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| Exploring the mechanism of intestinal barrier dysfunction in septic rats treated with Zengye Tongfu Zhuyu Formula based on cGAS-STING pathway |
| Hits 32 Download times 3 Received:December 26, 2024 |
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| DOI
10.11656/j.issn.1672-1519.2025.04.15 |
| Key Words
sepsis;Zengye Tongfu Zhuyu Formula;cGAS-STING signaling pathway;apoptosis;necroptosis |
| Author Name | Affiliation | E-mail | | GAO Weiwei | Emergency Department, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China | | | GAO Wanpeng | Emergency Department, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China | 408812367@qq.com | | GUAN Peng | Emergency Department, the Second Affiliated Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300250, China | |
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| Abstract
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| [Objective] To explore the effect mechanism of the Zengye Tongfu Zhuyu Formula based on the cGAS-STING signaling pathway in treating intestinal barrier dysfunction in rats with sepsis. [Methods] A rat model of sepsis was established by cecum ligation and perforation（CLP），and 36 healthy SPF-grade male SD rats were randomly divided into the sham-operated group，the model group，and the low- and high-dose groups of Zengye Tongfu Zhuyu Formula，with 9 rats in each group. The intestinal tissues were retrieved after 3 consecutive days of drug administration，and pathological sections were prepared to determine the degree of intestinal damage by Chiu’s score，and the ultrastructure of intestinal cells was observed under an electron microscope. The expression of intestinal cyclic guanosine adenylate synthase（cGAS），stimulator of interferon genes（STING），TANK-binding kinase 1（TBK1），phosphorylated interferon regulatory factor 3（pIRF3），and phosphorylated mixed-spectrum kinase structural domain-like protein（pMLKL） was detected by protein immunoblotting（Western blot）. The apoptosis rate of intestinal cells was detected by the in situ nick end labeling（TUNEL） method. [Results] Compared with the sham-operated group，the relative expression of Chiu’s score，cGAS，STING，TBK1，pIRF3，and pMLKL and the apoptosis rate of intestinal cells were elevated in the model group，and the differences were statistically significant（P<0.01）. Electron microscopy revealed that microvilli in the model group were severely damaged，cell gaps were widened，and intercellular junctions were damaged；compared with the model group，Chiu’s score，relative expression of TBK1 and pIRF3，and apoptosis rate of intestinal cells were reduced in the Zengye Tongfu Zhuyu Formula low-dose group，and the differences were statistically significant（P<0.05 or P<0.01）；in the Zengye Tongfu Zhuyu Formula high-dose group，Chiu’s score，cGAS，STING，TBK1，pIRF3 and pMLKL relative expression and intestinal cell apoptosis rate were all reduced，and the difference was statistically significant（P<0.01）；electron microscopic observation of intestinal structural damage in the Zengye Tongfu Zhuyu Formula low and high dose groups were improved to different degrees. [Conclusion] Zengye Tongfu Zhuyu Formula can inhibit the activation of a cGAS-STING signaling pathway in sepsis，and inhibit apoptosis and necrotic apoptosis by inhibiting the synthesis and phosphorylation of the key proteins and regulatory factors of the downstream pathway，and ultimately maintain the integrity of the intestinal mucosal barrier，and treat the intestinal barrier dysfunction in sepsis. |
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