关白附水煎液的抗肿瘤作用机制研究

Anti-tumor Mechanism of Radix Aconiti Coreani Decoction Based on Network Pharmacology

[目的]观察关白附水煎液对小鼠H22肝癌皮下移植瘤的抗肿瘤作用,分析其可能的抗肿瘤作用机制。[方法]建立小鼠H22肝癌皮下移植肿瘤模型。给药组于肿瘤接种后次日,用人体等效日剂量的关白附水煎连续灌胃治疗15 d,1次/d;模型组用等量生理盐水灌胃,作对照。通过小鼠体质量、自主活动、肿瘤体积等评价关白附水煎液对H22肝癌皮下移植瘤小鼠肿瘤生长的抑制作用,用二甲苯诱导的耳肿胀评价关白附对荷瘤小鼠炎症的影响,用伊文思蓝通透性评价关白附对荷瘤小鼠血管通透性的影响,利用网络药理学分析关白附相关靶点和途径。[结果]模型组小鼠体质量显著上升,自主活动下降,耳肿胀严重,血管通透性增加;与模型组相比,给药组小鼠体质量增加减缓,自主活动增加,耳肿胀程度减轻,血管通透性降低,肿瘤抑制率为41.51%(P<0.05)。网络药理学分析结果筛选出16个关白附有效活性成分,PPI网络鉴定了6个核心靶点,涉及47条KEGG通路和45个GO生物过程。[结论]关白附水煎液能够抑制小鼠H22肝癌皮下移植瘤的生长,能减轻荷瘤小鼠炎症和降低血管通透性,其作用与16个关白附活性成分干预"TNF信号通路""NF-ΚB信号通路""Jak-STAT信号通路""癌症中的蛋白多糖"等途径相关。

[Objective]To observe anti-tumor effect of Radix Aconiti Coreani decoction on H22 subcutaneously transplanted tumor in mice,and explore its possible action mechanism.[Methods]A mouse model of H22 subcutaneously transplanted tumor was established,the next day tumor bearing mouse was treated with HED’s Radix Aconiti Coreani decoction via intragastric administration once a day for 15 days.The model group was given normal saline as control.Antitumor effect was evaluated by body weight,autonomic activities,and tumor size.The effect of Radix Aconiti Coreani on inflammation was examined by ear edema in tumor bearing mice,and that of is it the same as Radix Acotini on vascular permeability in tumor-bearing mice by Evans blue permeability,and network pharmacology was used to analyze the related targets and pathways of Radix Aconiti Coreani.[Results]Compared with the control group,the treated mice had slow body weight increase,increased autonomic activities,reduced degree of ear swelling and decreased vascular permiability.Compared with the model group,body weight was increased slowly,autonomic activities was increased,the degree of ear swelling is reduced and reduced vascular permeability in treatment mice,the inhibitory rate of tumor growth was 41.51%(P<0.05).Network pharmacology analysis showed that there are 16 active components in Radix Aconiti Coreani,which target six core targets involving in 47 KEGG pathway and 45 GO bioprocess.[Conclusion]Radix Aconiti Coreani decoction had inhibitory effect on H22 subcutaneously transplanted tumor in mice,could decrease inflammation and vascular permeability in tumor bearing mice,its mechanisms were associated with 16 active components involved in "TNF signaling pathway""NF-kappaB signaling pathway""Jak-STAT signaling pathway" and "Proteoglycans in cancer".