Study On The Mechanism Of Huazhuo Tongmai Anti-atherosclerosis

Atherosclerosis(AS) isan important pathological basis of cardiovascular and cerebrovascular diseases. Atherosclerosis may cause cerebral infarction and other cardiovascular and cerebrovascular diseases and have become the leading cause of death, whichare seriously threatening the health and lives of human bejings.There is no exact same name, atherosclerosis, in traditional Chinese medicine classics. It ismainly summarized to the syndromes of "xiongbi", "zhenxintong", "stroke", "vertigo", "headache", "dementia", "phlegm", and so on. Generally, the dysfunction of the body and viscera, infirmity of spleen and stomach,and daily greasy diet and impeded qi functionlead to the condition of phlegm turbidity. With the develpment of sputumturbidity in vessles, sputumturbidity changes to phlegm stagnation syndrome. The interrelationship between weakened body resistance and the state of evil domination develops to the pathological status continuously. Therefore, it is considered that the pathogenesis of atherosclerosis is related to phlegm and blood stasis. In clinical practice, treatment for atherosclerosis by removing phlegm has shown remarkableeffects. Huazhuo Tongmai Fang, a prescriptioncreated by Professor Xu Fengqin of Xiyuan Hospital,is usde to treat atherosclerosis and hyperlipidemia by means of resolving phlegm and clearing turbid blood vessels.From the view of modern medicine, the disorder of lipid metabolism is an important cause for the development of atherosclerosis.In the case of long term hyperlipidemia,increased lipoprotein,especially oxidized low density lipoprotein (ox-LDL) cholesterol.causes functional damage to the artery intima.. Increased expression of a variety of inflammatory factors and adherent cells induce mononuclear cells from endothelial cells moved into the intima and become macrophages, which change to foam cells by phagocytosis of lipid,which form the earliest atherosclerotic lesions of fatty streaks.Objective:this study aimed to study the effects of Huazhuo Tongmai Fang on the blood lipid in AS model rabbits, and to explore the possible mechanism of it.Methods:60New Zealand rabbits were randomly divided into5 groupes:black group, model group, simvastatin group and Huazhuo Tongmai Fang groups (low dosage and high dosage). The rabbit model was established by using simple high fat diet, except for the blank control group. Rabbitswere continuously fed with high fat diet for 14weeks in order to induce AS, whileadministrateddrugs for 14weeksconsecutively. Then another 8 weeks were usde as involuting phase. Before and after administration, blood samples were drawn via ear marginal vein for the determination of myeloperoxidase (MPO), total cholesterol (TC), triglyceride (TG), high density lipoprotein (HDL), low density lipoprotein (LDL) and very low density lipoprotein (VLDL), apolipoprotein AI (ApoA-Ⅰ), apolipoprotein B (apoB), alanine aminotransferase (ALT), aspartate aminotransferase (AST), urea nitrogen (BUN), urea (UR), creatinine (Cr). After 22weeks, the thoracic aorta was stained with HE to observe the morphological changes.Results:(1) Lipids testing:After 14 weeks of treatment, compared with the blank group, model group of TC, TG, HDL, LDL, VLDL, ApoA 1, apoB and prior to drug administration increased significantly compared (P< 0.05 or P< 0.01), simvastatin and Huazhuo through pulse size group and model group, TC, LDL, apoB decreased (P < 0.05); after 22 weeks, simvastatin group, Huazhuo Tongmai pulse high dose group and model group was lower than that of TC, LDL, apoB (all P< 0.01) and VLDL decreased (P< 0.05); simvastatin group and Huazhuo Tongmai large pulse dose groups without significant difference.(2) MPO:Afterl4weeks, MPO levels in the plasma of rabbits in the model group and blank control group significantly increased (p<0.01). Compared with model group, MPO levels of rabbits in the simvastatin groups decreased significantly (p<0.01), Huazhuo tongmai Fang groups of high dosage and low dosage decreased(p<0.05).There was difference between the western medicine-treated group and Huazhuo tongmai Fang groups of high dosage and low dosage (p<0.05).(3) HE stainting of rabbit thoracic aorta(×40):In model group, the aortic intima was significantly thickened while a large number of foam cells were visible; smooth muscle cells is in disorder; In the statin-treated group,there was no obvious thickening in the intima and a small amount of smooth muscle cells proliferation:cell arrangement is regular; the structure of each layer is clear. The degree of pathological changes was significantly reduced compared with the model group. In the Huazho Tongmai Fang group, endometrial is less smoothy, with a small amount of endometrial uplifted; blood vessel endothelial cells were integrity, and the structure of each layer is clear. The degree of pathological changes in Huazho Tongmai Fang group was significantly reduced compared with the model group. The results showed that the AS rabbit model was successfully established, and the high dosage group of Huazhuo Tongmai Fang had a certain intervention effect on atherosclerosis of rabbits.Conclusion:(1) High dosage of Huazhuo Tongmai Fang can inhibit the formation of AS aortic plaque in rabbit and reduce the endothelial lipid deposition. There was no significnt difference between the effects of simvastatin and Huazhuo Tongmai Fang.(2) The size of two doses of Huazhuo Tongmai are able to reduce the levels of MPO in rabbit plasma, which may strengthen the anti-inflammatory function of HDL, which may be one of the mechanisms Huazhuo Tongmai anti-AS.(3) High dosage of Huazhuo Tongmai Fang canreduce the levels of TC、LDL、 VLDL、ApoBin rabbit plasma,suggesting that regulate lipid metabolism may be one of the mechanisms Huazhuo Tongmai anti-AS.There was no statisticaldifference between the effects of simvastatin and the high dosage of Huazhuo Tongmai Fang.