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The Effect Of Adiponectin On Reverse Cholesterol Transport In APN-/- Mice Macrophages And Its Mechanism

Posted on:2016-10-24Degree:MasterType:Thesis
Country:ChinaCandidate:Y Y GuoFull Text:PDF
GTID:2284330479992490Subject:Internal medicine
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Objective:To study the effect of the Adiponectin on reverse cholesterol transport in mice macrophages,anti-atherosclerosis and its mechanism.Methods:1.ModelThirty adiponectin knocked out mice were fed with high-fat chow for the induction of atherosclerosis.2. GroupingThe thirty adiponectin knocked out mice were randomly divided into five groups:control group,50μg/(kg· d)probucol treatment group,150μg/(kg· d)probucol treatment group,200μg/(kg· d)probucol treatment group and250μg/(kg· d).3. Experimental methodsAfter APN probucol treatment four weeks,the mice were injected with acetylented LDL and 3H-TC-labled RAW264.7 macrophage.We use enzymatic methed to measure their serum lipoid level.We use liquid scintillation counter to measure the proportion of intraperitioneally injected 3H-TC in liver tissues,in serum and feces.Then determined for transcription levels of ABCA1 m RNA by RT-PCR,for the expression of ABCA1 proteins by Western-blot.Results:1. Compared with control group,the serum TC,HDL-C,LDL-C was significantly lower and HDL was higher in different probucol treatment groups after four weeks of adiponectin intervention(P<0.05,P<0.1).This effect were dose-dependent.2. In the control group aortic atherosclerotic lesions was significantly.Light microscopy showed a large number of lipid deposition in the vessel wall, there is plaque formation, with scattered foam cells; Use adiponectin intervention group aortic atherosclerosis light hardening.3.The 3H-TC level was significantly lower in serum(P<0.05)and higher in liver and feces(P<0.05).4.Detected by RT-PCR, the intervention of APN significantly increased the m RNA of the ABCA1 in liver tissues,and this effects were dose-dependent increase(P<0.05).5.Detected by Western-blot, the intervention of APN significantly increased the protein of the ABCA1 in liver tissues,and this effects were dose-dependent increase(P<0.05).Conclusion:1. Adiponectin can reduce serum TC, TG and LDL levels, increase HDL;2. Adiponectin can reduced the aortic atherosclerosis in mice.3. Adiponectin can increase cholesterol efflux rate in serum, liver and feces.4. Adiponectin can upregulate the levels of m RNA and protein expression of ABCA1,this effects were dose-dependent. Adiponectin promoted reverse cholesterol transport by increasing ABCA1 m RNA levels and the expression of its protein,promotes cellular cholesterol efflux,delayed the occurrence and development of atherosclerosis.It provides a new idea for the preventiong and treatment of cardiovascular disease.
Keywords/Search Tags:Adiponectin, Adiponectin knockout mice, Reverse cholesterol transport, ATP Binding Casete TransporterA1(ABCA1), Atherosclerosis
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