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Effect of Losartan on Inflammatory Factors in Atherosclerotic Rabbits

Author: YuLiNa
Tutor: XuYanMin
School: Tianjin Medical University
Course: Internal Medicine
Keywords: atherosclerosis inflammation angiotensin Ⅱ losartan C-reactive proteininterleukin-6
CLC: R543.5
Type: Master's thesis
Year: 2010
Downloads: 6
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Abstract


Objective:Coronary heart disease is one of common disease nowadays which threaten peoples health. Atherosclerosis is the basic pathological mechanism of cardiovascular disease and cerebrovascular disease. Since last century, it has attracted many researchers attention from all over the world. In recent years, researchers have detected the inflammatory cells and the inflammation factors in the atherosclerotic plaque, atherosclerosis no longer be considered a pure arterial wall lipid deposition disease, but progressive inflammatory disease. Angiotensin Ⅱ could induce the expression of multiple inflammatory factors and promote the proliferation of smooth muscle cells involved in the occurrence and development of AS. Angiotensin-1receptor antagonist by blocking the Angiotensin Ⅱ and Angiotensin-1receptor binding produced by a series of biological activity, inhibit the formation and development of AS. Angiotensin-1receptor antagonist on the role and mechanism of anti-atherosclerosis has become a new hot spot in recent years. In this study, we established the atherosclerosis rabbit model through balloon injury and high-fat raising. We try to observe the expression of Angiotensin Ⅱ and inflammatory factors in the rabbit atherosclerosis model and Angiotensin-1receptor antagonist on the intervention of inflammatory factors, thereby clarify the Angiotensin Ⅱ, inflammatory factors in the occurrence and development of atherosclerosis in the mechanism, so as to diagnosis and treatment of atherosclerosis to provide a new way of thinking.Methods:32New Zealand rabbits were randomly divided into three groups:control group, high-cholesterol group and losartan group. The balloon-injured iliac artery angioplasty was performed in the rabbits of the high-cholesterol group and losartan group which were raised with high-cholesterol food, the sham operation was performed in the control group which were raised with normal diet. Four weeks later, rabbits in each group were conducted a vascular ultrasound testing to determine the formation of atherosclerotic plaque. Thereafter, we added25mg/kg-d losartan to each rabbit s daily food in losartan group. After another eight weeks, all the rabbits were sacrificed, and the iliac arteries were harvested for morphometrical and hybridization analysis. The length of vascular intima and media were measured under microscope, and the ratio of the lengths was calculated. The positive expressive area of C reactive protein was also measured. During the experimental process, the weights of the rabbits were measured regularly. The serum lipids and inflammatory factors were measured in the fourth and the twelfth week respectively. The statistical software SPSS13.0was used for data analysis.Results:①At the end point of experiment,29rabbits were analyzed statistically. The weights of rabbits in three groups rise significantly (P<0.05). But there is no statistical difference between these three groups.②In the fourth week, vascular ultrasound confirms atherosclerosis model has been established successfully in the-high-cholesterol group and losartan group, but the two groups of IMT, lumen diameter, blood flow velocity was no statistical defference.③In the fourth and the twelfth week, the serum lipids of rabbits in high-cholesterol group and losartan group rise significantly in comparison with control group (P<0.05), but there is no statistical difference between them.④Serum CRP, IL-6are higher in high-cholesterol group and losartan group, compared to control group. They are almost the same in losartan group and high-cholesterol group in the fourth week, and they become lower in the twelfth week in losartan group (P<0.05). Furthermore, serum CRP, IL-6are lower in the twelfth week than the fourth week in losartan group, and compared with the fourth week, there is no significant difference at the twelfth week in high-cholesterol group and losartan group.⑤Angiotensin Ⅱare higher in high-cholesterol group and losartan group, compared to control group (P<0.05). But there is no statistical difference between them.⑥The ratio of intima-media length are higher in high-cholesterol group and losartan group, compared to control group (P<0.05), and the ratio in losartan group is lower than high-cholesterol group.⑦There is low level expression of CRP in control group. However, the level of CRP is higher in the high-cholesterol group and losartan group, and the expression of CRP is evidently decreased in losartan group compared to high-cholesterol group.Conclusion:①Feeding hyper cholesterol diet for4weeks followed by iliac artery balloon denudation can create rabbit AS animal model successfully. The histological characters have favorable comparability with human AS lesions.②There is high level expression of serum CRP, IL-6in rabbit model of atherosclerosis, Angiotensin Ⅱ levels were also significantly increased. It indicates that AS has a relationship with inflammatory factors, and the inflammatory response may be induced by Angiotensin Ⅱ.③Losartan can ameliorate the experiment atherosclerosis rabbits’ iliac artery. Thus it can prevent the development of atherosclerosis, and this function is independent of the function of reducing the blood fat.④Losartan can reduce serum CRP, IL-6levels, which has anti-inflammatory effects, but the role of the mechanism is not by lowering the angiotensin II achieved.⑤The CRP level increases significantly in the atherosclerosis rabbits, and losartan can significantly decrease the level of serum and plaque CRP, which may be one of the mechanisms of losartan s anti-atherosclerosis.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Vascular disease > Artery disease
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