Mechanism Of Atherosclerosis Caused By Homocysteic Acid And Interventing Effect Of Guanxinkang(Complex Prescription)

Objective: By setting up arabbit HHcy model, to observe the Hcy density of bloodplasma, change of blood fat and the expression of MCP-1, VCAM-1, Bcl-2, MMP-2 inendotheliocyte of aorta, analyze their relationship with formation of AS, and thenanalyze the antagonistic effect of Guanxinkang(traditional Chinese medicine) for thepathological changes of HHcy and AS induced by homomethionin diet, so as to provideexperimental numerical data for the effectiveness of traditional Chinese medicineto interfere in functional impairment of endothelial tissue and athero- pathologicalchanges in earlier period.Method: By setting up a rabbit HHcy and AS model induced by homomethionin diet,to observe the influence of Guanxinkang(traditional Chinese medicine) on the levelof blood fat, tHcy in blood plasma and the expression of MCP-1,VCAM-1, Bcl-2,MMP-2in endotheliocyte of aorta in model rabbit with HHcy. 30 masculine Zelanian albinorabbit have been selected for the experiment. The albino rabbit were divided intothree groups randomly, each of which was t0. The three groups include: 1) normalcontrol group(control group): fed by elementary animal feeds(100 g/d); 2) homocysteicacid model group(model group): fed by homomethionin animal feeds(adding 1% methionineinto elementary animal feeds); 3) Guanxinkang intervention group(interventiongroup): fed by homomethionin animal feeds(100 g/d) and Guanxinkang powder 1.45g/(kg·d)(as 10 times of dosage of human being). Guanxinkang powder used byintervention group are diluted by distilled water then intragastric administrationby 2 ml/kg. Identical volume distilled water are fed to control group and model group.Each rabbit is fed in different cage; water is fed freely and all are fed for 8 weeks.Each group is taken suctionarterial blood for 4ml on an empty stomach in the 0, 4th,8th week respectively, then to test the serum total cholesterol (TC),triglycerideTG),low density lipoprotein cholesterol (LDL-C)and high-density lipoproteincholesterol (HDL-C) by enzymic method using automatic biochemistry analyzer, and totest the contents of homocysteic acid in blood plasma by cyclophorase method. At theend of the 8th week, blood is taken and the animal is put to death, and split ascendingaorta to abdominal aorta. Then to take vascular tissue 1 cm in arcus aortae, firstlywashed by normal saline, then fix it for 2～4 hours in 10% formaldehyde and keepedfreezing by liquid nitrogen for further test. To test the expression of aortaMCP-1mRNA by RT-PCR method; and test albumen expression of VCAM-1, Bcl-2, MMP-2and HE dyeing by immunohistochemistry. To observe the pathological change of aorta. Results: The tHey and blood fat level in blood plasma and expression of MCP-1mRNAof aorta on model group is obviously higher than that of control group (P＜0.05);the result of immunohistochemistry shows that the expression of VCAM-1 and MMP-2enhanced, Bcl-2 is lower; aorta slice shows endarterium discontinuation, strippingpartly, smooth muscle cell arrange puffly and chaotic, infiltration of lipoid ofdifferent degree are observed in aorta wall, pathological changes suffusion, morexanthoma cell, plaque protrude lumens. The they and blood fat level in blood plasmaand expression of MCP-lmRNA, VCAM-1, MMP-2 of aorta on intervention group aremuch lower than that of model group (P＜0.05); Bcl-2 of intervention group isstrengthened, and the pathomorphology and immunohistochemistry of aorta showpathological changes are slighter than model group.Conclusion: 1) HHcy may increase the level of homocysteic acid in the blood andresults in the formulation of AS plaque and higher expression of MCP-1mRNA,VCAM-1, MMP-2 but lower expression of Bcl-2. 2) Guanxinkang may decrease the the levelof homocysteic acid in the blood, improve the metabolic disturbance of lipoids,alleviate the hyperplasy of endangium, antagonize various factor cause AS and hasevident role in anti-AS.