森登-4汤治疗骨性关节炎的靶点筛选及验证  

Screening and validation of targets of Senden-4 decoction in the treatment of osteoarthritis

作　　者：金刚[1,2] 徐艳华 郝俊生[3] 金英 乌云达来 赵巴根那 白红柱[1] 吉白格力玛 额希宝力道 JIN Gang;XU Yanhua;HAO Junsheng;JIN Ying;WU Yundalai;ZHAO Bagenna;BAI Hongzhu;J Bai-gal-ma;SH Bol d(Department of Orthopedics,the Affiliated Hospital of Inner Mongolia University for Nationalities,Tongliao 028007,Inner Mongolia,China;International College of Mongolian Medicine,National Medical University,Ulan Bator 15160,Mongolia;Inner Mongolia Tongliao Market Inspection and Testing Center,Tongliao 028000,Inner Mongolia,China;Old Niute Banner,Chifeng 024500,Inner Mongolia,China;Wengniuti Banner Hospital,Chifeng 024500,Inner Mongolia,China)

机构地区：[1]内蒙古民族大学附属医院,内蒙古通辽028007 [2]蒙古国国立医科大学国际蒙医学院,蒙古国乌兰巴托15160 [3]内蒙古自治区通辽市市场检验检测中心,内蒙古通辽028000 [4]内蒙古自治区赤峰市翁牛特旗中蒙医院,内蒙古赤峰024500 [5]内蒙古自治区赤峰市翁牛特旗旗医院,内蒙古赤峰024500

出　　处：《中国骨质疏松杂志》2022年第1期80-83,119,共5页Chinese Journal of Osteoporosis

基　　金：国家民委-教育部蒙医药研发工程重点实验室开放基金项目子课题(MDK2019071);内蒙古自治区自然科学基金项目(2019LH08035);内蒙古民族大学附属医院青年创新基金项目(2019QNJJ06)。

摘　　要：目的筛选并验证森登-4汤治疗骨性关节炎(osteoarthritis,OA)的作用靶点。方法运用网络药理学方法中TCMSP、PubChem等数据库及Swiss target predictionn平台,获得森登-4汤的化合物信息,运用DISgeNET、PharmGkb、OMIM、NCBI等数据库,获OA疾病相关靶点基因。以Merge工具构建“森登-4汤活性成分-靶点-通路”网络图,筛选靶点蛋白。建立家兔OA模型并给予森登-4汤灌胃治疗,采用蛋白质免疫印迹法(western blot,WB)检测家兔膝关节软骨组织基质金属蛋白酶(matrix metalloproteinase9,MMP9)、基质金属蛋白酶(matrix metalloproteinase13,MMP13)蛋白表达。结果通过本研究筛得森登-4治疗OA的13个靶点蛋白,通过WB法对其中MMP9、MMP13蛋白进行验证分析,结果表明,森登-4汤显著下调MMP9、MMP13蛋白表达,与模型组比较有显著差异(P<0.01)。结论筛选了森登-4汤治疗OA的相关靶点。验证了网络药理学与分子生物学方法的一致性,阐明了森登-4汤通过调节MMP9、MMP13等蛋白达到治疗OA的机理所在。Objective To screen and verify the therapeutic targets of Senden-4 decoction in the treatment of osteoarthritis(OA).Methods Compound information of Senden-4 decoction was obtained by using TCMSP,PubChem database,and SWisStar predictionN platform.Target genes related to OA disease were obtained by using DISgeNET,PharmGkb,OMIM,and NCBI database.Merge was used to construct the network diagram of active component-target-pathway of Senden-4 Decoction.The target proteins were screened.The rabbit OA model was established and treated with Senden-4 decoction.The protein expressions of matrix metalloproteinase 9(MMP 9)and matrix metalloproteinases 13(MMP13)were detected with Western blotting(WB).Results Thirteen target proteins for the treatment of OA with Senden-4 were screened in this study.MMP9 and MMP13 proteins were verified and analyzed with WB method.The result showed that Senden-4 decoction significantly down-regulated the expression of MMP9 and MMP13 proteins,and there were significant differences compared with the model group(P<0.01).Conclusion The targets of treatment of OA with Senden-4 decoction are screened.The consistency between network pharmacology and molecular biology is verified.The mechanism of treating OA by regulating MMP9,MMP13,and other proteins is clarified.

关 键 词：森登-4汤 骨性关节炎 网络药理学 靶点筛选 

分 类 号：R285.5[医药卫生—中药学] R684.3[医药卫生—中医学]