Mechanism of Chaipo Decoction in Alleviating Pyroptosis in Asthmatic Rats via Regulation of NLRP3/Caspase-1/GSDMD Pathway
10.13422/j.cnki.syfjx.20250637
- VernacularTitle:柴朴汤通过调控NLRP3/Caspase-1/GSDMD通路改善哮喘大鼠细胞焦亡的作用机制
- Author:
Guoran PENG
1
;
Beibei CHENG
2
;
Rongzhen DING
2
;
Aiguo DAI
2
Author Information
1. College of Integrated Chinese and Western Medicine，Hunan University of Chinese Medicine， Changsha 410208，China
2. Hunan Provincial Key Laboratory of Vascular Biology and Translational Medicine，Changsha 410208，China
- Publication Type:Journal Article
- Keywords:
bronchial asthma;
Chaipo decoction;
pyroptosis;
nucleotide-binding oligomerization domain-like receptor pyrin domain-containing 3/cysteinyl aspartate-specific protease-1/gasdermin D （NLRP3/Caspase-1/GSDMD） pathway;
traditional Chinese medicine
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(22):135-144
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the therapeutic effects of Chaipo decoction on bronchial asthma in rats and its regulatory effects on the nucleotide-binding oligomerization domain-like receptor pyrin domain-containing protein 3 （NLRP3）/cysteinyl aspartate-specific protease-1 （Caspase-1）/Gasdermin D （GSDMD） pathway， aiming to elucidate its mechanism in ameliorating pyroptosis. MethodsSixty male Sprague-Dawley （SD） rats were randomly divided into six groups （n=10 per group）： normal control， asthma model， Chaipo decoction low-dose （5.0 g·kg-1）， medium-dose （10.0 g·kg-1）， high-dose （20.0 g·kg-1）， and dexamethasone （1.0 mg·kg-1）. The asthma model was established in all groups except the normal control group via ovalbumin （OVA） sensitization and challenge. Rats in the Chaipo decoction groups received intragastric administration of Chaipo decoction at the corresponding doses， while the dexamethasone group was treated with dexamethasone. The normal and model groups were administered equivalent volumes of saline. After 14 days of intervention， asthma symptom scores were assessed. Dynamic lung compliance （Cdyn）， lung resistance （RL）， and functional residual capacity （FRC） were measured using a small animal pulmonary function testing system. Lung tissue pathology was evaluated by hematoxylin-eosin （HE）， Masson's trichrome， and periodic acid-Schiff （PAS） staining. Levels of interleukin （IL）-6， IL-1β， and IL-18 in bronchoalveolar lavage fluid （BALF） were determined by enzyme-linked immunosorbent assay （ELISA）. Expression of NLRP3 and apoptosis-associated speck-like protein （ASC） in lung tissues was assessed by immunohistochemistry （IHC）. Protein levels of NLRP3， Caspase-1， GSDMD， and other pyroptosis-related proteins were measured by Western blot. ResultsCompared with the normal group， the model group exhibited significantly increased asthma symptom scores， inflammatory scores， collagen deposition， PAS scores， RL， FRC， levels of IL-6， IL-1β， and IL-18 in BALF， and expression levels of NLRP3， ASC， and other pyroptosis-related proteins in lung tissue （P0.01）， while Cdyn was significantly decreased （P0.01）. Compared with the model group， all doses of Chaipo decoction markedly improved asthma symptoms， with significantly reduced symptom scores （P0.05， P0.01）. Pulmonary function analysis showed that medium and high doses of Chaipo decoction significantly increased Cdyn （P0.05， P0.01） and decreased RL and FRC （P0.05， P0.01）. Histopathological evaluation indicated that high-dose Chaipo decoction significantly reduced inflammatory scores， collagen deposition， and goblet cell hyperplasia in lung tissue （P0.05， P0.01）. ELISA results showed that all doses of Chaipo decoction significantly decreased IL-6， IL-1β， and IL-18 levels in BALF （P0.05， P0.01）. IHC and Western blot analyses demonstrated that medium and high doses of Chaipo decoction markedly downregulated NLRP3， ASC， and other pyroptosis-related proteins in lung tissue （P0.05， P0.01）. ConclusionChaipo decoction effectively improves pulmonary function and pathological damage in asthmatic rats， potentially by inhibiting the NLRP3/Caspase-1/GSDMD pathway and reducing pyroptosis.
