Chinese Journal of Tissue Engineering Research ›› 2024, Vol. 28 ›› Issue (2): 193-199.doi: 10.12307/2023.996
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Liu Baofang1, Xu Bin1, Chen Lei2
Received:
2022-11-22
Accepted:
2023-02-24
Online:
2024-01-18
Published:
2023-06-29
Contact:
Xu Bin, Master, Chief physician, Doctoral supervisor, Department of Orthopedics, the First Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
About author:
Liu Baofang, Master candidate, Department of Orthopedics, the First Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
Supported by:
CLC Number:
Liu Baofang, Xu Bin, Chen Lei. Pueraria decoction in the treatment of osteoarthritis: network pharmacology analysis and animal model validation[J]. Chinese Journal of Tissue Engineering Research, 2024, 28(2): 193-199.
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2.3 蛋白互作网络和核心基因的鉴定 通过将靶点基因上传至STRING数据库,可获得靶点基因对应的蛋白互作网络,并将此网络导入Cytoscape软件可视化,根据Cytoscape插件CytoNCA分别计算网络节点的拓扑参数:中间度中心性、贴近中心性、学位中心性、特征向量中心性、基于局部平均连通性的方法、网络中心性,先后根据各个参数数值的中位数运算筛选核心基因2次,运算值域分别为大于6个运算值参数的中位数。最终获得14个核心基因,分别为MAPK1、MAPK14、AKT1、STAT3、FOS、JUN、CDKN1A、ESR1、MAPK3、CCND1、TP53、MYC、RELA、HIF1A,见图3。"
2.5 动物实验验证 在多项研究中已经充分证明槲皮素有治疗骨关节炎的效果,此次实验选取了对差异表达核心基因作用较多的化合物木犀草素作为实验研究对象。通过动物实验验证木犀草素治疗骨关节炎的作用,番红固绿染色显示,对照组软骨表面完整光滑,软骨胶原和软骨结构完整;骨关节炎组软骨表面粗糙,结构破坏严重,软骨胶原丢失较多,软骨基质染色减少;与骨关节炎组比较,治疗组软骨表面相对平整,结构破坏相对减轻,软骨胶原丢失较少,软骨基质染色相对较好,见图5。通过骨关节炎小鼠模型免疫组化实验评价木犀草素在骨关节炎中的抗炎作用,结果显示:与骨关节炎组相比,治疗组的基质金属蛋白酶1和环氧合酶2表达明显减少,胶原蛋白Ⅱ明显增加。总的来说,这些实验表明木犀草素在动物体内具有保护作用,见图6。"
2.6 靶基因的功能分析 此次实验根据R语言“ClusterProfiler包”分析靶基因在GO功能上的主要富集,生物过程包括对氧化应激的反应、金属离子的响应、细胞对化学压力的反应、对脂多糖的反应、对活性氧的反应、细胞对氧化应激的反应;细胞成分包括膜筏、膜微域、转录调节复合体、胞质小泡腔等;分子功能包括DNA结合转录因子结合、RNA聚合酶Ⅱ特异性DNA结合转录因子结合、转录因子的调节、氨基酸的代谢等功能上,见图7A。KEGG功能富集主要有:糖尿病并发症中的AGE-RAGE信号通路、白细胞介素17信号通路、肿瘤坏死因子α信号通路、PI3K/Akt信号通路、Toll样受体信号通路、HIF-1信号通路等,见图7B,其中葛根汤治疗骨关节炎的36个靶基因主要富集在PI3K/Akt信号通路上,6个差异核心基因中有3个富集在此通路上,见图8。"
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