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Effects Of Telmisartan On THP-1Foam Cells Source ABCA1and ABCG1Expression And Cholesterol Efflux

Posted on:2015-01-23Degree:MasterType:Thesis
Country:ChinaCandidate:Q RanFull Text:PDF
GTID:2254330431963655Subject:Cardiovascular medicine
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Objective:To investigate the effect of telmisartan on THP-1derived foam cells in ABCA1, mRNA and ABCG1protein expression and cholesterol efflux, clear effect of telmisartan in anti atherosclerosis, and provide a theoretical basis for the prevention and treatment of atherosclerosis.Method:1. Cultured THP-1monocytes by PMA induced to differentiate into macrophages by CD68immunohistochemical staining of macrophages.2. Preparation of foam cell model for dealing with OX-LDL macrophages, oil red O staining lipid identification in foam cells.3. Different concentrations of telmisartan solution (0.1,1.0,10.0ummol/L) were added to the model in foam cells co-cultured48h, the extraction of total RNA and protein in each cell.4. Measured in each group ABCA1mRNA, ABCG1mRNA. Using real-time quantitative RT-PCR technique.5. Determination of ABCA1, ABCG1protein were expressed by Western Blot technology.6. Added to a final concentration of cells in each group was50umol/dL of apoA-I or HDL co-cultured24h, the determination of intracellular cholesterol content by HPLC. 7. Statistical analysis, Measurement data representation with x±s,comparison between groups of the same indicator analysis of variance, pairwise comparisons between groups SNK test applied to P<0.05was considered statistically significant.Result:1. After PMA-induced THP-1cells after the CD68antigen on immunohistochemical staining was positive, which means that differentiate into macrophages, macrophages, and then after the role of ox-LDL, oil red O staining bright red lipid droplets in cells, which means the success of differentiated macrophage foam cells. Figure1, Figure2, Figure3.2. Different concentrations of telmisartan (0.1,1.0,10.0ummol/L) of foam cells intervention can promote the expression of ABCAl, ABCG1mRNA expression and protein.①with the control group (1.000±0.012) compared to, ABCAlmRNA expression telmisartan concentration1.0umol/1group ABCA1mRNA expression (1.301±0.028) and telmisartan concentration10.0umol/1group (1.502±0.012),(P<0.05), a significant difference, and in a concentration-dependent manner.②with the control group (1.000±0.042) compared with telmisartan concentration1.0umol/1group ABCG1mRNA expression (1.287±0.032), and telmisartan concentration10.Oumol/1group ABCG1mRNA expression (1.486±0.009),(P <0.05), statistically significant and dose-dependent.③with the control group (0.998±0.053) compared with telmisartan concentration1.0umol/1group ABCAl protein expression (1.288±0.056) and telmisartan concentration10.0umol/1group ABCA1protein expression (1.489±0.049),(P<0.05), statistically significant and dose-dependent.④with the control group (0.995±0.040) compared with telmisartan concentration1.0umol/1group ABCG1protein expression (1.279±0.019), and telmisartan concentration10.0umol/1histone expression (1.454±0.230),(P<0.05), statistically significant and dose-dependent. 3. Telmisartan or apoA-I in HDL mediated lipid droplet formation can be reduced within the foam cells, the intracellular cholesterol levels to reduce (P<0.05).①apoA-I mediated in the control group total cholesterol (430±40) and free cholesterol (170±20) compared to concentrations of telmisartan1.0umol/1Total cholesterol levels (326±23) and free cholesterol levels (123±17), telmisartan concentration10.0umol/1group, the total cholesterol levels (263±24) and free cholesterol levels (117±12),(P<0.05), there are significant differences, and has concentration-dependent manner. HDL mediates②In comparison with the control group, the total cholesterol (403±33) and free cholesterol (160±22), telmisartan concentration1.0umol/1Total cholesterol levels (270±26) and free cholesterol levels (114±23), telmisartan concentration10.0umol/1group, the total cholesterol levels (237±21) and free cholesterol levels (95±16),(P<0.05), there are significant differences, and has a concentration dependence.Conclusion:1.Telmisartan promotes the expression of ABCA1, ABCG1at mRNA and protein levels in a concentration dependent manner.2. Telmisartan in apoA-I or HDL-mediated intracellular cholesterol can reduce cholesterol efflux to promote.
Keywords/Search Tags:Atherosclerosis, reverse cholesterol transport, ABCA1, ABCG1, telmisartan
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