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The Role Of Hydrogen In The Regulation Of Atherosclerotic Inflammatory Response And The Expression Of Related MicroRNAs

Posted on:2023-02-03Degree:MasterType:Thesis
Country:ChinaCandidate:X J LiuFull Text:PDF
GTID:2544307073484504Subject:Pharmacy
Abstract/Summary:PDF Full Text Request
Atherosclerosis is a common pathological basis of cardiovascular and cerebrovascular diseases,and it is a chronic inflammatory disease.Micro RNAs(miRNAs)are involved in the occurrence and development of atherosclerosis,among which the anti-inflammatory gene miRNA-146 a inhibits nuclear factor κB by targeting the expression of IRAK1 and TRAF6,and miRNA-181 b by targeting the expression of importin-α3 Activation of the(nuclear factor kappa-B,NF-κB)signaling pathway,the pro-inflammatory gene miRNA-92 a aggravates the inflammatory response.They affect the function of cells by regulating the expression of downstream target genes in endothelial cells,smooth muscle cells and macrophages,and ultimately affect the progression of atherosclerosis.Moreover,studies have found that the expression of these three miRNAs is significantly different between normal and atherosclerotic humans.In patients with atherosclerosis,the anti-inflammatory genes miRNA-146 a and miRNA-181 b were down-regulated,and the pro-inflammatory gene miRNA-92 a was up-regulated.By regulating the expression of inflammatory response-related miRNAs,the disease process can be significantly inhibited.Hydrogen has anti-inflammatory,anti-oxidative,anti-apoptotic,regulating miRNAs expression and other effects,and has high biological safety,and can play a good synergistic effect with a variety of drugs.While ensuring the prospect of clinical application,it can effectively avoid complications in clinical application.Therefore,this paper aims to study the role of hydrogen in the inflammatory response of three types of atherosclerosis-related cells and the expression of miRNAs(miRNA-146 a,miRNA-181 b,miRNA-92a),and to explore the role of hydrogen at the cellular and molecular levels.The role of hydrogen in atherosclerotic disease provides a basis and reference for further research.Compared with the traditional method of repeatedly replacing the hydrogen-rich medium,this paper prepares a hydrogen-rich culture system that can provide stable hydrogen concentration for a long time according to the patent.On this basis,this paper further explores the application prospects of hydrogen in atherosclerosis.In the pathological process of atherosclerosis,due to persistent inflammation at the lesion site,endothelial cell damage,smooth muscle cell phenotype transformation,and macrophage release of inflammatory factors will occur.Therefore,in this paper,endothelial cells,smooth muscle cells and macrophages were modeled by lipopolysaccharide(LPS),and then cultured in a hydrogen-rich culture system.The cell apoptosis was detected by flow cytometry.Hydrogen had a good anti-apoptosis effect on endothelial cells.The expressions of vascular cell adhesion molecule-1(VCAM-1)and intercellular cell adhesion molecule-1(ICAM-1)were detected by q PCR and ELISA,which proved that hydrogen can reduce the Adhesion molecules secreted by endothelial cells in the inflammatory state play a certain therapeutic role in the early inflammatory response of atherosclerosis.α-smooth muscle actin(α-SMA)was detected by immunofluorescence,and α-SMA,myosin heavy chain 11(myosin heavy chain 11,myosin heavy chain 11,MYH11)and disregulated protein 1(spinocerebellar ataxia type 1,SCA1)were detected,and it was proved that hydrogen can inhibit the transition of lipopolysaccharide-induced smooth muscle phenotype to secretory type.Using q PCR and ELISA to detect inflammatory factors in macrophages,it was proved that hydrogen could reduce the expression of the pro-inflammatory factors interleukin 6(IL-6)and tumor necrosis factor-α(TNF-α)in LPS-induced macrophages,increased the expression of the anti-inflammatory factor Transforming growth factor beta 1(TGF-β1).Moreover,hydrogen could increase the expression of anti-inflammatory genes miRNA-146 a and miRNA-181 b,and reduce the expression of pro-inflammatory gene miRNA-92 a in all three kinds of cells.In conclusion,this paper aims to explore the role of hydrogen in the inflammatory response of atherosclerosis and the expression of related miRNAs,and to demonstrate the potential of hydrogen in the treatment of atherosclerosis at the cytological level.
Keywords/Search Tags:Hydrogen, Hydrogen-rich culture system, Atherosclerosis, Molecular biology, inflammation
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