Dissertation > Excellent graduate degree dissertation topics show

The Inhibitory Effect of Silencing Cx43 Gene by RNAi on Vascular Restenosis

Author: ChenMin
Tutor: JiangLiPing
School: Nanchang University
Course: Pharmacology
Keywords: Lentiviral RNA interference Connexin 43 Vascular restenosis
CLC: R541.4
Type: Master's thesis
Year: 2011
Downloads: 25
Quote: 0
Read: Download Dissertation

Abstract


Background: Percutaneous transluminal coronary interventional procedures (percutaneous transluminal coronary intervention, PCI) is one of the coronary artery disease, the main treatment measures, however, PCI restenosis after angioplasty (restenosis, RS) high The incidence of a serious impact to its therapeutic effect. Therefore, to clarify the mechanism of vascular RS, and to find effective treatments become a major difficulty of the field of cardiovascular pharmacological studies with hot. Gap junctions between adjacent cells (gap junction, GJ) inorganic ion exchange direct channel for small molecules the substance (lt; 1kDa) and cellular metabolites. Studies have shown that there is a wide range of gap junctions networks vessel wall can feel the cavity internal and external stimulation and to make the overall reaction, vascular lesions gap junction proteins (connexins, Cxs) reconstruction. We assume that the Cx43 remodeling may be involved in the pathological process of vascular RS, to silence Cx43 gene expression may inhibit vascular RS new theoretical and targets, and thus provide for the prevention and treatment of vascular RS. Objective: To clarify the correlation of Cx43 remodeling and vascular RS, by RNA interference (ribonucleic acid interfering RNAi) technology silence Cx43 gene, vascular RS inhibition observed in the overall model. Lay the theoretical foundation for the development of new carrier gene bracket pre-clinical studies of the treatment of RS. Methods: 24 SD rats were randomly divided into four groups (n = 6): sham group, model group, Cx43-RNAi-LV treatment group and NC-GFP-LV group. In addition to the sham group, the other three groups of the left common carotid artery underwent balloon injury of surgery, postoperative 100μL saline were injected into of Cx43-RNAi-LV and NC-GFP-LV to the carotid artery at 37 ℃ incubated for 1h, the the slow virus titer of 5 × 108TU/mL. The the postoperative 28d rats were sacrificed to take the left common carotid artery alternate inverted fluorescence microscope to observe the efficiency of lentiviral infection; the HE stained determination vascular morphology; immunohistochemical observation Cx43 protein expression and distribution; Western Blotting detection Cx43 protein expression. Results: inverted fluorescence microscope: sham group and model group were not found in the the fluorescence, Cx43-RNAi-LV treatment group and the NC-of GFP-the LV group neointimal and medial observed to a large number of fluorescent, indicating the success of lentiviral infection neck artery. HE staining showed that: compared with the sham group, postoperative the 28d model for group and NC-GFP-LV group the new endometrium was significantly thicker, neointimal area / medial area (neointima area / media area, NA / MA) a significant increase (p lt; 0.01) shows that the successful establishment of vascular RS model. Compared with the model group, neointimal hyperplasia of Cx43-RNAi-LV treatment group significantly reduced NA / MA value significantly lower (P lt; 0.05) prompts Cx43-RNAi-LV has a significant inhibitory effect on vascular RS. The immunohistochemical observation Show: four groups of rat vascular smooth muscle cells were positive for Cx43 expression. The endometrium was significantly thicker compared with the sham group, postoperative the 28d model for group and NC-GFP-LV group of Cx43 protein expression increased density. Compared with model group, the treatment group of Cx43-RNAi-LV Cx43 protein expression density was significantly reduced, suggesting that Cx43 refactoring involved in the pathological process of vascular RS. Western Blotting detection results: Compared with the sham group, postoperative the 28d model for group and NC-GFP-LV group Cx43 protein expression was significantly increased (P lt; 0.01). Compared with the model group, Cx43 protein expression of Cx43-RNAi-LV treatment group was significantly reduced (p lt; 0.05), prompted Cx43-RNAi-LV inhibited vascular Cx43 protein expression after balloon injury. Conclusion: ① The of Cx43 protein refactoring involved in vascular RS pathological process; ② The of Cx43-of RNAi-LV can significantly with suppression after balloon injury in vascular Cx43 protein high expression; ③ The of Cx43-of RNAi-LV can significantly with inhibition of rat carotid total artery balloon injury-induced vascular RS.

Related Dissertations

  1. Expression Dynamics of Pheromone Binding Proteins and Expression Influences by Mating and Knockdown of Cryl in Spodoptera Exigua,S433.4
  2. Molecular Cloning, Mrna Expression and Rnai of Nadph-Cytochrome P450 Reductase Gene in Helicoverpa Armigera (Hǘbner),S435.622.3
  3. Effects of BMPR-IB Gene Silencing by Small Interfering RNA on Apoptosis of Porcine Pollicular Granulosa Cells and Ecpression of BMP Pathy-Way-Ralted Genes,S828
  4. Inhibition of Myostatin (MSTN) Expresstion in Primary Porcine Fetal Fibroblasts by Lentivector-mediated RNAi,S828
  5. The DNA Cloning and RNA Interference of Some Functional Genes in Laodelphax Striatellus (Fallen),S435.112.3
  6. The Effect of RNA Interference-mediated ERCC1 Gene on the Chemo-treatment Sensitivity of NSCLC in Vitro,R734.2
  7. The Study of Inhibtion Effect by shRNA Expression Vector on Herpes Simplex Virus Type 2 UL54,R346
  8. The Functions of Chitinase Genes from Locusta Migratoria,S433.2
  9. The Effect of Silencing Spl Gene on Expression of CD59 in Prostate Cancer Cell by RNA Interference,R737.25
  10. Construction of Silence Vector for Cytochrome b Gene in Nucleus of Arabidopsis Thaliana and the Transformation,Q943
  11. Construction and Identification of the Recombinant Lentiviral Vector Expressing p55PIK,R373
  12. Construction of RNA Interference Vectors of Pin Genes Determining Grain Hardness and Genetic Transformation in Wheat,S512.1
  13. An Experimental Study of Inhibition the Expression of Ppif Gene Reduce Renal Ischemia-reperfusion Injury in Rats,R363
  14. Expression of the POU Domain Transcription Factor Oct4 in Human Transitional Carcinoma Tissue of Bladder and Its Effects on the Biological Behavior of Human Bladder Cancer Cell Line EJ,R737.14
  15. Silencing of SOCS1 Enhances Dc-mediated Anti-laryngocarcinoma Immunity,R739.65
  16. Research of Damage Efficiency by Livin/Survivin RNA Interference on Colorectal Cancer Cell Mediated by mPEGylated-chitosan Nanoparticles,R735.34
  17. Construction and Identification of MicroRNA Eukaryotic Expression Vectors Targeting Vsacular Endothelial Growth Factor,R735.7
  18. Inhibition of SH-SY5Y Cell Growth by TMEFF2 Gene,Q343
  19. Study on Gene Therapy of SiRNA Targeted at Telomerase of Hepatocellular Carcinoma Transduced by Lentivirus in Vitro,R735.7
  20. Expression and Clinical Significance of Connexin 43 in Bladder Urothelial Carcinoma,R737.14
  21. Cloning Expression and Functional Analysis of a Endoplasmic Reticulum Resident Glyprotein, KDELC1,R735.7

CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Coronary arteries ( atherosclerosis ),heart disease (CHD)
© 2012 www.DissertationTopic.Net  Mobile