中国病理生理杂志2026，Vol.42Issue(5)：974-984,11.DOI:10.3969/j.issn.1000-4718.2026.05.015
土贝母苷甲通过抑制细胞焦亡减轻脓毒症小鼠急性肺损伤
Tubeimoside I alleviates acute lung injury in mice with sepsis by sup-pressing pyroptosis
摘要
Abstract
AIM:This study aims to investigate the protective effects of tubeimoside I(TBMS1)against sep-sis-induced acute lung injury(SI-ALI)in mice,and to evaluate its potential mechanism.METHODS:A total of 108 C57BL/6 mice were randomly divided into 6 groups(18 mice in each group):control,cecal ligation and puncture(CLP),CLP+low-dose(1 mg/kg)TBMS1,CLP+medium-dose(2 mg/kg)TBMS1,CLP+high-dose(4 mg/kg)TBMS1,and CLP+dexamethasone(5 mg/kg).The SI-ALI model was established through CLP after the last drug administration.At 24 h after CLP,bronchoalveolar lavage fluid(BALF),lung tissue and serum samples were collected for subsequent experiments.Hematoxylin-eosin(HE)staining was used to analyze histopathological changes of lung tissues.The lung wet-to-dry weight(W/D)ratio was estimated using wet/dry weighing method.Tumor necrosis factor-α(TNF-α)and interleukin(IL)levels,protein content,immune cell counts in BALF or serum,and myeloperoxidase(MPO)activity in lung tissues were measured using enzyme-linked immunosorbent assay(ELISA)and Wright-Giemsa staining.Western blotting was used to measure the protein expression of zonula occludens-1(ZO-1),occludin,nucleotide-binding oligomerization domain-like receptor 3(NLRP3),apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),caspase-1,gasdermin D(GSDMD),IL-1β and IL-18 in mouse lung tissues.Lipopolysaccharide(LPS)-stimulated mouse type II alveolar epithelial cells(MLE-12)were used to construct an in vitro SI-ALI model.The MLE-12 cells were treated with different concentrations of TBMS1 for 24 h in the presence of LPS.The effect of TBMS1 on the pyroptotic phenotype of MLE-12 cells was evaluated using Hoechst 33342/propidium iodide(PI)staining and lactate dehydrogenase(LDH)re-lease assay.Alveolar epithelial barrier markers,pyroptosis-related proteins,and the secretion of proinflammatory cyto-kines from MLE-12 cells were detected by immunofluorescence staining,Western blot and ELISA.RESULTS:Com-pared with control group,the mice in CLP group showed disrupted lung tissue structure,alveolar wall thickening,and in-flammatory cell infiltration.The lung W/D ratio,MPO activity in lung tissues,protein content,neutrophil and macrophage accumulation,and proinflammatory cytokine levels(TNF-α,IL-1β,IL-6 and IL-18)in BALF or serum were significantly higher in CLP group than those in control group(P<0.01).In addition,the CLP group showed markedly reduced protein expression of ZO-1 and occludin,and increased protein expression of NLRP3,ASC,caspase-1,GSDMD,GSDMD-N,IL-1β,and IL-18 in lung tissues(P<0.01).In vitro experiments revealed that the proportion of PI-positive MLE-12 cells and LDH release were markedly higher in LPS group than those in control group(P<0.01).The cells in LPS group exhibited markedly reduced expression of ZO-1 and occludin(P<0.01)and substantially increased expression of pyroptosis-related proteins and proinflammatory cytokines(P<0.01).Pre-administration of TBMS1 at medium-to-high doses significantly al-leviated pulmonary histological damage and improved survival in mice with sepsis(P<0.05 or P<0.01).Furthermore,TBMS1 treatment resulted in significant reductions in the lung W/D ratio,MPO activity in lung tissues,and total protein concentration and proinflammatory cytokine levels in both BALF and serum(P<0.05 or P<0.01).Medium-to-high doses of TBMS1 markedly decreased sepsis-induced expression of pyroptosis-specific proteins while significantly increasing the protein expression of alveolar epithelial barrier markers in the lung tissues of mice with sepsis(P<0.05 or P<0.01).More-over,TBMS1 treatment at medium-to-high doses decreased the expression of pyroptosis indicators and pyroptosis-related proteins in LPS-stimulated MLE-12 cells(P<0.05 or P<0.01).CONCLUSION:Treatment with TBMS1 alleviates SI-ALI by suppressing the canonical pyroptosis signaling pathway.关键词
土贝母苷甲/脓毒症/急性肺损伤/肺泡上皮细胞/细胞焦亡Key words
tubeimoside I/sepsis/acute lung injury/alveolar epithelial cells/pyroptosis分类
医药卫生引用本文复制引用
邱艺巧,郝晓燕,李家馨,单莉娅,陈立轩,张亮..土贝母苷甲通过抑制细胞焦亡减轻脓毒症小鼠急性肺损伤[J].中国病理生理杂志,2026,42(5):974-984,11.基金项目
新疆生产建设兵团科技计划(No.2025ZD006 （）
No.2025DB048) （）
国家自然科学基金资助项目(No.81600325) （No.81600325）
国家级大学生创新创业训练计划项目(No.202510759018) （No.202510759018）
