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Expression Of Inflammation Related Genes In ApoE Deficient Mice

Posted on:2009-12-16Degree:MasterType:Thesis
Country:ChinaCandidate:W JingFull Text:PDF
GTID:2144360242494575Subject:Cell biology
Abstract/Summary:PDF Full Text Request
Cardiovascular and cerebrovascular diseases are serious threat to human health. The mortality rate caused by which is rising and the pathologic basis is atherosclerosis (AS). There are multiple theories on AS, but chronic inflammatory reaction theory and disordered lipid metabolism theory is agreed with. The two in organism influence mutually, participate in and promote the development of AS.Apolipoprotein E deficient mice (apoE-/-) is the commonly used model for AS research. The mice can generate AS spontaneously in ordinary diet. And with the age of mice increasing, the pathological changes more seriously. The pathological character is same to it of human. So, the generate mechanism of this disease may be similar to human's. The apoE-/- mice is a superordinary model.However, the paper about detecting systematically the inflammation related genes'expression and the coaction at the earlier period of AS are seldom. So the experiment used the apoE-/- mice as a model to detect the expression of inflammation related genes in aorta, liver and spleen at the earlier period of AS. The purpose is to reveal the danger factors playing key role and the mechanism in AS, to prepare for the further study of molecular biology on AS.The experiment used apoE-/- mice and wild mice which had the same genetic background (C57BL/6J). An RT-PCR assay had been used to analyze expression patterns of inflammation related genes in aorta from 1 to 3-month and liver, spleen from 14-day to 3-month old of atherosclerotic model, apoE-/- mice in normal chow diet. The level of plasma lipids was also analyzed. Combined with the pathomorphological characteristics of the aortic root, we studied on the sequential expression characteristics of AS related genes in the early stages of the AS.ApoE-/- mice compared with WT mice, the expression of genes in the aorta were detected using RT-PCR. The expressions of the VCAM-1, IκB-α, TGF-βand SOD1 in 1-month old of the apoE-/- mice were prominently up-regulated; while the expressions of the PDGF-αand CD36 were significantly up-regulated in 2-month old; the mRNA levels of the TNF-αand MMP2 in 3-month old mice were also prominently up-regulated, and the IL-1βwas significantly up-regulated from 1 to 3-month old, but the Albumin was down-regulated significantly from 1 to 2-month old mice. The genes detected in the liver, the mRNA levels of the CRP and JAK1 were significantly up-regulated at 3-month old of the apoE-/- mice. The genes detected in the spleen, the mRNA levels of the GM-CSF and SOD1 were significantly up-regulated at 2-month old of the apoE-/- mice.The mRNA levels of the NF-κB and other genes detected in liver had no significant changes at different ages in the aorta, liver and spleen in the two types of mice.ApoE-/- mice compared with WT mice, the genes detected in the aorta using Real-time RT-PCR, the expressions of the TNF-α, ICAM-1, VCAM-1 and GM-CSF in 1-month old of the apoE-/- mice were prominently up-regulated; while the mRNA levels of IL-1β, TNF-α, MCP1, ICAM-1, VCAM-1 and GM-CSF were prominently up-regulated in 1-month old of the apoE-/- mice; but the NF-κB and IκB-αhad no significant changes at different ages.Serum TC, LDL-C and HDL-C levels in different ages of apoE-/- mice were significantly higher than those of WT mice. TG level was significantly up-regulated from 1 month old mice, and was rising with the age increasing.It appeared lipid deposition in the intima of aortic root in 1-month old apoE-/- mice. With the increasing of age, the lesions became more serious.It appeared fat drops in the cells of liver of 1-month old apoE-/- mice. With the increasing of age, the drops became bigger in appearance and larger in numer.The results implied that the sequential and differential expression of genes related to AS formed a complex regulatory network which NF-κB is the core, and the genes may interact with each other and play important roles in the early stages of AS of apoE-/- mice.
Keywords/Search Tags:apoE deficient mice, inflammation related genes, aorta, liver, spleen
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