基于VEGFA、MMP9表达调控的犀角地黄汤抑制血管生成治疗银屑病机制研究

Study on the mechanism of inhibition of angiogenesis by Rhizoma Dihuang Tang based on the regulation of VEGFA and MMP9 expression in the treatment of psoriasis

目的:探讨犀角地黄汤(Xijiao Dihuang Decoction,XJDHD)对银屑病样模型小鼠的治疗效果及血管生成的影响。方法:采用咪喹莫特乳膏(imiquimod cream,IMQ)诱导构建银屑病样小鼠模型,验证XJDHD对皮损的改善作用;皮肤血管分布和迂曲变化评价药物对血管生成的影响。通过数据库收集药物作用靶点和疾病靶点,构建蛋白-蛋白互作网络并筛选核心作用靶点,数据集GSE13355验证核心靶点的差异表达。苏木精-伊红(hematoxylin-eosin staining,HE)染色实验观察皮损部位病理变化;q-PCR法检测血管内皮生长因子A(vascular endothelial growth factor A,Vegfa)和基质金属蛋白酶-9(matrix metallopeptidase 9,Mmp9)mRNA表达变化;酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)检测肿瘤坏死因子α(tumor necrosis factorα,TNF-α)和细胞白介素17(interleukin 17,IL-17)分泌水平的变化。结果:XJDHD能改善模型小鼠的银屑病样症状,并抑制新生血管数量及血管迂曲。网络药理学分析筛选出8个核心靶点,与血管生成相关的VEGFA和MMP9在正常和皮损组织中差异表达。与模型相比,XJDHD能显著下调Vegfa和Mmp9 mRNA的表达水平,显著降低IL-17和TNF-α的含量。结论:XJDHD通过抑制皮损部位血管生产,改善银屑病样皮损症状。

OBJECTIVE To examine the effect of Xijiao Dihuang Decoction(XJDHD)on psoriatic lesions and theangiogenesis-promoting factors level.METHODS A psoriasis-like mouse model was constructed with imiquimod cream,and to evaluate the ameliorative of drugs on psoriasis-like lesions.The distribution and tortuosity of blood vessels at the lesion site were assessed to assess the drug's effect on angiogenesis.XJDHD targets and psoriasis disease targets were collected through databases,and protein-protein interaction networks were constructed,and the core targets were screen out.The differential expression of the core targets was verified by the verification dataset GSE13355.The pathological changes in the skin lesion sitewere observed by Hematoxylin-eosin(HE)staining.The mRNA expression of vascular endothelial growth factor A(VEGFA)and matrix metalloproteinase-9(MMP9)were detectedby q-PCR.Enzyme-linked immunosorbent assay(ELISA)was used to evaluate the effect of drugs on levels of cytokines tumor necrosis factorα(TNF-α)and interleukin 17(IL-17).RESULTS XJDHD improved the symptoms of skin lesions and epidermal thickness in psoriasis-like model mice,and also inhibited the number of neovascularization and vascular tortuosity in the skin of model mice.Through network pharmacology analysis,a total of 8 core targets were screened,and the expression of VEGFA and MMP9 associated with angiogenesis in normal tissues and skin lesions was significantly different.Compared with the model,XJDHD significantly downregulated the mRNA expression of Vegfa and Mmp9 and significantly decreased the levels of IL-17 and TNF-α.CONCLUSION XJDHD functions to improve psoriasis-like lesions by inhibiting the number of neovascularization and vascular tortuosity.