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The Prevention Of Curcumin To Cardiovascular Hypertrophy

Posted on:2004-05-19Degree:MasterType:Thesis
Country:ChinaCandidate:M L YeFull Text:PDF
GTID:2144360092495594Subject:Cardiovascular Pharmacology
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BackgroundHypertension and its relating diseases are the main diseases threatening to human beings. And its incidence rate is on the top of the non-infect diseases. Recent studies have demonstrated that cardiovascular remodeling , especially vascular remodeling play a key role in the formation and development of cardiovascular hypertrophy in hypertension. And cardiovascular remodeling correlates to the disfunction of multiple signaling pathways. Some stimulators, such as mechanical strech, neuro-endocrine factors, contribute to a series of abnormal expression of genes and increased synthesis of proteins by several key players including protein kinase C (PKC), G-proteins, as well as mitogen-activated protein kinase(MAPK), which have been implicated in the pathways. Nowadays, the studies of extracellular matrix which is involved in the regulation of cardiovascular structures have gradually been focused on. Collagen, as one of most important ingredients, and its accumulation associated with cardiovascular remodeling by at least three parts which are the increased synthesis, the decreased degradation and the improved connection with adhersion molecules. Matrix proteins are degraded by a family of metalloproteinase(MMPs), esp MMP2 in cardiovascular system which can degrade collagen or fibronectin. The process of degradation of ECM proteins is due to the activity of MMPs, and the unequilibrium of synthesis and degradation is one major reason of cardiovascular remodeling. The effect of ECM on cellular function and remodeling of ECM is mainly implicated in integrin and focal adhersion kinase(FAK) pathway. Therefore, efforts should be taken in the inhibition of ECM proteins, reversion the remodeling of heart and vessles and modulation blood pressure indirectly, which will lead to discover or invent a new drug for antihypertension.Curcumin is a major component of turmeric. Curcumin exhibits antioxidant and anti-inflammatory activity, inhibits cancer growth and decrese the synthesis ofcollagen in hepar as well as inhibit MMP activity of dermis. One report showed that Curcumin can be mediated through inhibition of protein tyrosine kinase activity, which is an inhibitor of c-Jun N-terminalkinase JNK/AP-1. These results contribute to the application of anti-carcinoma, anti-atherosclerosis, as well as regeneration of liver injury and wound healing. However, the impact of Curcumin on cardiovascular remodeling which links to synthesis of collagen, the activity of MMPs and expression of integrin is unknown.Objective1 .To study the effect of curcumin on the extracellular matrix in cardiac overloaded rats is to undergo the mechanism of this drug on cardiovascular hypertrophy.2.To study the effect of curcumin on the extracellular matrix of cultured aorta smooth muscle cells induced by angiotensin II is to undergo the mechanism of this drug on vascular hypertrophy.Methods and results1 .Effect of Curcumin on cardiovascular hypertrophyCardiac overloaded model was made by partial click of the abdominal aorta in Sprague-Dawley rats. Curcumin , 100ing-kg-1-d-1 for 3 weeks, was given by po 1 week after the click operation. The ratio of heart wet weight to body weight and left heart weight to body weight , aorta wet weight to body weight were calculated ; Morphosis changes of heart and aorta were evaluated by HE stain; Cells derived from rat vascular smooth muscle were cultured and were given 1, 5 , 10, 50, 100 mol-L -1 Curcumin after 30 min when cells were stimulated by 0.1 mol-L-1 angiotensin II. [ H]-TdR method can be applied to evaluate the synthesis of DNA.Results have been showed that in cardiac overloaded rats, the ratio of heart wet weight to body weight and left heart weight to body weight, aorta wet weight to body weight were increased. Compared with the cardiac overloaded rats without any drugs, The ratio of heart wet weight to body weight and left heart weight to body weight, aorta wet weight to body weight were reversed in curcumin-treated rats,but cannot to normal; From cellular level, cell...
Keywords/Search Tags:Curcumin, cardiovascular hypertrophy, remodeling, cardiac overloaded, extracellular matrix(ECM), signal transduction, collagen, matrix metallproteinase (MMP), integrin, focal adhesion kinase(FAK), Tetrandrine, Telmisartan.
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