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Zhongguo shi yan xue ye xue za zhi · 2026

[Integrative Multi-omics Analysis of the Tnf-Pnpla2-Rictor-Nr1d1 Network Underlying the Hemostatic Action of Bletilla Striata].

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Yang Tao, Xiong Yan, Yang Ling, Wang Xing-Gang, Huang Yong, Fu Zhi-Li

Аннотация

OBJECTIVE: By integrating transcriptomics and network pharmacology, we systematically investigated the potential hemostatic mechanism of Bletilla striata (BS).

METHODS: Thirty SPF-grade Kunming mice were randomly divided into three groups (n =10 per group): Control group, Model group, and BS group. The BS group was orally administered Bletilla striata extract (2.48 g/kg) for 7 consecutive days, while the Control and Model groups received an equal volume of 0.5% sodium carboxymethyl cellulose (CMC-Na) solution. On day 7, the Model and BS groups were injected via the tail vein with heparin sodium (0.8 U per mouse) to inducesystemic bleeding. The bleeding time (BT) was measured by tail tip amputation, and coagulation parameters including prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), and plasma fibrinogen (FIB) were measured using a semi-automaticcoagulation analyzer. Liver tissues were collected for total RNA extraction and transcriptome sequencing to identify differentially expressed genes (DEGs) related to coagulation pathways. Network pharmacology was used to construct aprotein-protein interaction (PPI) network, screen hub genes, and perform molecular docking to evaluate the binding affinity between the active component militarineand key target proteins.

RESULTS: Compared with the Model group, preventive treatment with BS significantly shortened BT and CT (P <0.01), and reversed coagulation parameters: APTT, PT, and TT were significantly reduced (P <0.01), while FIB levels were significantly elevated P <0.001). Transcriptome analysis showed that the hepatic gene expression profile in the BS group was closer to that of the Control group. Network pharmacologyidentified Tnf, Rictor, Nrld1 , and Pnpla2 askey hub genes involved in the hemostaticprocess, all of which exhibited favorable binding affinity with militarine. Compared to the control group, the Model group showed a significant decrease in hepatic Tnf expression but significant increases in Rictor, Nr1d1 , and Pnpla2. After preventive intervention with Bletilla striata , the hepatic Tnf expression in the mice was significantly increased compared to the Model group, while Rictor, Nr1d1 , and Pnpla2 significantly decreased. These findings were further validated by RT-PCR and molecular docking analyses.

CONCLUSION: This study reveals that the hemostatic effect of BS is potentially mediated through multi-target synergistic regulation of coagulation factor transcription, coupled with modulations in lipid metabolism and circadian rhythms. It provides a theoretical basis for developing novel hemostatic agents.

Предметные рубрики MeSH

ИП Урсолов Владлен Сергеевич

ИНН 500118482352 · ОГРНИП 314500117700049

Реквизиты и контакты