The Research Of Effect And Mechanism Of Carvedilol In The Formation Of Rat Atherosclerosis

Atherosclerosis and cardiovascular and cerebrovascular diseases due to endanger human health is the major diseases as a result of the important causes of human deaths on the pathogenesis and prevention of a large number of studies made possible mechanism: inflammation injury response theory, fat Invasion theory, platelet aggregation and thrombus formation theory and the theory of smooth muscle cells, such as cloning. It has recently been proposed atherosclerosis is an inflammatory and immune response [60-62] is injury (pro-inflammatory and immune damage and oxidation) and the reconstruction of the (anti-inflammatory and immune modulation and antioxidant) mechanism, the balance between disorders, including T and B lymphocytes, and other effects of antibody cells in atherosclerosis progress in an important role. 15-LO is a non-ferrous heme oxygenase enzyme, can be free of polyunsaturated fatty acids, the product of 15–eicosacarbon hydroxy acid can increase endothelial cells through the ICAM-1 expression to promote the adhesion of monocytes; 15-LO activity expression can be increased or accelerated atherosclerosis early in the occurrence, and inhibited 15-L0 its product activity can significantly retard atherosclerosis of the occurrence and development, and therefore considered to be close Atherosclerosis related. Many studies found that carvedilol is a new non-selective adrenergic receptor blockers, bothα1 receptorβreceptor and block the dual role, and has antioxidant and antiproliferation role Oxygen free radicals can inhibit vascular endothelial cells and smooth muscle cell damage, widely used in heart failure, hypertension, coronary heart disease and other diseases treatment. It has recently been proposed carvedilol has anti-atherosclerosis, is more specific mechanisms around its antioxidant, and whether there are anti-inflammatory effect of carvedilol characteristics, the present study relatively rare, this experiment has done on this studied and discussed by atherosclerosis possible mechanism.The experimental rats in the establishment of atherosclerosis model on the basis of carvedilol by giving a drug intervention by immunohistochemical methods in the aortic wall 15-LO expression and serum TNF-αand the level of SOD, to discuss the effect of carvedilol on atherosclerosis in the impact and mechanisms.Experimental Methods: 30 healthy male Wistar rats (220-250 g body weight) were randomly divided into the following three groups: 1. the normal control group(10); 2. arteriosclerosis (10); 3. carvedilol Luo (10). Normal control group of normal diet; more than two per million rats given Vitamin D330u/kg bw right leg after intramuscular injection to feed the basis of adding 2% cholesterol, 0.5% sodium cholate, 0.2% Propylthiouracil - Vitamin D3 powder (1.25×10~6u/kg feed), 3% lard and other feed. Carvedilol group at the same time given carvedilol 20 mg / kg body weight, once a day gavage. Experiment at the start of the experiment were measured every three weeks weight, feeding nine weeks after the 24-hour fasting blood and death, blood lipid automatic biochemical analyzer detected using spectrophoto- metry and enzyme-linked immunosorbent assay (ELISA) respectively detection of dismutase (SOD) and tumor necrosis factor-α(TNF-α) level, the aortic arch, about 1 cm artery organizations collecting the 1 cm with a fixed 4% formaldehyde solution, HE staining and immunohistochemical analysis.The results: 1,lipids: Compared with normal control group, arteriosclerosis carvedilol group and the group of TC,TG,LDL-C was significantly increased (P<0.01), and HDL-C was significantly lower (P<0.01), and that the two groups had no significant differences in blood lipids. 2,SOD: The results showed that atherosclerosis SOD group was significantly lower than the other two groups (P<0.001), carvedilol group and the normal control group showed no significant difference (P>0.05). 3,TNF-α: compared to the normal control group, arteriosclerosis carvedilol group and the group of TNF-αsignificantly increased (P<0.01), and between the two groups also have significant difference (P<0.001). 4,HE pathology staining: atherosclerotic vascular wall are typical group of atherosclerosis and intimal thickening, vascular lumen intima to highlight, that is full of foam cells, and that inflammatory endometrial hyperplasia of the smooth muscle cells and cells, the destruction of elastic plate, in the medial smooth muscle cells proliferation; carvedilol group in the membrane and vascular endothelium were not significantly hyperplasia, a small number of endothelial visible scattered in the lipid deposition and formation of foam cells and inflammatory cell infiltration. 5,and semi-quantitative immunohistochemical analysis showed that: 15-lipoxygenase (15-LO), the expression of atherosclerosis was significantly higher than the other two groups (P<0.001) in the carvedilol group has also increased, but normal group there was no significant difference.Conclusion: 1. carvedilol has great anti-atherosclerosis in the role of the mechanism of inhibition and 15-LO and the antioxidant and anti-inflammatory effects.2. carvedilol significantly inhibited the activity of TNF-α, thereby inhibiting the atherosclerotic inflammatory reaction.