1.Mechanism of Chaipo Decoction in Alleviating Pyroptosis in Asthmatic Rats via Regulation of NLRP3/Caspase-1/GSDMD Pathway
Guoran PENG ; Beibei CHENG ; Rongzhen DING ; Aiguo DAI
Chinese Journal of Experimental Traditional Medical Formulae 2025;31(22):135-144
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.
2.The effect of NLRP3 on airway epithelial-mesenchymal transition by regulating Th17/Treg imbalance in asthmatic mice
Beibei CHENG ; Guoran PENG ; Lingling ZHOU ; Feiying WANG ; Silin XIE ; Jian YI ; Aiguo DAI
Immunological Journal 2024;40(5):440-445
This study was designed to explore the correlation between alterations in NLRP3 levels and Th17/Treg imbalance in asthmatic mice undergoing epithelial-mesenchymal transition(EMT).A murine model of asthma was established by intraperitoneal injection combined with nebulization of ovalbumin(OVA).Mice were randomly grouped into asthma model group and normal control group.The airway reactivity was detected with non-invasive lung function instrument.Hematoxylin and Eosin(HE)and Masson's trichrome staining were applied to evaluate the histopathological injury of lung tissue and the extent of lung fibrosis;RT-qPCR was applied to detect EMT-related biomarkers(Snail,E-Cadherin,N-Cadherin),the specific transcription factors of T cell subsets(RoRγt,Foxp3)and NLRP3 in lung tissue of mice;Western blot was used to detect the protein expression of E-cadherin,N-Cadherin and NLRP3 in lung tissue of mice.The Th17 and Treg cell populations in the spleen were enumerated via flow cytometry.Furthermore,the expression levels of NLRP3,IL-17 and IL-10 in bronchoalveolar lavage fluid(BALF)were analyzed by Giemsa staining.Compared with the control group,the asthma model group showed higher level of airway resistance,coupled with an obviously decrease in pulmonary ventilation compliance.Pathological alterations in lung tissue were evident,characterized by thickening of the airway epithelium,airway stenosis,infiltration of inflammatory cells,higher expression levels of N-Cadherin and NLRP3 proteins(P<0.05),lower expression level of E-Cadherin(P<0.001)and higher levels of marker genes(Snail and N-Cadherin)in lung tissue.Furthermore,model mice demonstrated higher level of NLRP3 in BALF(P<0.05),higher level of Th17 in spleen,and higher levels of retinoic acid orphan receptor(ROR)-γt mRNA(P<0.05)and Th17-related cytokines(IL-17)(P<0.01).Concurrently,model mice also showed an obviously decrease in the prevalence of Treg cells,Forkhead box Foxp3 mRNA(P<0.001),and Treg-related cytokine IL-10(P<0.05).The results of the Pearson correlation analysis indicated that the level of NLRP3 mRNA was positively correlated the ratio of RoR γt mRNA,but negatively correlated with Foxp3 mRNA in the lung tissue of asthmatic mice.Additionally,NLRP3 in BALF demonstrated a positive correlation with IL-17 and a negative correlation with IL-10.In conclusion,These findings suggest that NLRP3 may trigger bronchial EMT by exacerbating the immune imbalance of Th17/Treg cells.
3.Exploration on Targeted Pulmonary Vascular Remodeling for the Treatment of Pulmonary Hypertension Based on Collateral Disease Theory
Xianya CAO ; Junlan TAN ; Runxiu ZHENG ; Jian YI ; Guoran PENG ; Rongzhen DING ; Xia LI ; Feiying WANG ; Aiguo DAI
Chinese Journal of Information on Traditional Chinese Medicine 2024;31(9):18-23
Pulmonary hypertension(PH)is a progressive pulmonary vascular disease that can lead to right heart failure and death.In recent years,the incidence of PH has been increasing year by year and there is a lack of effective treatment.TCM can play an important synergistic role in the treatment of PH.Pulmonary vascular remodeling is a core pathological feature of PH,which is closely related to the physiological structure and pathological changes of the collaterals.Based on the collateral disease theory,this article described the key pathogenesis of PH in TCM and Western medicine,including the lesions of the pulmonary and cardiovascular complexes and pulmonary vascular remodeling,analyzed the physiology of the"collateral-vessel"in PH,sorting out the pathological correlation,and explored TCM targeting pulmonary vascular remodeling in the identification and treatment of PH,so as to provide a new way of thinking for the clinical treatment of PH.
4.Therapeutic Observation of Acupuncture plus Auricular Point Sticking forPrimary Dysmenorrhea
Xia DENG ; Xiao XUE ; Guoran PENG ; Chun CHEN ; Panan WANG ; Xin GUO ; Kaipeng LIANG
Shanghai Journal of Acupuncture and Moxibustion 2015;(10):955-957
ObjectiveTo compare the clinical efficacies of acupuncture, auricular point sticking, and the combination of the two methods in treating primary dysmenorrhea by using randomized controlled method, for selecting the optimal treatment in treating primary dysmenorrhea, and to explore the nursing care method for primarydysmenorrhea from the perspective of Chinese medicine. MethodNinety patients with primary dysmenorrhea were randomized into an acupuncture group of 30 cases (group A), an auricular point sticking group of 30 cases (group B), and a combined group of acupuncture plus auricular point sticking of 30 cases (group C). The patients were given treatment 7 d ahead of the menstrual period, a menstrual cycle as a treatment course, totally for 3 courses. The pain score and clinical efficacies were observed and compared among the three groups for statistical analyses.Result The pain scores were significantly changed in the three groups after intervention (P<0.05), there were significant differences in comparing the pain scores among the three groups after intervention (P<0.05), group A and C were superior to group B (P<0.05), and group C was superior to group A (P<0.05). The total effective rate was 96.7% in group A, versus 93.3% in group B and 100.0%in group C, and the rank-sum test showed thatZ=7.675,P=0.022 (P<0.05).ConclusionThe three treatment methods are all effective in treating primary dysmenorrhea, while combining acupuncture and auricular point sticking can approach the optimal effect.

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