.05). The difference of protein expression levels of p-NF-κB(p65) in all groups was without statistical significance（P＞0.05）. CONCLUSION: Yipi Yangwei decoction can relieve the inflammatory injury of colonic mucosa and reduce the risk of cancer. The mechanism may be related to the down-regulation of TLR4/MAPKS signaling pathway.

Key words: carcinogenesis associated with ulcerative colitis, Yipi Yangwei decoction, TLR4, MAPKS