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| Asiaticoside alleviates renal injury in chronically hypoxic rats by modulating the NLRP3/Caspase-1/GSDMD signaling pathway |
| Hits 142 Download times 85 Received:March 10, 2026 |
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| DOI
10.11656/j.issn.1673-9043.2026.08.06 |
| Key Words
asiaticoside;hypobaric hypoxia;kidney injury;NLRP3;pyroptosis |
| Author Name | Affiliation | E-mail | | DUAN Zheng | Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | | | YANG Danning | Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | | | CAO Ruiqi | Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | | | NIE Yazhen | Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | | | CHEN Cheng | Graduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | | | LIU Weili | Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | | | CHEN Zhaoli | Academy of Military Medicine, Academy of Military Sciences, Tianjin 300050, China | zhaolichen@126.com |
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| Abstract
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| [Objective] To investigate the protective mechanism of asiaticoside（AS）against renal injury in rats exposed to chronic hypobaric hypoxia. [Methods] A simulated high altitude environment（approximately 6 000 meters，with a partial pressure of oxygen of about 11.0 kPa for 23 h/d）was created using an animal hypobaric hypoxia chamber. Thirty-two Wistar rats were randomly divided into four groups（n=8 each）：a normoxic control group（Normoxia），a hypobaric hypoxia model group（HH），a low-dose asiaticoside intervention group（HH+40AS， 40 mg/kg），and a high dose asiaticoside intervention group（HH + 80AS，80 mg/kg）. After the experiment，the following assessments were performed：24 hour urinary indices，serum creatinine（Scr），and blood urea nitrogen （BUN）levels；renal histopathological changes observed via hematoxylin-eosin（HE）staining，Masson’s trichrome staining，and periodic acid Schiff（PAS）staining；renal cell death detected by TUNEL staining；oxidative stress levels in serum and renal tissue measured using kits for superoxide dismutase（SOD），malondialdehyde（MDA），and lactate dehydrogenase（LDH）；serum and renal tissue levels of inflammatory factors [interleukin 1β（IL 1β）， interleukin-18（IL-18）] measured by enzyme-linked immunosorbent assay（ELISA）；and protein expression levels of NOD-like receptor thermal protein domain-associated protein 3（NLRP3），apoptosis-associated speck-like protein containing a CARD（ASC），Caspase 1，cleaved Caspase 1（p20），gasdermin D（GSDMD），and its N terminal fragment（GSDMD-N）in renal tissue determined by Western blot. [Results] Compared with the Normoxia group， the HH group showed significant renal histopathological damage，increased 24-hour urinary indices，Scr，and BUN， a higher number of TUNEL-positive cells，upregulated levels of MDA，LDH，IL-1β，and IL-18 in both renal tissue and serum，significantly increased protein expression of NLRP3，ASC，cleaved Caspase-1（p20），and GSDMD-N（P< 0.01），and significantly decreased SOD levels in renal tissue and serum（P<0.01）. Asiaticoside intervention， especially in the HH+80AS group，markedly improved renal function indicators，alleviated renal histopathological damage and cell death，reduced inflammatory factor levels，and dose dependently inhibited the activation of the NLRP3 inflammasome and the cleavage of downstream GSDMD. [Conclusion] Asiaticoside can alleviate pyroptosis and oxidative stress in rat renal tissue by inhibiting the activation of the NLRP3/Caspase 1/GSDMD signaling pathway，thereby mitigating renal tissue injury and fibrosis induced by chronic hypobaric hypoxia. |
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