泻白散对LPS诱导幼龄大鼠急性肺损伤的调控作用机制

doi:10.11958/20252076

天津医药 ›› 2026, Vol. 54 ›› Issue (2): 151-157.doi: 10.11958/20252076

泻白散对LPS诱导幼龄大鼠急性肺损伤的调控作用机制

张庆玲¹(), 刘仕琦², 付殷³, 李冀³^,^△()

1 黑龙江中医药大学第一临床医学院中医内科学教研室（邮编150040）
2 山西中医药大学基础医学院方剂教研室
3 黑龙江中医药大学基础医学院方剂教研室

收稿日期:2025-06-01 修回日期:2025-10-11 出版日期:2026-02-15 发布日期:2026-02-12
通讯作者: 李冀 E-mail:zhangqinglingtcm@163.com;1424948004@qq.com
作者简介:张庆玲（1993），女，博士在读，主要从事方剂学理论及配伍规律研究。E-mail：zhangqinglingtcm@163.com
基金资助:
国家中医药管理局李冀名老中医药专家传承工作室项目(2014);国家中医药管理局李冀全国名中医传承工作室项目(2022);黑龙江省中医药科研项目(20230830225018);黑龙江省卫生健康委科技计划(20221313050712)

Regulatory mechanism of xiebai san on LPS-induced acute lung injury in juvenile rats

ZHANG Qingling¹(), LIU Shiqi², FU Yin³, LI Ji³^,^△()

1 Department of Internal Medicine of Traditional Chinese Medicine, the First Clinical College of Heilongjiang University of Chinese Medicine, Harbin 150040, China
2 Department of Chinese Medicinal Formulae, College of Basic Medicine, Shanxi University of Traditional Chinese Medicine
3 Department of Chinese Medicinal Formulae, College of Basic Medicine, Heilongjiang University of Chinese Medicine

Received:2025-06-01 Revised:2025-10-11 Published:2026-02-15 Online:2026-02-12
Contact: LI Ji E-mail:zhangqinglingtcm@163.com;1424948004@qq.com

张庆玲, 刘仕琦, 付殷, 李冀. 泻白散对LPS诱导幼龄大鼠急性肺损伤的调控作用机制[J]. 天津医药, 2026, 54(2): 151-157.

ZHANG Qingling, LIU Shiqi, FU Yin, LI Ji. Regulatory mechanism of xiebai san on LPS-induced acute lung injury in juvenile rats[J]. Tianjin Medical Journal, 2026, 54(2): 151-157.

摘要/Abstract

摘要：

目的探讨泻白散（XBS）及联合阿奇霉素（AZM）对脂多糖（LPS）诱导的幼龄大鼠急性肺损伤（ALI）的保护作用及机制。方法采用分层随机法将30只大鼠按体质量分为空白（Control）组、模型（Model）组、AZM组、XBS组及XBS联合AZM（Combined）组，每组6只。除Control组外，其余各组采用雾化吸入LPS建立幼龄大鼠ALI模型。采用生化试剂盒检测肺组织氧化应激因子[超氧化物歧化酶（SOD）、丙二醛（MDA）和过氧化氢酶（CAT）]水平；酶联免疫吸附试验检测血清炎性因子[白细胞介素（IL）-6、IL-10、IL-13和核因子κB（NF-κB）]水平；基于转录组学分析大鼠肺组织差异基因并进行富集分析；免疫组织化学法测定大鼠肺组织中环氧化酶2（COX-2）、肿瘤坏死因子-α（TNF-α）表达水平。结果与Control组相比，Model组大鼠肺组织中SOD、CAT活力降低，MDA含量升高（P<0.05）；血清中IL-6、IL-10、IL-13、NF-κB水平均升高（P<0.05）。与Model组比较，AZM组、Combined组肺组织SOD和CAT活性均升高（P<0.05），XBS组SOD活性亦升高，MDA含量降低（P<0.05）；AZM组、XBS组和Combined组血清IL-6、IL-10、IL-13水平均降低，XBS组NF-κB水平亦降低（P<0.05）。转录组学分析显示，Control组与Model组间的差异基因显著富集于IL-17信号通路。Combined组干预后，可回调S100a8、S100a9、Mmp8等关键基因的表达，显著抑制IL-17通路的激活。免疫组化结果显示，与Control组相比，Model组大鼠肺组织中COX-2、TNF-α表达水平升高（P<0.05）；与Model组相比，AZM组、XBS组和Combined组COX-2表达水平均降低，Combined组肺组织中TNF-α表达水平降低（P<0.05）。结论 XBS及联合AZM可能通过抑制IL-17信号通路，减轻氧化应激与炎症反应，调控相关基因和蛋白表达，从而改善幼龄大鼠ALI。

关键词: 急性肺损伤, 泻白散, 转录组, 阿奇霉素

Abstract:

Objective To elucidate the regulatory mechanism of xiebai san (XBS) and its combination with azithromycin (AZM) on LPS-induced acute lung injury (ALI) in juvenile rats. Methods Thirty rats were divided into the control group, the model group, the AZM group, the XBS group and the XBS combined with AZM (combined) group according to body weight by stratified random method, with 6 rats in each group. In addition to the control group, the other groups were treated with aerosol inhalation of LPS to establish the ALI model of young rats. Levels of superoxide dismutase (SOD), malondialdehyde (MDA) and catalase (CAT) in lung tissue were detected using biochemical kits. Serum interleukin (IL-6, IL-10 and IL-13) and nuclear factor-κB (NF-κB) were measured by enzyme-linked immunosorbent assay. Transcriptomic analysis was performed to identify differentially expressed genes (DEGs) in lung tissue, followed by enrichment analysis. Immunohistochemistry was used to assess cyclooxygenase-2 (COX-2) and tumor necrosis factor-α (TNF-α) expression in lung tissue. Results Compared with the control group, the activities of SOD and CAT in lung tissue of rats decreased in the model group, and the content of MDA increased (P < 0.05). Serum levels of IL-6, IL-10, IL-13 and NF-κB all increased (P < 0.05). Compared with the model group, SOD and CAT activities in lung tissue significantly increased in the AZM group and the combined group（P<0.05), while SOD activity increased and MDA content decreased in the XBS group. Serum inflammatory factors IL-6, IL-10 and IL-13 levels were significantly reduced in the AZM group, the XBS group and the combined group, with NF-κB levels also decreasing in the XBS group（P<0.05). Transcriptomic analysis revealed that XBS and its combination with AZM alleviated ALI by modulating the IL-17 signaling pathway. Immunohistochemistry indicated significantly reduced COX-2 and TNF-α expression in the AZM group, the XBS group and the combined group compared to those of the model group. Conclusion XBS and its combination with azithromycin may ameliorate ALI in juvenile rats by regulating the IL-17 signaling pathway, oxidative stress, inflammatory responses and lung gene expression.

Key words: acute lung injury, Xie Bai San, transcriptome, azithromycin

中图分类号:

R285

图/表 8

表1 各组大鼠肺组织中氧化应激因子水平比较（n=6，$\bar{x}±s$）

Tab.1 Comparison of the expression level of oxidative stress factors in lung tissue of rats between the five groups

组别	SOD/ （U/mgprot）	MDA/ （μmol/gprot）	CAT/ （U/mgprot）
Control组	47.04±4.73	0.74±0.12	22.93±1.72
Model组	37.96±6.69^a	1.04±0.13^a	18.60±1.43^a
AZM组	45.98±7.69^b	0.84±0.20	21.45±4.23^b
XBS组	47.31±7.77^b	0.45±0.12^abc	15.34±2.22^ac
Combined组	44.35±2.81^b	1.27±0.26^bcd	24.76±2.85^bd
F	3.933^＊	18.370^＊	11.514^＊

表2 各组大鼠血清中炎性因子水平比较（n=6，ng/L，$\bar{x}±s$）

Tab.2 Comparison of the expression level of serum inflammatory factors between the five groups

组别	IL-6	IL-10	IL-13	NF-κB
Control组	91.76±7.81	68.71±13.08	30.81±1.82	527.25±56.14
Model组	107.90±3.95^a	105.38±15.73^a	37.42±1.16^a	649.71±74.51^a
AZM组	93.56±6.80^b	84.13±3.68^b	33.17±2.12^b	584.86±28.43
XBS组	93.13±8.51^b	84.65±10.05^b	33.03±1.69^b	554.06±27.88^b
Combined组	94.59±5.40^b	83.08±12.41^b	32.31±1.34^b	608.04±36.14^ad
F	5.864^＊	7.474^＊	13.100^＊	5.828^＊

图1 差异基因表达火山图 A：Control组与Model组间显著性DEGs；B：AZM组与Model组间显著性DEGs；C：XBS组与Model组间显著性DEGs；D：Combined组与Model组间显著性DEGs；红色：上调基因，蓝色：下调基因，灰色：无显著性差异基因。

Fig.1 Differential gene expression volcano map

图2 共同差异基因韦恩图 A：Control组、Model组与AZM组、Model组交集基因；B：Control组、Model组与XBS组、Model组交集基因；C：Control组、Model组与Combined组、Model组交集基因。

Fig.2 Common differential gene Wayne diagram

图3 显著性较高的共同差异基因聚类分析热图

Fig.3 Heat map of common differential gene cluster analysis with high significance

图4 DEGs的KEGG通路和GO功能富集分析 A：KEGG富集分析；B：GO富集分析结果。

Fig.4 KEGG enrichment analysis of differentially expressed genes and GO enrichment analysis of differentially expressed genes

图5 大鼠肺组织中炎性因子免疫组化分析（IHC，×200）

Fig.5 Immunohistochemical analysis of inflammatory factors in rat lung tissue (IHC，×200)

表3 各组大鼠肺组织中COX-2、TNF-α表达水平比较（n=6，$\bar{x}±s$）

Tab.3 Comparison of expression levels of serum inflammatory factors between the five groups of rats

组别	COX-2/（ng/L）	TNF-α/（ng/L）
Control组	17.38±0.20	16.42±0.11
Model组	27.50±0.58^a	26.34±0.45^a
AZM组	22.25±0.06^ab	18.67±0.05
XBS组	23.72±0.36^abc	23.72±0.36^a
Combined组	19.32±0.23^abcd	17.30±0.03^b
F	397.069^＊	781.689^＊

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泻白散对LPS诱导幼龄大鼠急性肺损伤的调控作用机制

Regulatory mechanism of xiebai san on LPS-induced acute lung injury in juvenile rats

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