Dissertation > Medicine, health > Chinese Medicine > Of Pharmacy > Pharmacology

Effect of Qidan Liquid on Transforming Growth Factor Beta-1, Vescular Cell Adhesion Molecule-1 and Low Density Lipoprotein Receptor in Arteriosclerotic Rabbits

Author XiaXianMing
Tutor ZhouJunQin;LiZhiHua
School Hebei Medical University
Course Basic Theory of Traditional Chinese Medicine
Keywords Qidan liquid Arteriosclerosis lipid peroxidation serum lipid transforming growth factor beta vescular cell adhesion molecule low density lipoprotein receptor
CLC R285
Type Master's thesis
Year 2004
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Objective: Qidan Liquid is an effective medical prescription for the prevention and the cure of syndromes such as chest stasis and heartache, remarkable effect has been shown after clinical application for more than ten years. Atherosclerosis(AS) is the main pathology roo of ischemic heart disease. Transforming growth factor (TGFβ-1), vescular cell adhesion molecule (VCAM-1) , and low density lipoprotein receptor(LDLR) play important parts in the forming of AS. TGFβ-1 can arrest the proliferation and migration of SMC and endothelial cell,restrict the conjugation of lower density lipoprotein (LDL) to macrophage and foam cell,inhibit macrophage from phaging the residual body of very low density lipoprotein(VLDL) or oxidized residual body of VLDL, thus to exert its protection to AS. Expression of VCAM-1 will be upregulated after the damage of angio-endothelial cell, and the ability of VCAM-1 to adhere leucocytes (majority of which is monocyts) will be augmented. Then monocyt immigrates to infra-endothelium, intapes oxidized low density lipoprotein (oxLDL) and changes it into activated macrophage, finally becomes foam cell full of <WP=8>lipid. LDL wil be decomposed by enzymes in lysosome after its binding to LDLR, and cholesterol ester(CE) will be hydrolyzed into free fatty acid(FFA) by acid lipase. FFA can arrest 3-hydroxy-3-methyglutary-coenzyme A (HMG-CoA) reductase after promoted, that will reduce the intracellular self-synthesis of cholesterol and activate the fatty-acyl- coenzyme A-cholesterol acyltransferase in cytoplasm, the later esterificates FFA into CE and depots it in cytoplasm. This can accelerate the clearance of LDL in plasm. In this research, we created AS rabbits model by feeding high lipid forage, further investigated the actin of lipid metabolic disorder in the onset of AS by detecting VCAM-1 and LDL R in rabbits aorta, TGFβ-1 in both myocardium and arota ,and some lipid-metabolism- related biochemical indexes in serum, also contrasting by nifedipine ,observed the modulating effect of Qidan Liquid (traditional Chinese medicine) on lipid metabolic disorder, to expound its inhibitory and therapeutic mechanism to AS.Method: We divided the twenty-four white New Zealand male rabbits ,which of four months old, into four groups at random, they were normal group,model group,test group and control group. Rabbits of normal group were feeded with common rabbit forage, others were feeded with high lipid forage. The constituent of high lipid forage is : cholesterol(1%) , yolk powder(15%), lard(5%),common rabbit forage(79%). According to body surface area converting formulae between human and rabbit, the rabbits of test group were feeded with Qidan <WP=9>Liquid(3g/ml).A rabbit was feeded 20ml everyday. The rabbits of control group were feeded with nifdepine(40mg everyday to each rabbit). The concentrate of Qidan Liquid and the crush of nifdepine were mixed up with high lipid forage respectively, to manufacture grain forage to feed rabbits. After twelve weeks, all rabbits were taken blood from posterior auricular vein. Splitted blood serum was used to detect biochemical indexes. After bitterning the postanesthesia rabbits’ chests, we took a sprinkle of living thoracic aorta and stabilized it in 4% glutaral, to check the ultrastructural changes by transmissing electron microscope. Then we put the rabbits to death by exsanguinate , took out of hearts and thoracic aorta, treated them with liguid nitrogen and saved in ultra cold storage freezer, to examine the expression of transforming growth factor and low density lipoprotein receptor by reverse transcription polymerase chain reaction. Abdomial aorta were taken from the rabbits and kept in 10% neutralizing formaldehyde stabilization liquid, for the inspection of HE staining and vascular cell adhesion molecule by immunohistochemistry.Results1. Success to creat the atherosclerosis model.2.Changes of lipid metabolism and lipid peroxidation related indexes in serum: Compared with normal group, the serum contents of total cholesterol (TG)、triglycerid

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