基于网络药理学与实验验证探讨三叶青治疗脓毒症的作用及机制  

Effect of Tetrastigma hemsleyanum on sepsis and mechanism based on network pharmacology and experimental verification

作　　者：郑静茹 季春莲[2] 占靓卉 浦锦宝[2,3] 姚立[1] ZHENG Jing-ru;JI Chun-lian;ZHAN Liang-hui;PU Jin-bao;YAO Li(Cllege of Pharmaceutical Sciences,Zhejiang Chinese Medical University,Hangzhou 310053,China;Tongde Hospital of Zhejiang Province,Hangzhou 310014,China;Zhejiang Academy of Traditional Chinese Medicine,Hangzhou 310014,China)

机构地区：[1]浙江中医药大学药学院,浙江杭州310053 [2]浙江省立同德医院,浙江杭州310014 [3]浙江省中医药研究院,浙江杭州310014

出　　处：《中国中药杂志》2022年第17期4744-4754,共11页China Journal of Chinese Materia Medica

基　　金：浙江省中医药科技计划项目(2021ZA026)。

摘　　要：基于网络药理学和体内实验验证探讨三叶青对脓毒症的治疗作用及机制。利用网络药理学的方法获取三叶青与脓毒症的交集靶点,构建“三叶青-化合物-靶标-脓毒症”网络,使用STRING数据库构建蛋白相互作用网络,并采用DAVID数据库进行Gene Ontology(GO)及Kyoto Encyclopedia of Genes and Genomes(KEGG)富集分析,预测三叶青治疗脓毒症的作用机制。采用动物实验对网络药理学部分预测结果进行验证。网络药理学结果表明,三叶青治疗脓毒症的关键靶点涉及肿瘤坏死因子(tumor necrosis factor, TNF)、白细胞介素-6(interleukin-6,IL-6)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-10(interleukin-10,IL-10)和半胱氨酸蛋白酶-3(cysteinylasparate specific proteinase 3,caspase-3),并且可能与Toll样受体4(Toll-like receptor, TLR4)/髓样分化因子(myeloid differentiation factor 88,MyD88)/核因子κB(nuclear factor kappaB,NF-κB)信号通路有关。动物实验结果显示,三叶青能够显著降低C反应蛋白(C-reactive protein, CRP)、降钙素原(procalcitonin, PCT)、乳酸脱氢酶(lactate dehydrogenase, LDH)、IL-6、TNF-α和IL-1β含量,显著升高IL-10含量;同时能够显著下调B淋巴细胞瘤-2基因相关X蛋白(Bcl2-associated X,Bax)/B淋巴细胞瘤-2基因(B-cell lymphoma 2,Bcl2)、cleaved caspase-3、TLR4、MyD88及p-NF-κB p65/NF-κB p65蛋白水平。综上,三叶青通过作用于炎症和细胞凋亡相关的基因TNF-α、IL-6、IL-1β、IL-10、Bax、Bcl2、cleaved caspase-3等,在脓毒症治疗中发挥抗炎作用,其机制可能与抑制TLR4/MyD88/NF-κB信号通路有关,验证了网络药理学预测结果。Based on network pharmacology and in vivo experiment, this study explored the therapeutic effect of Tetrastigma hemsle-yanum(SYQ) on sepsis and the underlying mechanism. The common targets of SYQ and sepsis were screened out by network pharmacology, and the "SYQ-component-target-sepsis" network was constructed. The protein-protein interaction(PPI) network was established by STRING. Gene Ontology(GO) term enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment were performed based on DAVID to predict the anti-sepsis mechanism of SYQ. The prediction results of network pharmacology were verified by animal experiment. The network pharmacology results showed that the key anti-sepsis targets of SYQ were tumor necrosis factor(TNF), interleukin(IL)-6, IL-1β, IL-10, and cysteinyl asparate specific proteinase 3(caspase-3), which were mainly involved in Toll-like receptor 4(TLR4)/myeloid differentiation factor 88(MyD88)/nuclear factor kappaB(NF-κB) signaling pathway. The results of animal experiment showed that SYQ can decrease the content of C-reactive protein(CRP), procalcitonin(PCT), lactate dehydrogenase(LDH), IL-6, TNF-α, and IL-1β, increase the content of IL-10, and down-regulate the protein levels of Bcl-2-associa-ted X(Bax)/B-cell lymphoma 2(Bcl2), cleaved caspase-3, TLR4, MyD88, and p-NF-κB p65/NF-κB p65. In summary, SYQ plays an anti-inflammatory role in the treatment of sepsis by acting on the key genes related to inflammation and apoptosis, such as TNF-α, IL-6, IL-lβ, IL-10, Bax, Bcl2, and cleaved caspase-3. The mechanism is the likelihood that it suppresses the TLR4/MyD88/NF-κB signaling pathway, which verifies relative prediction results of network pharmacology.

关 键 词：三叶青 网络药理学 脓毒症 炎症 

分 类 号：R285[医药卫生—中药学]