中国临床药理学与治疗学2018,Vol.23Issue(10):1088-1096,9.DOI:10.12092/j.issn.1009-2501.2018.10.002
益脾养胃汤治疗溃疡性结肠炎相关癌变小鼠的疗效及其机制研究
Therapeutic effect and mechanism of Yipi Yangwei decoction in trea-ting ulcerative colitis-related cancerous mice
摘要
Abstract
AIM: To observe the therapeutic effect of Yipi Yangwei decoction in treating ulcera-tive 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 decoc-tion. 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 corre-sponding dosage of Yipi Yangwei decoction was giv-en to the models at the same time. The general con-dition, colon crypt changes, and colon histopatholo-gy changes of the mice in each group were observed. ELISA method was used to detect the levels of in-flammatory cytokines IFN-γ, IL-4 and IL-12 in ser-um 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 dam- age 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 ex-pression 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 de-creased significantly, and the levels of any other ele-ments 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.关键词
溃疡性结肠炎相关癌变/益脾养胃汤/TLR4/MAPKSKey words
carcinogenesis associated with ul-cerative colitis/Yipi Yangwei decoction/TLR4/MAPKS分类
医药卫生引用本文复制引用
娄朝胜,吴贤,王海波,张寅,叶乐驰..益脾养胃汤治疗溃疡性结肠炎相关癌变小鼠的疗效及其机制研究[J].中国临床药理学与治疗学,2018,23(10):1088-1096,9.基金项目
浙江省自然科学基金资助项目(LY15H160058) (LY15H160058)