| BACKGROUNDAtherosclerosis is one of most serious diseases which result in cardiovascular and cerebrovascular disease. The morbidity and mortality of AS, CAD and cerebral paralysis rise year by year, furthermore which go by low agetendency and progressively develop and lead to brain dsyfuction function, even severe cardiovascular incidents, dysprognosis, low quality of life. How to prevent and cure the development of cardiovascular disease and cerebrovascular disease is main duty to medical worker. The concomitance base of pathology of cardiovascular disease and cerebrovascular disease is AS. So the key point of prevention and cure of the cardiovascular disease and cerebrovascular disease is to prevent the AS.Long term high fat diet and metabolic disorder of lipid corelate with many kinds of cardiovascular diseases. Hyperlipemia and the subsequent formation of atherosclerosis is one of the most risk factors for ischemic heart disease. The mark of cardiovascular disease is endothelium disfunction. Oxidative stress has been involved in the early steps of atherosclerosis. An increasing body of evidence suggests that oxidant stress is involved in the pathogenesis of many cardiovascular diseases, including hypercholesterolemia, atherosclerosis, hypertension, heart failure and diabetes,and endothelium apoptosis involved in Oxidative stress. The end product of lipid peroxidation was MDA in vivo,which indicated the velocity and intensity of peroxidize. Antioxidant enzymes, especially the three isoforms of superoxide dismutase (SOD), modulate basal levels of superoxide and protect against vasomotor dysfunction. A common gene variant of extracellular SOD (ecSOD) is associated with increased risk of ischemic heart disease. Myeloperoxidase (MPO), a heme protein abundantly expressed in polymorphonuclear neutrophils, which can reduce NO result in dysfuction of vasomotion. Reduced vascular nitric oxide (NO) bioavailability is a major contributing factor in the initiation of atherosclerosis.Traditional Chinese drug cure AS in long history.there great progression has been to make in AS, and with tiny toxic side effect, multistrata, mulcomponent and multarget in anti- atherosclerosis. To explore the anti-atherosclerosis effection of Chinese drugs pharmaceutics on atherosclerosis. Thus, we established AS rabbits with high fat diet to research mechanism of Bu Xin Tong Mai Granule in the model and provided support for clinic curing.OBJECTIVETo investigate the effects mechanism of Bu Xin Tong Mai Granule on the level of blood lipid, blood plasma nitric oxide and myeloperoxidase(MPO), malonaldehyde(MDA), superoxide dismutase(SOD) and patho-accumulated points of atheromatosis in atherosclerosis model rabbit, which induce by high fat diet, in order to provide academic foundation on resisting atherosclerosis by bu xin tong mai Granule revolutions per minuteMETHODSThe rabbit model with atherosclerosis induced by high fat diet.40 healthy male rabbits were randomly divided, by random digits table, into 5 groups:control group, model group, low dose (2g/kg·rabbit) Bu Xin Tong Mai group, high dose(8g /kg-rabbit) Bu Xin Tong Mai group, Simvastatin group. The control group fed with common rabbit forage. Simvastatin and Bu Xin Tong Mai Granule were by intragastric administration for 3 months. We got blood 5ml from vein of ear, then set it in standing room temperature for 1 hour, centrifuge for 5 minutes with 3000 rpm, which was wait for detect. We anesthetized through blood vessel injection by 3% Pentobarbital(50 mg/kg), routinely sterilized, unfolding cervical part cutaneous and muscle. The arteria carotis was washed with PBS and stripped adventitia as far as possible, and fixed with Formaldehyde routinely. The vascular tissue was cut into lcm. then set to glass slide to fix with over-strain membrane. 12 weeks after the intervention of Bu Xin Tong Mai Granule, We observed alterations of levels of blood lipid. triglyceride (TG) was measured by CHOD-PAP method, total cholesterol (TC) was detected by CHOD-PAP and low-density lipoprotein cholesterol (LDL-c) and high-density lipoprotein cholesterol (HDL-c) was measured by selectivity precipitation method. The arteria carotis was taken for pathologic analysis with HE stain. Plasma NO was determined by nitric acid reductase.. MPO was determined by anisidine,MDA was determined by thibabituric acid method and also to detect the level of SOD.Statistical method:The data was analyzed by SPSS 13.0 statistic software. Values are presented as means±SD. Comparisons among groups were performed by one way ANOVA analysis. if the variance to be equalized, two sets data were analyzed with LSD test. if the variance to be not equalized, two sets data were analyzed with Tamhane's T2 test. Ap≤0.05 was considered significant.RESULTS1. Blood lipidAfter the rabbits in model group underwent fed high fat diet for 12 weeks, TG,TC and LDL-c of model group were increased (P<0.01, vs control group).HDL-c of model group was decreased (P<0.01, vs control group). TG and TC in Bu Xin Tong Mai Granule and Simvastatin group were significantly different from model group (P<0.05), The levels of TC,TG,LDL-c and HDL-c in low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group were roughly identical to sham group(P=0.147;P=0.862;P=0.285);(P=0.076, P=0.410, P=0.639);(P=0.158, P=0.178, P= 0.440);(P=0.053, P=0.856, P=0.919). LDL-c and HDL-c in low dose bu xin tong mai group had no obvious difference to control group (P=0.158, P=0.053)2. Arteria cervicalis HE staining.Sample from control group showed intact endothelial layer and no smooth muscle proliferation. Endothelial cell sloughing, and smooth muscle proliferation and irregular cell form were observed in model group, and also lipid droplet vacuoles in cytoplasm of the endothelial cells Simvastatin group showed attenuated morphologic changes of endothelial and smooth muscle cell. There is lipid droplet vacuoles in cytoplasm of the endothelial cells and smooth muscle proliferation in low and high bu xin tong mai group.3. Plasm level of NO and MPOAfter fed with high fat diet for 12 weeks, Plasm level of NO in model group was decreased (P<0.001) compared with that in control group. Plasm level of NO in low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group were increased compared with model group (P<0.01), and had no obvious difference to control group (P=0.1228, P=0.0624, P=0.0581). There was no visible disparity among low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group(P=0.7331, P= 0.7076). Plasm level of MPO in model group was decreased (P<0.001) compared with that in control group. Plasm level of NO in low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group were increased compared with model group (P<0.01), and had no obvious difference to control group (P=0.4650, P=0.0606, P=0.4932). There was no visible disparity between high dose bu xin tong mai group and Simvastatin group(P=0.9634). Compared with low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group were increased (P<0.05)4. MDA and SOD of arteria carotisAfter fed with high fat diet for 12 weeks, the level of SOD in model group was decreased (P<0.05) compared with that in control group. The level of SOD in low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group were increased compared with model group (P<0.01 or P<0.05), and had no obvious difference to control group (P=0.477, P=0.163, P=0.115). There was no visible disparity among low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group(P=0.368, P=0.480). The level of MDA in model group was decreased (P<0.001) compared with that in control group. The level of MDA in low dose bu xin tong mai group,high dose bu xin tong mai group and Simvastatin group were increased compared with model group (P<0.01), and had no obvious difference to control group(P=0.304, P=0.187, P=0.054). There was no visible disparity among low dosebu xin tong mai group, high dose bu xin tong mai group and Simvastatin group(P=0.758, P=0.336).CONCLUSIONS1. The result show that TG,TC and LDL-c with feeding high cholesterol diet were significantly increased, and HDL-c was significantly decreased,and arteria carotis endarterium was obviously thickening and with lipidoses inserted to vein wall. We copy succeedly model rabbit with with feeding high cholesterol diet.2. The result show that plasm level of NO and the level of SOD in arteria carotis were decreased obviously.The plasm level of MPO and the level of MDA in arteria carotis were increased obviously in model group.3. Bu xin tong mai Granule can decrease the level of TG,TC, and incease the level of HDL-c.The drug also could improve the pathological change. The drug can elevate the plasm level of NO and the level of SOD in arteria carotis,and can degrade the plasm level of MPO and the level of MDA in arteria carotis4. Bu xin tong mai Granule could anti-atherosclerosis in which might be related to lower level of MPO and MDA and to elevatelevel of NO and SOD. Bu xin tong mai Granule can inhibit process of atherosclerosis in atherosclerosis rabbit, and have similar effect with Simvastatin. |
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