Chinese Journal of Tissue Engineering Research ›› 2021, Vol. 25 ›› Issue (17): 2687-2696.doi: 10.3969/j.issn.2095-4344.3138
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Zhou Yi, Chen Yueping, Zhang Xiaoyun, Lai Yu, Liao Jianzhao, Li Shibin
Received:
2020-05-06
Revised:
2020-05-12
Accepted:
2020-06-03
Online:
2021-06-18
Published:
2021-01-08
Contact:
Chen Yueping, MD, Chief physician, Department of Traumatology and Hand Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
About author:
Zhou Yi, Master candidate, Department of Traumatology and Hand Surgery, Ruikang Hospital Affiliated to Guangxi University of Chinese Medicine, Nanning 530011, Guangxi Zhuang Autonomous Region, China
Supported by:
CLC Number:
Zhou Yi, Chen Yueping, Zhang Xiaoyun, Lai Yu, Liao Jianzhao, Li Shibin. An exploration on mechanism of Shengyu Decoction in treating osteonecrosis of the femoral head based on network pharmacology[J]. Chinese Journal of Tissue Engineering Research, 2021, 25(17): 2687-2696.
2.4 构建“活性成分-靶点”和“疾病-药物-活性成分-靶点”网络 运用Cytoscape软件构建“活性成分-靶点”网络,见图3,共包括100个节点(27个活性成分节点和73个靶点节点)和182条边。同时构建“疾病-药物-活性成分-靶点”,见图4。使用Network analyze功能对网络进行拓扑属性分析,其中度值是衡量1个节点在网络中关键性的重要参数。该网络中度值排名前5位的化合物分别是山柰酚 (kaempferol)、槲皮素(quercetin)、β-谷甾醇(beta-sitosterol)、豆甾醇(Stigmasterol)和异鼠李素(isorhamnetin)、分别能与65,45,43,14,10个靶点连接,对治疗股骨头坏死具有重要的意义,其基本信息见表3。 2.4 构建“活性成分-靶点”和“疾病-药物-活性成分-靶点”网络 运用Cytoscape软件构建“活性成分-靶点”网络,见图3,共包括100个节点(27个活性成分节点和73个靶点节点)和182条边。同时构建“疾病-药物-活性成分-靶点”,见图4。使用Network analyze功能对网络进行拓扑属性分析,其中度值是衡量1个节点在网络中关键性的重要参数。该网络中度值排名前5位的化合物分别是山柰酚 (kaempferol)、槲皮素(quercetin)、β-谷甾醇(beta-sitosterol)、豆甾醇(Stigmasterol)和异鼠李素(isorhamnetin)、分别能与65,45,43,14,10个靶点连接,对治疗股骨头坏死具有重要的意义,其基本信息见表3。 2.5 PPI网络及网络拓扑分析结果 通过STRING数据库以最低要求互动得分(minimum required interaction score)为0.7为筛选参数分析共得到233对蛋白互作关系,涉及73个蛋白靶点。采用Cytoscape软件构建蛋白互作网络,见图5。 "
文章通过Network Analyzer工具分析网络中节点的度值,将度值≥8(均值)的靶点由高到低排序,见图6。度值排名前5的蛋白基因是炎性细胞因子白细胞介素6(Interleukin-6,IL-6)、血管内皮生长因子A(Vascular endothelial growth factor A,VEGFA)、原癌基因蛋白(Proto-oncogene proteins,jun)、基质金属肽酶9(Matrix metalloproteinase-9,MMP9)及炎性细胞因子白细胞介素1β(Interleukin-1 beta,IL-1β)。这些蛋白在整个网络中起着关键的作用,蛋白所对应的靶点在圣愈汤治疗治疗股骨头坏死中具有重要作用,认为是圣愈汤治疗股骨头坏死的关键靶点。"
2.6 GO富集分析结果 GO富集分析得到GO条目共804个(P < 0.01),其中生物过程(BP)、细胞组成(CC)和分子功能(MF)条目分别为732,23,49个。 从生物过程的相关条目分析,圣愈汤治疗股骨头坏死的靶点主要参与对炎症反应(Inflammatory reaction)、氧化应激反应(response to oxidative stress)和血管生成调节(regulation of angiogenesis)等过程;从细胞组成的相关条目分析,治疗靶点主要包括转录因子复合体(transcription factor complex)、内质网腔(intrinsic component of postsynaptic)及核染色质(RNA polymerase II transcription factor)等区域;从分子功能的相关条目分子,治疗靶点主要与丝氨酸水解酶活性(serine hydrolase activity)、调节核受体活性(nuclear receptor activity)和蛋白酶结合(protease binding)等方面相关。根据P值排序,每个模块前20位的条目见图7。 "
2.8 分子对接验证 将“2.4”项筛选出的关键化合物和“2.5”项的关键靶蛋白进行分子对接验证。分子对接结果显示圣愈汤关键活性化合物与靶蛋白的分子对接亲和力均远小于-5.0 kJ/mol,结果表明圣愈汤中关键化合物与关键靶蛋白有较好的结合活性,结果见表4。山奈酚为预测靶点最多的活性成分,白细胞介素6为PPI网络中degree值最大的靶点,以山奈酚和白细胞介素6蛋白结构对接模式为例,结果显示山柰酚能稳定地对接到白细胞介素6蛋白结构的活性口袋中,见图9;山奈酚与白细胞介素6蛋白结合关键疏水氨基酸残基是ASP-1042,ARG-01041,GLY-1097,GLN-1098,THR-1100,PHE-1046, MET-1085,VAL-1045和HIS-1096。 "
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