| ObjectiveAtherosclerosis(AS) is a kind of arterial disease, mainly involving large, medium artery, which is the basic disease of the arterial intima lipid accumulation, intimal fibroid, causing the formation of plaque hardens wall, stenosis and then cause a series of secondary disease. AS is the pathologic basis of a variety of cardiovascular and cerebrovascular disease. Recent studies have found, AS continuously detected in inflammatory cells and inflammatory mediators, both in AS start, progress of the disease or thrombotic complications formation, inflammation always played a central role. Chinese medicine believes that AS is closely related with sputum, phlegm is the body’s organs and blood loss, fluid transport and disorders pathological product, is a crime against wide risk factors. Therefore, to explore the occurrence of atherosclerosis development mechanism to prevent and treat cardiovascular diseases top priority. At the same time, by atherosclerosis rabbits models fed Ditan Decoction, AS Rabbits histopathological examination of changes in cellular, molecular biological level to study the effects Ditan Decoction on AS rabbit in inflammatory cytokines.Methods48 healthy male New Zealand white rabbits were randomly divided into blank group, atherosclerosis model group, the groups of low、medium and high dose of Ditan Decoction and atorvastatin group, each group of animals eight only. Blank group fed with normal diet; the rest of the group fed with high fat diet. After 8 weeks, randomly selected AS model rabbits 2, after anesthesia, carotid artery blood taken, check blood lipids, suggesting that lipid increased significantly; HE prepared sheet after separation aorta were seen clearly plaque in the vessel wall. It showed AS model be built successfully. AS model group, saline 10 ml / kg for 4 weeks, fed a high-fat diet during continued; Ditan Decoction high dose group were given the high concentration of Chinese herbal medicine(0.738 g / ml) orally, Ditan decoction moderate dose group were given moderate concentrations of Chinese herbal medicine(0.492 g / ml) orally, Ditan decoction low dose group were given low concentration of Chinese herbal medicine(0.266 g / ml) and orally atorvastatin calcium 3mg /(kg.d), each group according to 10 ml / kg once a day orally on time Daily 14:00 stomach 1 times, for 4 weeks during fed a high-fat diet continues. After 12 weeks the rabbits could not eat diet but water 12 h, carotid artery blood 4 m L was drawn the next morning, by automatic biochemical analyzer serum the content of Tc, TG, LDL-c, HDL-c, SOD and MDA; after ELISA assay serum TNF-α, IL-6, ICAM-1, VCAM-1, the application of sodium pentobarbital(25 mg / kg) intravenous anesthesia New Zealand white rabbits, quickly separated from the heart into the aorta between the iliac artery bifurcation, the fat tissue around the arteries cleaned and removed, and took the diameter of 3 mm in the aortic arch tissue for HE staining and Western blot was used for aortic NF-κB, E-selectin protein expression, detected TNF-α、 IL-6m RNA expression and by immunohistochemical assayed ICAM-1 by fluorescence quantitative PCR, VCAM-1 expression was detected.Results1 Effect of Ditan decoction on atherosclerosis of the rabbit model of serum Tc, TG, LDL-c: Ditan decoction can reduce AS rabbit serum Tc, TG, HDL-c, LDL-c, and a dose-dependent, compared with model group, with significant difference(P <0.01 or P <0.05).2 Effect of Ditan decoction on atherosclerosis of the rabbit model of serum SOD, MDA: Ditan decoction can improve AS rabbit SOD levels, lower MDA levels in a dose-dependent, compared with model group, with significant difference(P < 0.01 or P <0.05).3 Effect of Ditan decoction on atherosclerosis of the rabbit model of serum TNF-α, IL-6, ICAM-1, VCAM-1: Ditan decoction can reduce the rabbit aorta serum TNF-α, IL-6, ICAM-1, VCAM-1 expression in a dose-dependent, compared with model group, with significant difference(P <0.01 or P <0.05).4 Effect of Ditan decoction on atherosclerosis rabbit model of aortic NF-κB and E-selectin protein expression : Ditan decoction can decrease the expression of NF-κB on the AS rabbit aorta and E-selectin protein in a dose-dependent,compared with model group, with significant difference(P <0.01 or P <0.05).5 Effect of Ditan decoction on atherosclerotic rabbit aorta model of TNF-α, IL-6 m RNA expression : Ditan decoction can reduce the rabbit aorta TNF-α, IL-6 m RNA expression in a dose-dependent compared with model group, with significant difference(P <0.01 or P <0.05).6 Effect of Ditan decoction on atherosclerosis rabbit model of aortic ICAM-1, VCAM-1: Ditan decoction can reduce the rabbit aorta ICAM-1, VCAM-1 of expression in a dose-dependent,compared with model group, with significant difference( P <0.01 or P <0.05).7 Effect of Ditan decoction on atherosclerosis rabbit model of arterial histopathological changes: Blank group wall were observed thickness in the aorta, intimal smooth and complete, without AS plaque formation; AS model group, the intimal layer flat or uplift, subintimal seen a lot of foam cell aggregation and extracellular lipid deposition; Ditan decoction low dose group, subendocardial accumulation of foam cells and extracellular lipid deposition began to decrease; Ditan decoction moderate dose group, subintimal foam cell aggregation and deposition of extracellular lipid reduction were more obvious; Ditan decoction high dose group, subendocardial accumulation of foam cells and extracellular lipid deposits decreased; atorvastatin calcium group, subendocardial foam cell aggregation and cell outer lipid improving effect were same as the Ditan decoction high dose group.Conclusion1.In this experiment, the model of atherosclerosis was successfully made by using high fat diet. The theory of traditional Chinese medicine believed that "phlegm" is closely related to hyperlipidemia. Therefore, the conclusion is that atherosclerosis is closely related to the "phlegm" of TCM.2.In this experiment, it was tested that there was a high level of serum lipids and increased expression of inflammatory cytokines in atherosclerotic rabbits. It is concluded that the occurrence and development of atherosclerosis is closely related to the abnormal blood lipid and inflammatory reaction. 3.Ditan decoction has a role in regulating lipid metabolism, and can improve the ability of anti-oxidative stress, with lower-induced atherosclerosis role of inflammatory cytokines. |
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