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hucMSC 条件培养基通过抑制 Nrf2/NF-κB 信号通路减轻脂多糖诱导的急性肺损伤及其氧化应激和炎症反应。

hucMSC Conditioned Medium Ameliorate Lipopolysaccharide-Induced Acute Lung Injury by Suppressing Oxidative Stress and Inflammation via Nrf2/NF-B Signaling Pathway.

机构信息

Department of Cardiothoracic Surgery; Ministry of Education Key Laboratory of Child Development and Disorders; National Clinical Research Center for Child Health and Disorders; China International Science and Technology Cooperation Base of Child Development and Critical Disorders, Children's Hospital of Chongqing Medical University, Chongqing, China.

Chongqing Key Laboratory of Pediatrics; Chongqing Engineering Research Center of Stem Cell Therapy, Chongqing Medical University, Chongqing, China.

出版信息

Anal Cell Pathol (Amst). 2021 Aug 13;2021:6653681. doi: 10.1155/2021/6653681. eCollection 2021.

Abstract

Acute lung injury (ALI) is a common clinical syndrome in the cardiac intensive care unit with a high mortality rate. Inflammation and oxidative stress have been reported to play a crucial role in the development of ALI. Previous studies have shown that human umbilical cord mesenchymal stem cells (hucMSCs) have anti-inflammatory and antioxidative effects in various diseases. However, the anti-inflammatory and antioxidative effects of the hucMSC conditioned medium (CM) on LPS-induced ALI remain unclear. Therefore, in this study, we assessed whether the hucMSC conditioned medium could attenuate LPS-induced ALI and the underlying mechanisms. Mice were randomly divided into four groups: the control group, PBS group, LPS+PBS group, and LPS+CM group. The lung histopathology and bronchoalveolar lavage fluid (BALF) were analyzed after intervention. The Nrf2/NF-B signaling pathway and its downstream target genes were tested, and the cytokines and growth factors in CM were also measured. The results showed that CM significantly attenuated the histological alterations; decreased the wet/dry weight ratio; reduced the levels of MPO, MDA and ROS; increased SOD and GSH activity; and downregulated the level of proinflammatory cytokines such as IL-1, IL-6, and TNF-. Furthermore, CM promoted the expression of Nrf2 and its target genes NQ01, HO-1, and GCLC and inhibited the expression of NF-B and its target genes IL-6, IL-1, and TNF-. These effects may be closely related to the large amounts of cytokines and growth factors in the CM. In conclusion, our results demonstrated that CM could attenuate LPS-induced ALI, probably due to inhibition of inflammation and oxidative stress via the Nrf2/NF-B signaling pathway.

摘要

急性肺损伤(ALI)是心脏重症监护病房常见的临床综合征,死亡率较高。炎症和氧化应激被报道在 ALI 的发展中起关键作用。先前的研究表明,人脐带间充质干细胞(hucMSCs)在各种疾病中具有抗炎和抗氧化作用。然而,hucMSC 条件培养基(CM)对 LPS 诱导的 ALI 的抗炎和抗氧化作用尚不清楚。因此,在这项研究中,我们评估了 hucMSC 条件培养基是否可以减轻 LPS 诱导的 ALI 及其潜在机制。小鼠被随机分为四组:对照组、PBS 组、LPS+PBS 组和 LPS+CM 组。干预后分析肺组织病理学和支气管肺泡灌洗液(BALF)。检测 Nrf2/NF-B 信号通路及其下游靶基因,并测量 CM 中的细胞因子和生长因子。结果表明,CM 显著减轻组织学改变;降低湿/干重比;降低 MPO、MDA 和 ROS 水平;增加 SOD 和 GSH 活性;下调促炎细胞因子如 IL-1、IL-6 和 TNF-α的水平。此外,CM 促进了 Nrf2 及其靶基因 NQ01、HO-1 和 GCLC 的表达,并抑制了 NF-B 及其靶基因 IL-6、IL-1 和 TNF-α的表达。这些作用可能与 CM 中大量的细胞因子和生长因子密切相关。总之,我们的结果表明,CM 可以减轻 LPS 诱导的 ALI,可能是通过 Nrf2/NF-B 信号通路抑制炎症和氧化应激所致。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/195d/8380155/478594712e3c/ACP2021-6653681.001.jpg

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