土贝母来源外泌体对脓毒症诱导急性肺损伤的保护作用

doi:10.11958/20260566

天津医药 ›› 2026, Vol. 54 ›› Issue (6): 591-597.doi: 10.11958/20260566

土贝母来源外泌体对脓毒症诱导急性肺损伤的保护作用

崔志刚¹(), 英策², 张岑³, 李棣华⁴, 卓玉珍⁴, 杨磊⁴^,⁵^,^△()

¹ 天津市南开医院急诊科（邮编300100）
² 天津医科大学研究生院
³ 天津市南开医院重症医学科
⁴ 中西医结合急腹症研究所
⁵ 天津市急腹症器官损伤与中西医修复重点实验室

收稿日期:2026-03-02 修回日期:2026-03-09 出版日期:2026-06-15 发布日期:2026-06-15
通讯作者: ^△E-mail：nkyanglei@126.com
作者简介:崔志刚（1974），男，副主任医师，主要从事中西医结合急救医学方面研究。E-mail：13820312421@163.com
基金资助:
天津市卫健委中西医结合课题(2025105)

The protective effect of exosomes derived from bolbostemma paniculatum on sepsis-induced acute lung injury

CUI Zhigang¹(), YING Ce², ZHANG Cen³, LI Dihua⁴, ZHUO Yuzhen⁴, YANG Lei⁴^,⁵^,^△()

¹ Department of Emergency, Nankai Hospital, Tianjin 300100, China
² Graduate School of Tianjin Medical University
³ Department of Critical Care Medicine
⁴ Institute of Integrated Traditional Chinese and Western Medicine for Acute Abdominal Diseases,, Nankai Hospital, Tianjin
⁵ Tianjin Key Laboratory of Acute Abdomen Disease Associated Organ Injury and ITCWM Repair

Received:2026-03-02 Revised:2026-03-09 Published:2026-06-15 Online:2026-06-15
Contact: ^△E-mail：nkyanglei@126.com

崔志刚, 英策, 张岑, 李棣华, 卓玉珍, 杨磊. 土贝母来源外泌体对脓毒症诱导急性肺损伤的保护作用[J]. 天津医药, 2026, 54(6): 591-597.

CUI Zhigang, YING Ce, ZHANG Cen, LI Dihua, ZHUO Yuzhen, YANG Lei. The protective effect of exosomes derived from bolbostemma paniculatum on sepsis-induced acute lung injury[J]. Tianjin Medical Journal, 2026, 54(6): 591-597.

摘要/Abstract

摘要：

目的探究土贝母来源外泌体（BDNPs）对脓毒症诱导急性肺损伤（ALI）小鼠的保护作用及相关机制。方法采用超高速离心法提取BDNPs，然后分别利用透射电子显微镜和纳米颗粒跟踪分析技术检测BDNPs的表征。建立盲肠结扎穿孔（CLP）诱导的ALI小鼠模型，将30只小鼠随机分为假手术组（Sham组）、模型组（CLP组）和BDNP干预组（BDNPs组），每组10只。造模24 h后取材，HE染色法检测各组小鼠肺组织病理变化；采用qPCR法检测各组肺组织中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1β和IL-18 mRNA表达变化；采用Western blot法检测各组小鼠肺组织中焦亡相关蛋白Nod样受体蛋白3（NLRP3）、消皮素D（GSDMD）和胱天蛋白酶-1（Caspase-1）的表达变化；采用转录组学高通量测序检测各组肺组织中信号通路的变化；采用16S rDNA高通量测序检测肠道菌群的变化。结果超高速离心法成功制备BDNPs。与CLP组相比，BDNPs治疗后可以显著改善肺组织病理损伤和降低肺组织中TNF-α、IL-1β和IL-18 mRNA及NLRP3、GSDMD和Caspase-1蛋白的表达（P<0.05）；KEGG分析表明，与Sham组相比，CLP组IL-17信号通路和TNF-α信号通路等多种炎症信号通路富集，与CLP组相比，BDNPs治疗可以显著降低相关信号通路；BDNPs治疗可以显著改善肠道菌群组成，降低不动杆菌属和志贺氏菌属的相对丰度，并显著增加梭菌属的相对丰度（P<0.05）。结论 BDNPs对CLP诱导的ALI具有明显的保护作用，其作用机制可能与改善肠道菌群、抑制细胞焦亡和降低炎症反应有关。

关键词: 土贝母, 外泌体, 脓毒症, 急性肺损伤, 细胞焦亡

Abstract:

Objective To investigate the protective effect and the related mechanisms of bolbostemma paniculatum-derived nanoparticles (BDNPs) on acute lung injury (ALI) induced by sepsis in mice. Methods BDNPs were extracted by ultracentrifugation, and their characteristics were detected by transmission electron microscopy and nanoparticle tracking analysis. A mouse model of ALI induced by cecal ligation and puncture (CLP) was established. Thirty mice were randomly divided into the sham operation group (Sham group), the model group (CLP group) and the BDNPs treatment group (BDNPs group), with 10 mice in each group. After 24 hours of modeling, lung tissue samples were collected for HE staining to detect pathological changes. q-PCR was used to detect the expression changes of inflammatory factors (TNF-α, IL-1β and IL-18 mRNA) in lung tissue. Transcriptome high-throughput sequencing was used to detect changes in signaling pathways in lung tissue. Western blot assay was used to detect the expression changes of pyroptosis-related proteins (NLRP3, GSDMD and Caspase-1) in lung tissue. 16S rDNA high-throughput sequencing was used to detect changes of intestinal flora. Results BDNP were successfully prepared by ultracentrifugation. Compared with the CLP group, BDNPs treatment could significantly improve the pathological damage of lung tissue and reduce the expression of TNF-α, IL-1β and IL-18 mRNA in lung tissue as well as the expression of NLRP3, GSDMD and Caspase-1 proteins in lung tissue (P<0.05). Compared with the Sham group, KEGG analysis indicated that the IL-17 signaling pathway and TNF-α signaling pathway and other inflammatory signaling pathway were enriched in the CLP group. Compared with the CLP group, BDNPs treatment could significantly reduce the related signaling pathways (P<0.05). BDNPs treatment could significantly improve the composition of intestinal flora, reduce the relative abundance of Acinetobacter and Shigella species, and significantly increase the relative abundance of Clostridium species (P<0.05). Conclusion BDNPs have a significant protective effect on CLP-induced ALI, and the mechanism may be related to improving the intestinal flora, inhibiting pyroptosis and reducing inflammatory responses.

Key words: bolbostemmatis rhizoma, exosomes, sepsis, acute lung injury, pyroptosis

中图分类号:

R631

图/表 8

表1 qPCR引物序列

Tab.1 Primers sequence for qPCR

基因名称	引物序列（5′→3′）	产物大小/bp
GAPDH	上游：AGGTCGGTGTGAACGGATTTG 下游：GGGGTCGTTGATGGCAACA	202
TNF-α	上游：ATCTCTTCCCCACCCCGAAT 下游：GCGCCAAGCATTCAATGAGC	155
IL-1β	上游：GAAATGCCACCTTTTGACAGTG 下游：TGGATGCTCTCATCAGGACAG	116
IL-18	上游：GTGAACCCCAGACCAGACTG 下游：CCTGGAACACGTTTCTGAAAGA	202

图1 BDNPs的表征 A：BDNPs透射电子显微镜图；B：BDNPs粒径分析。

Fig.1 Characterization of BDNPs

图2 各组小鼠肺组织的HE染色（×200）

Fig.2 HE staining of lung tissue from each group of mice (×200)

表2 各组小鼠肺组织中TNF-α、IL-1β和IL-18 mRNA表达水平比较

Tab.2 Comparison of mRNA expression levels of TNF-α, IL-1β and IL-18 in lung tissue between the three groups of mice

组别	TNF-α	IL-1β	IL-18
Sham组	1.00±0.03	1.03±0.25	1.02±0.20
CLP组	2.48±0.12^a	4.12±0.19^a	2.95±0.68^a
BDNPs组	1.46±0.05^b	1.91±0.30^b	1.49±0.19^b
F	169.000^＊＊	76.470^＊＊	11.210^＊＊

图3 各组小鼠肺组织中NLRP3、GSDMD和Caspase-1蛋白的表达情况

Fig. 3 The expression levels of NLRP3, GSDMD and Caspase-1 proteins in the lung tissue of each group of mice

表3 各组小鼠肺组织中的NLRP3、GSDMD和Caspase-1的蛋白表达比较（n=5， $\stackrel{-}{x}\pm s$）

Tab.3 Comparison of protein expression of NLRP3, GSDMD and Caspase-1 in lung tissue between the three groups of mice

组别	NLRP3	GSDMD	Caspase-1
Sham组	0.36±0.06	0.43±0.01	0.29±0.01
CLP组	0.47±0.03^a	0.59±0.26^a	0.76±0.34^a
BDNPs组	0.34±0.04^b	0.45±0.07^b	0.31±0.19^b
F	6.078^＊	40.240^＊＊	100.300^＊＊

图4 转录组学测序检测各组肺组织中相关信号通路的变化 A：Sham组与CLP组间差异基因的韦恩图；B：CLP组与BDNPs组间差异基因的韦恩图；C：3组共同差异基因聚类分析热图；D：与Sham组相比，CLP组上调基因的KEGG图；E：与CLP组相比，BDNPs组下调基因的KEGG图。

Fig.4 Changes of related signaling pathways in lung tissue of each group detected by transcriptomics sequencing

图5 各组小鼠肠道菌群结构变化 A：Sham组、CLP组和BDNPs组间差异菌群的韦恩图；B：Sham组、CLP组和BDNPs组间PCoA图；C：Sham组与CLP组间属水平上微生物的物种组成差异图；D：CLP组与BDNPs组间属水平上微生物的物种组成差异图。

Fig.5 Changes in intestinal microbiota structure of each group of mice

参考文献 23

[1]	SUN B, LEI M, ZHANG J, et al. Acute lung injury caused by sepsis:how does it happen?[J]. Front Med(Lausanne), 2023, 10:1289194. doi:10.3389/fmed.2023.1289194.
[2]	ZHANG L, LI H, LI D, et al. Unraveling the synergy of inflammation and apoptosis in sepsis-induced acute lung injury:Insights and therapeutic perspectives (Review)[J]. Mol Med Rep, 2026, 33(1):31. doi:10.3892/mmr.2025.13741.
[3]	SHEN Y, HE Y, PAN Y, et al. Role and mechanisms of autophagy,ferroptosis,and pyroptosis in sepsis-induced acute lung injury[J]. Front Pharmacol, 2024, 15:1415145. doi:10.3389/fphar.2024.1415145.
[4]	JIANG Y, GAO S, CHEN Z, et al. Pyroptosis in septic lung injury:Interactions with other types of cell death[J]. Biomed Pharmacother, 2023, 169:115914. doi:10.1016/j.biopha.2023.115914.
[5]	QIAO X, YIN J, ZHENG Z, et al. Endothelial cell dynamics in sepsis-induced acute lung injury and acute respiratory distress syndrome:pathogenesis and therapeutic implications[J]. Cell Commun Signal, 2024, 22(1):241. doi:10.1186/s12964-024-01620-y.
[6]	LI Q, SONG X C, LI K, et al. Gut-lung immunometabolic crosstalk in sepsis:from microbiota to respiratory failure[J]. Front Med(Lausanne), 2025, 12:1685044. doi:10.3389/fmed.2025.1685044.
[7]	WANG Q, YU Z H, NIE L, et al. Assessing the impact of gut microbiota and metabolic products on acute lung injury following intestinal ischemia-reperfusion injury:harmful or helpful?[J]. Front Cell Infect Microbiol, 2024, 14:1491639. doi:10.3389/fcimb.2024.1491639.
[8]	YE L, GAO Y, MOK S W F, et al. Modulation of alveolar macrophage and mitochondrial fitness by medicinal plant-derived nanovesicles to mitigate acute lung injury and viral pneumonia[J]. J Nanobiotechnology, 2024, 22(1):190. doi:10.1186/s12951-024-02473-w.
[9]	李菡, 武康雄, 史阔豪, 等. 土贝母化学成分、药理作用及临床应用研究进展[J]. 中国中药杂志, 2021, 46(17):4314-4322.
	LI H, WU K X, SHI K H, et al. Research progress on chemical constituents,pharmacological activities and clinical application of Bolbostemma paniculatum[J]. China Journal of Chinese Materia Medica, 2021, 46(17):4314-4322. doi:10.19540/j.cnki.cjcmm.20210325.601.
[10]	FU J, LIU Z, FENG Z, et al. Platycodon grandiflorum exosome-like nanoparticles:the material basis of fresh platycodon grandiflorum optimality and its mechanism in regulating acute lung injury[J]. J Nanobiotechnology, 2025, 23(1):270. doi:10.1186/s12951-025-03331-z.
[11]	CHENG S, LI Y, SUN X, et al. The impact of glucose metabolism on inflammatory processes in sepsis-induced acute lung injury[J]. Front Immunol, 2024, 15:1508985. doi:10.3389/fimmu.2024.1508985.
[12]	HUANG Y, LI G, LI D, et al. Ethyl caffeate alleviates inflammatory response and promotes recovery in septic-acute lung injury via the TNF-α/NF-κB/MMP9 Axis[J]. Phytomedicine, 2025, 141:156700. doi:10.1016/j.phymed.2025.156700.
[13]	WANG J, LI L L, ZHAO Z A, et al. NLRP3 inflammasome-mediated pyroptosis in acute lung injury:Roles of main lung cell types and therapeutic perspectives[J]. Int Immunopharmacol, 2025, 154:114560. doi:10.1016/j.intimp.2025.114560.
[14]	FENG Y, LI M, YANGZHONG X, et al. Pyroptosis in inflammation-related respiratory disease[J]. J Physiol Biochem, 2022, 78(4):721-737. doi:10.1007/s13105-022-00909-1.
[15]	DING P, YANG R, LI C, et al. Fibroblast growth factor 21 attenuates ventilator-induced lung injury by inhibiting the NLRP3/caspase-1/GSDMD pyroptotic pathway[J]. Crit Care, 2023, 27(1):196. doi:10.1186/s13054-023-04488-5.
[16]	CHEN M, HU C, YANG L, et al. Saikosaponin-D induces the pyroptosis of lung cancer by increasing ROS and activating the NF-κB/NLRP3/caspase-1/GSDMD pathway[J]. J Biochem Mol Toxicol, 2023, 37(8):e23444. doi:10.1002/jbt.23444.
[17]	刘馥溧, 巴元明. NF-κB信号通路在急性肺损伤中的作用及中药干预研究进展[J]. 中国药房, 2025, 36(10):1277-1282.
	LIU F L, BA Y M. Research progress on the role of NF-κB signaling pathway in acute lung injury and TCM intervention[J]. China Pharmacy, 2025, 36(10):1277-1282. doi:10.6039/j.issn.1001-0408.2025.10.22.
[18]	HUANG L, LI Y, CHENG Z, et al. PCSK9 promotes endothelial dysfunction during sepsis via the TLR4/MyD88/NF-κB and NLRP3 pathways[J]. Inflammation, 2023, 46(1):115-128. doi:10.1007/s10753-022-01715-z.
[19]	ZHU D, ZHANG J, HUANG X, et al. Integrated network pharmacology and experimental validation to elucidate the mechanism of celastrol in mitigating sepsis-induced acute lung injury in mice[J]. Phytomedicine, 2025, 141:156678. doi:10.1016/j.phymed.2025.156678.
[20]	PEI H, CHEN J, QU J, et al. S100A9 exacerbates sepsis-induced acute lung injury via the IL17-NFκB-caspase-3 signaling pathway[J]. Biochem Biophys Res Commun, 2024, 710:149832. doi:10.1016/j.bbrc.2024.149832.
[21]	CHEN C, LIN J, WANG X, et al. Novel insights into immune mechanisms in acute lung injury:Focusing on gut microbiota and its metabolites[J]. Microbiol Res, 2025, 300:128279. doi:10.1016/j.micres.2025.128279.
[22]	YI S, ZHUANG X, LUO L, et al. Gut microbiota and metabolites in acute lung injury:mechanisms and therapeutic perspectives[J]. Respir Res, 2026, 27(1):82. doi:10.1186/s12931-026-03525-5.
[23]	YANG L, HE S, WEI A, et al. Gut microbiota-derived proline-leucine dipeptide aggravated sepsis-induced acute lung injury via activating Nod2/NF-κB signaling pathway[J]. Mol Immunol, 2025, 184:199-212. doi:10.1016/j.molimm.2025.05.024.

土贝母来源外泌体对脓毒症诱导急性肺损伤的保护作用

The protective effect of exosomes derived from bolbostemma paniculatum on sepsis-induced acute lung injury

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