The Intervention Study Of The Effect Of Cyclosporin A On The Immunologic Mechanism Of Coronary Heart Disease And Restenosis

Objectives:In this research, through establishing balloon injury iliac artery coronary heart disease(CHD) and restenosis(RS) model, to investigate expression level of the immunoglobulin in serum and the inflammatory factors in the injured iliac artery, and to disscuss the intervention function of cyclosporin A (CSA) on the immunologic mechanism of CHD and RS, for providing a new way of the prevention and treatment of the atherosclerotic disease.Methods:1. Establishing model of rabbit with CHD:forty-eight adult male rabbits were divided into6groups randomly. Normal control group(N), fed with normal food during the whole experiment. Normal food and CSA group(N+CSA):fed with normal food and given CSA10mg/kg/d for4weeks starting from the fourth week. The CHD group(CHD), CHD and CSA group(CHD+CSA), Restenosis group(RS), Rastenosis and CSA group(RS+CSA) fed with1.5%cholesterol diet during the whole experiment. At the fourth week, do the first balloon injury in the four cholesterol diet groups. After the operation, the CHD+CSA group was given CSA10mg/kg/d for4weeks. At the eighth week, the rabbits of N, N+CSA, CHD, CHD+CSA group were killed.2. Eatablishing model of rabbit with RS:At the eighth week, the RS and RS+CSA group were given the second ballon-injury, and the RS+CSA group were add with CSA10mg/kg/d for4weeks. At the twelfth week, the rabbits of RS and RS+CSA group were killed.3. Handing specimens:All rabbits were weighted and exsanguinated at the beginning and ending of the study. The peripheral venous blood were taken to measure routine blood tests, liver function, kidney function, lipids and the immunoglobulins(Igs) including IgE, IgM, IgG. Iliac arteries were taken once the rabbits were killed. Part of the iliac arteries were preserved in formaldehyde, which were used for histological observation. Another part were conserved at the temperature of-80℃, which were used to measure mRNA expressions of the inflammatory factors through reverse transcription and real-time fluorescent quantitative polymerase chain reaction techniques. All data were analyzed through SPSS software(version18.0),and P＜0.05is of statistically significant difference.Results:1. Serum indexes:Before killed, compared with groups of normal food, the cholesterol, triglycerides and alanine aminotransferase levels were higher (p<0.05) in groups of hyperlipidemic diet. At ending of the study, the creatinine levels of the groups with CSA were significantly higher than the beginning.2. Histologic changes:In normal food groups, the vessel wall was bright red, soft texture, and HE staining indicated that the vessel wall is thin. The intima was composed of endothelial cells and internal elastic plate. The VSMCs were in media arranged in rows. In CHD group, the iliac artery the wall is white or pink-white, hard exture, and HE staining indicated that the vessel wall was thick, and the lumen was stenosis. The intima was significantly thickened, and the internal elastic plate was fracture and incomplete,with a large number of VSMCs were visible. In RS group, the color, texture, lumen of the vessel were similar to the CHD group, but more serious. The HE staining indicated that the wall was obvious thick, and the VSMCs hyperplasia, arranging disorderly, and migrated from media to intima crossed the damaged internal elastic plate.3. Igs:Compared with the beginning of the study, there were no statistical differences of changes in IgE, IgM, IgG at the groups of CHD and RS at the ending (P＞0.05). The groups with CSA, levels of Igs had no statistical differences (P＞0.05).4. RT-PCR:Compared with groups of normal food, the expression of MMP-9, VCAM-1, TNF-a tended to increase, and the expression of MMP-1,IL-6showed a decreased trendm, however there were no statistical differences (P＞0.05). After the intervention of CSA, the expression changes of these inflammatory factors were no statistical differences (P＞0.05).Conclision:1. Through balloon injury iliac artery establishing CHD and RS model, the atherosclerosis was stable.2. The Igs levels in CHD and RS were slightly changed, and there were no significant differences after the intervention of CSA.3. The MMP-9, VCAM-1, TNF-a levels in CHD and RS were showing increasing trend compared with the groups of normal food, and the MMP-1,I1-6levels were showing decreasing. There were no significant differences after the intervention of CSA.4. In this study, the benefit of CSA on the immunologic mechanism of CHD and RS could not be confirmed, and the mechanism of CSA on CHD need to be studied intensively.