Department of Gastrointestinal Surgery, First Affiliated Hospital of Dali University, Dali City, China.
Department of Emergency, 36657The First Hospital Affiliated of Kunming Medical University, Kunming, China.
Innate Immun. 2022 Jan;28(1):19-36. doi: 10.1177/17534259211068744.
Notoginsenoside R1 (NG-R1), the extract and the main ingredient of has anti-inflammatory effects and can be used in treating acute lung injury (ALI). In this study, we explored the pulmonary protective effect and the underlying mechanism of the NG-R1 on rats with ALI induced by severe acute pancreatitis (SAP). MiR-128-2-5p, ERK1, Tollip, HMGB1, TLR4, IκB, and NF-κB mRNA expression levels were measured using real-time qPCR, and TLR4, Tollip, HMGB1, IRAK1, MyD88, ERK1, NF-κB65, and P-IκB-α protein expression levels using Western blot. The NF-κB and the TLR4 activities were determined using immunohistochemistry, and TNF-α, IL-6, IL-1β, and ICAM-1 levels in the bronchoalveolar lavage fluid (BALF) using ELISA. Lung histopathological changes were observed in each group. NG-R1 treatment reduced miR-128-2-5p expression in the lung tissue, increased Tollip expression, inhibited HMGB1, TLR4, TRAF6, IRAK1, MyD88, NF-κB65, and p-IκB-α expression levels, suppressed NF-κB65 and the TLR4 expression levels, reduced MPO activity, reduced TNF-α, IL-1β, IL-6, and ICAM-1 levels in BALF, and alleviated SAP-induced ALI. NG-R1 can attenuate SAP-induced ALI. The mechanism of action may be due to a decreased expression of miR-128-2-5p, increased activity of the Tollip signaling pathway, decreased activity of HMGB1/TLR4 and ERK1 signaling pathways, and decreased inflammatory response to SAP-induced ALI. Tollip was the regulatory target of miR-128-2-5p.
Notoginsenoside R1 (NG-R1) 是提取物和主要成分，具有抗炎作用，可用于治疗急性肺损伤（ALI）。在这项研究中，我们探讨了 NG-R1 对重症急性胰腺炎（SAP）诱导的 ALI 大鼠的肺保护作用及其潜在机制。使用实时 qPCR 测量 miR-128-2-5p、ERK1、Tollip、HMGB1、TLR4、IκB 和 NF-κB mRNA 表达水平，使用 Western blot 测量 TLR4、Tollip、HMGB1、IRAK1、MyD88、ERK1、NF-κB65 和 P-IκB-α 蛋白表达水平。使用免疫组织化学测定 NF-κB 和 TLR4 的活性，使用 ELISA 测定支气管肺泡灌洗液（BALF）中的 TNF-α、IL-6、IL-1β 和 ICAM-1 水平。观察各组的肺组织病理学变化。NG-R1 治疗降低了肺组织中的 miR-128-2-5p 表达，增加了 Tollip 表达，抑制了 HMGB1、TLR4、TRAF6、IRAK1、MyD88、NF-κB65 和 p-IκB-α 的表达水平，抑制了 NF-κB65 和 TLR4 的表达水平，降低了 MPO 活性，降低了 BALF 中的 TNF-α、IL-1β、IL-6 和 ICAM-1 水平，并缓解了 SAP 诱导的 ALI。NG-R1 可减轻 SAP 诱导的 ALI。作用机制可能是由于 miR-128-2-5p 表达降低，Tollip 信号通路活性增加，HMGB1/TLR4 和 ERK1 信号通路活性降低，以及 SAP 诱导的 ALI 炎症反应减轻。Tollip 是 miR-128-2-5p 的调节靶点。
