Abstract
The purpose of this study was to explore the investigative mechanism of salidroside (SAL) on LPS-induced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). The exosomes from RLE-6TN are extracted and identified by transmission electron microscopy, particle size analysis and protein marker detection, and co-cultured with NR8383 cells. The ALI/ARDS model of SD rats was established by LPS (10 mg/kg) intratracheal instillation. Following a four-hour intratracheal instillation of LPS, 50 μl of RLE-6TN exosomes were injected through the tail vein. After that, SAL and miR-146a antagomir were injected into the tail vein for 72 h, respectively. As the changes of HE stain, body weight and ALI score are observed. The expression of miR-146a, TLR4, NF-kB, IRAK1, TRAF6 and their related proteins were detected by RT-PCR and Western blot, respectively. TNF-α, IL-6, IL-8 and IL-1 β inflammatory factors were detected by ELISA. The expression of miR-146a, NF-kB, IRAK, TRAF6 and related inflammatory factors in LPS-induced NR8383 was significantly higher than that in the control group, while SAL has greatly reduced the expression of TLR4 mediated NF-kB inflammatory pathway and related inflammatory factors. SAL can significantly improve the LPS-induced lung morphological abnormalities, slowed down the rate of weight loss in rats, and reducing the ALI score. The expression trend of NF-kB, IRAK, TRAF6 and related inflammatory factors in rats’ lung tissues was consistent with that in NR8383 cells. SAL has a protective effect on ALI/ARDS caused by sepsis, which is likely to be developed to a potential treatment for the disease. To sum up, this study provides a new theoretical basis for the treatment of ALI/ARDS with SAL.
Highlights
The purpose of this study was to explore the investigative mechanism of salidroside (SAL) on LPSinduced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS)
Guan et al believe that SAL has a protective effect on ALI/ARDS induced by lipopolysaccharide (LPS) in a nimals[12]
By targeting miRNA related to inflammation it may serve as a new and effective method to treat ALI/ARDS caused by sepsis
Summary
The purpose of this study was to explore the investigative mechanism of salidroside (SAL) on LPSinduced acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). SAL has a protective effect on ALI/ARDS caused by sepsis, which is likely to be developed to a potential treatment for the disease. Recent studies show that miR-146a can regulate the inflammatory response of THP-1 cells (human monocytes)[8,9]. It can negatively regulate the expression of TLR4 pathway related molecules and downstream inflammatory factors. Exosomes are nano particles (< 100 nm) secreted by cells, which can effectively deliver miRNA to receptor cells They are gradually used as research methods to explore new therapeutic strategies and drug delivery vehicles. It is of great significance to explore the role of exosomes in the delivery of miR-146a to AM and the regulation of inflammatory response
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