1.河南中医药大学药学院,郑州 450046
2.河南中医药大学中医药科学院,郑州 450046
Received:20 August 2025,
Revised:2026-01-15,
Accepted:16 January 2026,
Published:15 February 2026
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陈朝华,谢淑敏,常万顺,等.连翘-金银花药对调控血清外泌体miRNA对急性肺损伤的改善作用及机制研究 [J].中国药房,2026,37(03):305-310.
CHEN Zhaohua,XIE Shumin,CHANG Wanshun,et al.Ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury via regulating serum exosomal miRNA[J].ZHONGGUO YAOFANG,2026,37(03):305-310.
陈朝华,谢淑敏,常万顺,等.连翘-金银花药对调控血清外泌体miRNA对急性肺损伤的改善作用及机制研究 [J].中国药房,2026,37(03):305-310. DOI: 10.6039/j.issn.1001-0408.2026.03.06.
CHEN Zhaohua,XIE Shumin,CHANG Wanshun,et al.Ameliorative effect and mechanism of Forsythia suspensa-Lonicera japonica herb pair on acute lung injury via regulating serum exosomal miRNA[J].ZHONGGUO YAOFANG,2026,37(03):305-310. DOI: 10.6039/j.issn.1001-0408.2026.03.06.
目的
2
基于血清外泌体微RNA(miRNA),研究连翘-金银花药对对急性肺损伤(ALI)的改善作用及机制。
方法
2
将大鼠分为空白组(生理盐水)、模型组(生理盐水)、连翘-金银花药对组(2.55 g/kg),每组10只。除空白组外,其余各组大鼠均通过气管滴注5 mg/mL脂多糖复制ALI模型。造模后,各组大鼠灌胃相应药液/生理盐水,每天1次,连续3 d。末次给药后,观察大鼠肺组织病理学形态;测定肺组织湿干重比和支气管肺泡灌洗液(BALF)中白细胞数量;检测BALF中炎症因子[肿瘤坏死因子α(TNF-α)、白细胞介素1β(IL-1β)、IL-10]水平;提取大鼠血清外泌体,利用高通量测序技术筛选外泌体中差异表达miRNA,并进行京都基因与基因组百科全书(KEGG)富集分析。基于筛选的差异表达miRNA和富集的KEGG通路,通过体外细胞实验进行机制验证。
结果
2
动物实验结果显示,经连翘-金银花药对干预后,ALI大鼠湿干重比以及BALF中白细胞数量和TNF-α、IL-1β水平均显著降低/减少(
P
<0.01),IL-10水平显著升高(
P
<0.01)。高通量测序实验结果显示,连翘-金银花药对可显著上调外泌体中miR-345-3p、miR-194-5p、miR-653-5p等的表达,其中差异表达miRNA的靶基因涉及的KEGG通路包括缺氧诱导因子1(HIF-1)信号通路等。细胞验证实验结果显示,过表达的miR-345-3p可显著升高细胞上清液中IL-10水平(
P
<0.01),显著降低细胞上清液中TNF-α、IL-1β水平以及细胞中蛋白激酶B1、磷脂酰肌醇3-激酶、HIF-1α的mRNA及其蛋白表达水平(
P
<0.01)。
结论
2
连翘-金银花药对可通过上调血清外泌体中miR-345-3p表达,抑制HIF-1信号通路活性,从而减轻炎症反应,进而发挥改善ALI的作用。
OBJECTIVE
2
To study the ameliorative effect and mechanism of
Forsythia suspensa-Lonicera japonica
herb pair on acute lung injury (ALI) based on serum exosomal microRNA (miRNA).
METHODS
2
The rats were randomly divided into a blank group (normal saline), model group (nomal saline), and
F. suspensa-L. japonica
herb pair group (2.55 g/kg), with 10 rats in each group. Except for the blank group, the other groups were used to establish an ALI model by intratracheal dripping of 5 mg/mL lipopolysaccharides. After modeling, each group was given relevant medicine/normal saline intragastrically, once a
day, for 3 consecutive days. After the last medication, the pathological status of lung tissue was observed; lung wet-to-dry weight ratio and leukocyte counts in bronchoalveolar lavage fluid (BALF) were determined. The levels of inflammatory factors [tumor necrosis factor-α(TNF-α), interleukin-1β (IL-1β), IL-10
]
in BALF were determined. Exosomes were isolated from rat serum, and high-throughput sequencing technology was employed to screen differentially expressed miRNA within the exosomes, followed by Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Based on the screened differentially expressed miRNA and the enriched KEGG pathways,
in vitro
cellular experiments were conducted for validation.
RESULTS
2
The animal experimental results demonstrated that after intervention with the
F. suspensa-L. japonica
herb pair, the wet-to-dry weight ratio, the number of leukocytes in BALF, as well as the levels of TNF-α and IL-1β in BALF of ALI rats were all significantly reduced (
P
<0.01), while the level of IL-10 was significantly increased (
P
<0.01). The results of high-throughput sequencing experiments revealed that the
F. suspensa-L. japonica
herb pair could significantly up-regulate the expressions of miR-345-3p, miR-194-5p, miR-653-5p, and others in exosomes. Among them, the KEGG pathways involved in the target genes of differentially expressed miRNA included the hypoxia-inducible factor-1(HIF-1) signaling pathway, among others. The results of cellular validation experiments showed that overexpressed miR-345-3p could significantly elevate the level of IL-10 in the cell supernatant (
P
<0.01), while significantly reducing the levels of TNF-α and IL-1β in the cell supernatant, as well as the mRNA and protein expression levels of protein kinase B1, phosphatidylinositol 3-kinase, and HIF-1α (
P
<0.01).
CONCLUSIONS
2
F. suspensa-L. japonica
herb pair can alleviate inflammatory responses and thereby exert a therapeutic effect in improving ALI by up-regulating the expression of miR-345-3p in serum exosomes and inhibiting the activity of the HIF-1 signaling pathway.
LIANG D J , SUN Y , SHEN Y B , et al . Shikonin exerts anti-inflammatory effects in a murine model of lipopoly- saccharide-induced acute lung injury by inhibiting the nuclear factor-κB signaling pathway [J ] . Int Immunopharmacol , 2013 , 16 ( 4 ): 475 - 480 .
李康 , 吕田田 , 崔荣洽 , 等 . 基于血清代谢组学探讨青翘、老翘对急性肺损伤大鼠的作用机制 [J ] . 中国实验方剂学杂志 , 2024 , 30 ( 18 ): 89 - 97 .
张稚鲲 , 王若尧 , 陈仁寿 . 古今肺系疫病方配伍特点对比研究 [J ] . 中医药信息 , 2018 , 35 ( 4 ): 73 - 76 .
WEN X , CHENG M , SONG Z X , et al . Molecular mechanism of honeysuckle + forsythia in treatment of acute lung injury based on network pharmacology [J ] . Biomed Rep , 2024 , 20 ( 2 ): 32 .
薛丙权 , 朱艳慧 , 余海艳 , 等 . 基于UPLC-Q-TOF-MS/MS和网络药理学研究连翘治疗急性肺损伤的作用机制 [J ] . 中国医院药学杂志 , 2022 , 42 ( 21 ): 2208 - 2215 .
ZHOU Y , LI P F , GOODWIN A J , et al . Exosomes from endothelial progenitor cells improve the outcome of a murine model of sepsis [J ] . Mol Ther , 2018 , 26 ( 5 ): 1375 - 1384 .
YI X M , WEI X X , LV H J , et al . Exosomes derived from microRNA-30b-3p-overexpressing mesenchymal stem cells protect against lipopolysaccharide-induced acute lung injury by inhibiting SAA3 [J ] . Exp Cell Res , 2019 , 383 ( 2 ): 111454 .
ZHANG D , LEE H , WANG X Y , et al . A potential role of microvesicle-containing miR-223/142 in lung inflammation [J ] . Thorax , 2019 , 74 ( 9 ): 865 - 874 .
黄宁 , 胡长平 . 外泌体在肺部疾病中的研究进展 [J ] . 中国药理学通报 , 2023 , 39 ( 11 ): 2006 - 2011 .
LV K Y , LIANG Q . Macrophages in sepsis-induced acute lung injury:exosomal modulation and therapeutic potential [J ] . Front Immunol , 2025 , 15 : 1518008 .
ZHOU W , YIN A L , SHAN J J , et al . Study on the rationa- lity for antiviral activity of Flos Lonicerae Japonicae-Fructus Forsythiae herb chito-oligosaccharide via integral pharmacokinetics [J ] . Molecules , 2017 , 22 ( 4 ): 654 .
秦丽 , 向盈 , 李涵 , 等 . 益气活血方对脂多糖致急性肺损伤大鼠肺气血屏障功能的影响 [J ] . 北京中医药大学学报 , 2024 , 47 ( 12 ): 1702 - 1709 .
黄继汉 , 黄晓晖 , 陈志扬 , 等 . 药理试验中动物间和动物与人体间的等效剂量换算 [J ] . 中国临床药理学与治疗学 , 2004 , 9 ( 9 ): 1069 - 1072 .
余亚辉 , 吕田田 , 薛丙权 , 等 . 外泌体装载连翘酯苷A递药系统的制备及体外评价 [J ] . 中国中药杂志 , 2021 , 46 ( 11 ): 2824 - 2829 .
WEI Q , TU Y Z , ZUO L , et al . miR-345-3p attenuates apoptosis and inflammation caused by oxidized low-density lipoprotein by targeting TRAF6 via TAK1/p38/NF-κB signaling in endothelial cells [J ] . Life Sci , 2020 , 241 : 117142 .
DAI Y , YI X L , HUANG Y H , et al . miR-345-3p modulates M1/M2 macrophage polarization to inhibit inflammation in bone infection via targeting MAP3K1 and NF-κB pathway [J ] . J Immunol , 2024 , 212 ( 5 ): 844 - 854 .
MI H Y , HUANG X S , MURUGANUJAN A , et al . PANTHER version 11:expanded annotation data from gene ontology and reactome pathways,and data analysis tool enhancements [J ] . Nucleic Acids Res , 2017 , 45 ( D1 ): D183 - D189 .
DU N , LIN H M , ZHANG A Q , et al . N-phenethyl-5-phenylpicolinamide alleviates inflammation in acute lung injury by inhibiting HIF-1α/glycolysis/ASIC1a pathway [J ] . Life Sci , 2022 , 309 : 120987 .
QIAN F H , HE S C , YANG X M , et al . Circular RNA DHTKD1 targets miR-338-3p/ETS1 axis to regulate the inflammatory response in human bronchial epithelial cells [J ] . Exp Ther Med , 2023 , 26 ( 1 ): 316 .
谢淑敏 , 郭淑杰 , 薛丙权 , 等 . 基于树突细胞外泌体miRNA探究人参皂苷Rg 1 改善慢性阻塞性肺疾病的作用机制 [J ] . 中国医院药学杂志 , 2025 , 45 ( 10 ): 1140 - 1146 .
ZHANG J H , TIAN W Y , WANG F , et al . Advancements in understanding the role of microRNAs in regulating macrophage polarization during acute lung injury [J ] . Cell Cycle , 2023 , 22 ( 14/15/16 ): 1694 - 1712 .
丁晓彦 , 林志军 , 王岱 . 金银花-连翘药对的成分和药理作用研究进展 [J ] . 山东科学 , 2019 , 32 ( 3 ): 36 - 41 .
HUANG J J , XIA J , HUANG L L , et al . HIF-1α promotes NLRP3 inflammasome activation in bleomycin-induced acute lung injury [J ] . Mol Med Rep , 2019 , 20 ( 4 ): 3424 - 3432 .
ECKLE T , BRODSKY K , BONNEY M , et al . HIF1A reduces acute lung injury by optimizing carbohydrate metabolism in the alveolar epithelium [J ] . PLoS Biol , 2013 , 11 ( 9 ): e1001665 .
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