叶麻珠通过调节 Toll 样受体 4/核因子-κB/核苷酸结合寡聚化结构域样受体家族含 pyrin 结构域蛋白 3 信号通路改善脂多糖诱导的大鼠急性肺损伤和肠道菌群失调。
Yemazhui () ameliorates lipopolysaccharide-induced acute lung injury modulation of the toll-like receptor 4/nuclear factor kappa-B/nod-like receptor family pyrin domain-containing 3 protein signaling pathway and intestinal flora in rats.
机构信息
Chongqing Key Laboratory of Traditional Chinese Medicine for Prevention and Cure of Metabolic Diseases, College of Traditional Chinese Medicine, Chongqing Medical University, Chongqing 400016, China.
College of Basic Medicine, Chongqing Medical University, Chongqing 400016, China.
出版信息
J Tradit Chin Med. 2024 Apr;44(2):303-314. doi: 10.19852/j.cnki.jtcm.20230510.001.
OBJECTIVE
To investigate the impact of Yemazhui (, HEL) against lipopolysaccharide (LPS)-induced acute lung injury (ALI) and explore its underlying mechanism .
METHODS
The chemical constituents of HEL were analyzed by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method. Then, HEL was found to suppress LPS-induced ALI . Six-week-old male Sprague-Dawley rats were randomly divided into 6 groups: control, LPS, Dexamethasone (Dex), HEL low dose 6 g/kg (HEL-L), HEL medium dose 18 g/kg (HEL-M) and HEL high dose 54 g/kg (HEL-H) groups. The model rats were intratracheally injected with 3 mg/kg LPS to establish an ALI model. Leukocyte counts, lung wet/dry weight ratio, as well as myeloperoxidase (MPO) activity were determined followed by the detection with hematoxylin and eosin staining, enzyme linked immunosorbent assay, quantitative real time polymerase chain reaction, western blotting, immunohistochemistry, and immunofluorescence. Besides, to explore the effect of HEL on ALI-mediated intestinal flora, we performed 16s rRNA sequencing analysis of intestinal contents.
RESULTS
HEL attenuated LPS-induced inflammation in lung tissue and intestinal flora disturbance. Mechanism study indicated that HEL suppressed the lung coefficient and wet/dry weight ratio of LPS-induced ALI in rats, inhibited leukocytes exudation and MPO activity, and improved the pathological injury of lung tissue. In addition, HEL reduced the expression of tumor necrosis factor-alpha, interleukin-1beta (IL-1β) and interleukin-6 (IL-6) in bronchoalveolar lavage fluid and serum, and inhibited nuclear displacement of nuclear factor kappa-B p65 (NF-κBp65). And 18 g/kg HEL also reduced the expression levels of toll-like receptor 4 (TLR4), myeloid differentiation factor 88, NF-κBp65, phosphorylated inhibitor kappa B alpha (phospho-IκBα), nod-like receptor family pyrin domain-containing 3 protein (NLRP3), IL-1β, and interleukin-18 (IL-18) in lung tissue, and regulated intestinal flora disturbance.
CONCLUSIONS
In summary, our findings revealed that HEL has a protective effect on LPS-induced ALI in rats, and its mechanism may be related to inhibiting TLR4/ NF-κB/NLRP3 signaling pathway and improving intestinal flora disturbance.
目的
研究叶下珠（HEL）对脂多糖（LPS）诱导的急性肺损伤（ALI）的影响，并探讨其作用机制。
方法
采用超高效液相色谱-四极杆飞行时间质谱联用技术分析 HEL 的化学成分。然后发现 HEL 能抑制 LPS 诱导的 ALI。将 6 周龄雄性 Sprague-Dawley 大鼠随机分为 6 组：对照组、LPS 组、地塞米松（Dex）组、HEL 低剂量 6 g/kg（HEL-L）组、HEL 中剂量 18 g/kg（HEL-M）组和 HEL 高剂量 54 g/kg（HEL-H）组。通过气管内注射 3mg/kg LPS 建立 ALI 模型。随后通过苏木精和伊红染色、酶联免疫吸附试验、实时定量聚合酶链反应、Western blot、免疫组织化学和免疫荧光检测白细胞计数、肺湿/干重比以及髓过氧化物酶（MPO）活性。此外，为了探讨 HEL 对 ALI 介导的肠道菌群的影响，我们对肠道内容物进行了 16s rRNA 测序分析。
结果
HEL 减轻了 LPS 诱导的肺组织炎症和肠道菌群失调。机制研究表明，HEL 抑制了 LPS 诱导的 ALI 大鼠的肺系数和湿/干重比，抑制了白细胞渗出和 MPO 活性，改善了肺组织的病理损伤。此外，HEL 降低了支气管肺泡灌洗液和血清中肿瘤坏死因子-α、白细胞介素-1β（IL-1β）和白细胞介素-6（IL-6）的表达，并抑制了核因子 kappa-B p65（NF-κBp65）的核移位。18 g/kg HEL 还降低了肺组织中 toll 样受体 4（TLR4）、髓样分化因子 88、NF-κBp65、磷酸化抑制κB 亚单位α（phospho-IκBα）、核苷酸结合寡聚结构域样受体家族包含pyrin 结构域 3 蛋白（NLRP3）、IL-1β 和白细胞介素-18（IL-18）的表达水平，并调节肠道菌群失调。
结论
综上所述，我们的研究结果表明，HEL 对 LPS 诱导的大鼠 ALI 具有保护作用，其机制可能与抑制 TLR4/NF-κB/NLRP3 信号通路和改善肠道菌群失调有关。
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