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野马追倍半萜内酯对脂多糖诱导大鼠急性肺损伤的保护作用研究
Study on the protective effect of sesquiterpene lactones of
Eupatorium lindleyanum DC. on lipopolysaccharide-induced acute lung injury in rats- 重庆医科大学学报 2025年50卷第7期 页码：889-897
- 作者机构：
重庆医科大学中医药学院，重庆 400016
- 作者简介：
罗 陈，Email：MorningstarLuo@outlook.com，研究方向：中药药理毒理研究评价。
罗先钦，Email：lxq_0203@163.com。
- 基金信息：重庆市自然科学基金面上资助项目(cstc2021jcyj-msxmX0365);重庆市教委科学技术研究计划重点资助项目(KJZD-K202215101);四川省科学技术厅川渝科技创新合作资助项目(2024YFHZ0083)
DOI：10.13406/j.cnki.cyxb.003853
中图分类号： R285.5收稿：2025-03-16，
修回：2025-04-09，
录用：2025-04-21，
纸质出版：2025-07-28
- 稿件说明：
移动端阅览
罗陈,杨燕,令狐莉,等.野马追倍半萜内酯对脂多糖诱导大鼠急性肺损伤的保护作用研究[J].重庆医科大学学报,2025,50(7):889-897.
Luo Chen,Yang Yan,Linghu Li,et al.Study on the protective effect of sesquiterpene lactones of Eupatorium lindleyanum DC. on lipopolysaccharide-induced acute lung injury in rats[J].Journal of Chongqing Medical University,2025,50(7):889-897.
罗陈,杨燕,令狐莉,等.野马追倍半萜内酯对脂多糖诱导大鼠急性肺损伤的保护作用研究[J].重庆医科大学学报,2025,50(7):889-897. DOI： 10.13406/j.cnki.cyxb.003853.
Luo Chen,Yang Yan,Linghu Li,et al.Study on the protective effect of sesquiterpene lactones of Eupatorium lindleyanum DC. on lipopolysaccharide-induced acute lung injury in rats[J].Journal of Chongqing Medical University,2025,50(7):889-897. DOI： 10.13406/j.cnki.cyxb.003853.
摘要
目的
2
旨在通过代谢组学探讨野马追倍半萜内酯（sesquiterpene lactones of
Eupatorium lindleyanum
DC.，SLEL）对脂多糖（lipopo
lysaccharide，LPS）诱导急性肺损伤（acute lung injury，ALI）模型大鼠的保护作用。
方法
2
将48只SD雄性大鼠随机分为空白对照组（control group，CG）、模型对照组（model group，MG）、SLEL低、中、高剂量组（50、100、200 mg/kg）和阳性对照组（醋酸地塞米松片，5 mg/kg），其中CG组和MG组给予磷酸盐缓冲液（phosphate-buffered saline，PBS），各组灌胃给药体积均为10 mL/kg，每天给药1次，连续7 d。末次给药后1 h，除CG组外，其余各组大鼠均气管滴注5 mg/kg LPS建立ALI大鼠模型。造模24 h后，腹主动脉取血并收集左肺肺泡灌洗液（bronchoalveolar lavage fluid，BALF）。采用瑞氏-吉姆萨染色法计数BALF的总炎性细胞、中性粒细胞、淋巴细胞、嗜酸性粒细胞数；酶联免疫吸附测定法检测血清和BALF中白细胞介素-18（interleukin-18，IL-18）和干扰素-γ（interferon-γ，IFN-γ）的含量；苏木精-伊红染色观察肺组织病理改变；蛋白免疫印迹技术（Western blot）检测肺组织紧密连接蛋白-1（zonula occludens-1，ZO-1）和闭合蛋白（Occludin）的蛋白表达；实时定量逆转录聚合酶链反应（quantitative reverse transcription polymerase chain reaction，qRT-PCR）法检测肺脏IL-18、IFN-γ、ZO-1和Occludin的mRNA表达；超高效液相色谱-电喷雾电离-串联质谱（UPLC-ESI-MS/MS）对大鼠的血清和肺组织进行非靶向代谢组学分析。
结果
2
与MG组相比，SLEL各剂量组均明显降低肺组织的湿干重比、肺系数和BALF的总炎性细胞、中性粒细胞、淋巴细胞、嗜酸性粒细胞的数量；均明显降低血清和BALF中IL-18和IFN-γ的含量以及肺组织中IL-18和IFN-γ的mRNA表达；也能够明显促进ZO-1和Occludin的蛋白和mRNA表达；光镜下可见肺组织水肿程度、肺泡腔内出血和炎症细胞浸润明显减轻，显示对ALI大鼠具有一定的保护作用；非靶向代谢组学研究结果显示SLEL血清和肺组织分别有91和33种代谢产物差异明显，其中血清中主要差异代谢物为鞘氨醇、L-乳酸、烟酸D-核苷酸及甲羟戊酸-5P，肺组织中主要差异代谢物为牛磺胆酸，提示SLEL可能主要影响血清的鞘脂、丙酮酸、烟酸和烟酰胺、色氨酸等代谢通路以及肺组织的牛磺酸和亚牛磺酸等代谢通路而改善ALI。
结论
2
SLEL对LPS诱导ALI大鼠具有明显保护作用，其作用机制可能与抑制炎症因子、改善肺部屏障功能以及调控相关代谢通路相关。
Abstract
Objective
2
To explore the protective effect of sesquiterpene lactones of
Eupatorium lindleyanum
DC.（SLEL） on lipopolysaccharide（LPS）-induced acute lung injury（ALI） in rats using metabolomics.
Methods
2
Forty-eight male SD rats were randomly divided into a blank control group（CG），a model control group（MG），low-，medium-，and high-dose SLEL groups（50，100，and 200 mg/kg），and a positive control group（dexamethasone acetate tablets，5 mg/kg）. CG and MG groups were given phosphate-buffered saline. All groups received intragastric administration at a dose volume of 10 mL/kg once a day for 7 consecutive days. One hour after the last administration，LPS（5 mg/kg） was instilled into the trachea of all groups except the CG group to establish the ALI rat model. Twenty-four hours after model establishment，blood was collected from the abdominal aorta and bronchoalveolar lavage fluid（BALF） was collected from the left lung. The total number of inflammatory cells，neutrophils，lymphocytes，and eosinophils in BALF was counted by Wright-Giemsa staining. The levels of interleukin-18（IL-18） and interferon-γ（IFN-γ） in serum and BALF were measured by enzyme-linked immunosorbent assay. The pathological changes of lung tissue were observed using hematoxylin-eosin staining. The expression levels of tight junction protein-1（ZO-1） and occludin in lung tissue were determined by Western blot. The mRNA expression levels of IL-18，IFN-γ，ZO-1，and occludin in the lung were measured by real-time fluorescence quantitative PCR. Non-targeted metabolomics analysis of serum and lung tissue was performed using ultra-performance liquid chromatography-electrospray ionization-tandem mass spectrometry.
Results
2
Compared with the MG group，all SLEL groups had significantly reduced wet/dry weight ratio of lung tissue，lung coefficient，and total number of inflammatory cells，neutrophils，lymphocytes，and eosinophils in BALF. SLEL significantly decreased the levels of IL-18 and IFN-γ in serum and BALF and the mRNA expression of IL-18 and IFN-γ in lung tissue，and significantly promoted the protein and mRNA expression of ZO-1 and occludin. Under light microscopy，the degree of lung tissue edema，alveolar hemorrhage，and inflammatory cell infiltration were significantly reduced，indicating a certain protective effect on ALI rats. The results of non-targeted metabolomics studies showed that there were 91 and 33 significantly different metabolites in the serum and lung tissue of rats treated with SLEL，respectively. Among them，the main differential metabolites in the serum were sphingosine，L-lactic acid，nicotinic acid，D-nucleotide，and mevalonate-5P，while the main differential metabolites in the lung tissue were taurocholic acid. This suggests that SLEL may mainly affect the metabolic pathways of sphingolipids，pyruvate，nicotinic acid，nicotinamide，and tryptophan in the serum and the metabolic pathways of taurine and hypotaurine in the lung tissue to improve ALI.
Conclusion
2
SLEL has a significant protective effect on rats against LPS-induced ALI，and its mechanism of action may be related to the inhibition of inflammatory factors，improvement of lung barrier function，and regulation of related metabolic pathways.
关键词
Keywords
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