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Propofol Regulates the TLR4/NF-κB Pathway Through miRNA-155 to Protect Colorectal Cancer Intestinal Barrier.
- Source :
-
Inflammation [Inflammation] 2021 Oct; Vol. 44 (5), pp. 2078-2090. Date of Electronic Publication: 2021 Jun 03. - Publication Year :
- 2021
-
Abstract
- Surgery for colorectal cancer (CRC) can cause damage to the intestinal mucosal barrier and lead to bacterial invasion. This study mainly analyzed whether propofol (PPF) could protect the intestinal mucosal barrier damage caused by CRC surgery, and explored its molecular mechanism. A mouse CRC model was constructed using azomethane and dextran sulfate sodium. During anesthesia, continuous intravenous injection of PPF was used for intervention. The influences of PPF on intestinal mucosal permeability and bacterial invasion were detected. The levels of microRNA (miR)-155, Toll-like receptor 4 (TLR4)/NF-κB in the intestinal mucosa, and the location of miR-155 were detected by fluorescence in situ hybridization (FISH). Mouse macrophages were used to analyze the regulation of miR-155 on the secretion of inflammatory cytokines through the TLR4/NF-κB pathway. PPF treatment promoted the expression of tight junction protein in the intestinal mucosa, protected the intestinal barrier, inhibited the translocation of intestinal bacteria, and increased the level of the beneficial bacterium Lactobacillus on the mucosal surface. In addition, PPF treatment could inhibit the expression of miR-155, TLR4/NF-KB, and reverse inflammatory response. miR-155 was expressed in macrophages of intestinal mucosa tissue. Overexpression of miR-155 promoted the nuclear translocation of NF-κB and the expression of inflammatory cytokines in macrophages. The use of VIPER to inhibit TLR4 reversed the pro-inflammatory effects of miR-155. PPF might inhibit the activation of the NF-κB pathway by downregulating miR-155 expression, thereby reducing the secretion of inflammatory cytokines. This might be the mechanism by which PPF protected the intestinal barrier of CRC surgical model mice.<br /> (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Subjects :
- Animals
Colorectal Neoplasms drug therapy
Colorectal Neoplasms pathology
Hypnotics and Sedatives pharmacology
Hypnotics and Sedatives therapeutic use
Inflammation Mediators antagonists & inhibitors
Inflammation Mediators metabolism
Intestinal Mucosa drug effects
Intestinal Mucosa pathology
Male
Mice
Mice, Inbred C57BL
MicroRNAs metabolism
NF-kappa B metabolism
Propofol pharmacology
RAW 264.7 Cells
Signal Transduction drug effects
Signal Transduction physiology
Toll-Like Receptor 4 metabolism
Colorectal Neoplasms metabolism
Intestinal Mucosa metabolism
MicroRNAs antagonists & inhibitors
NF-kappa B antagonists & inhibitors
Propofol therapeutic use
Toll-Like Receptor 4 antagonists & inhibitors
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2576
- Volume :
- 44
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 34081253
- Full Text :
- https://doi.org/10.1007/s10753-021-01485-0