Study On Mechanisms Of Antiatherogenic Effects Of Zhengzhi Pellet In High Cholesterol-fed Rabbits

Background and objective Atherosclerosis is the leading cause of morbidity and mortality in populations. Many factors such as dyslipidosis,endothelial dysfunction and smooth muscle cell proliferation play an important role in atherosclerosis. Numerous studies demonstrate that Chinese herbal medicine can attenuate atherosclerotic lesions by different mechanisms. Our previous results showed that Zhengzhi pellet can attenuate atherosclerosis. But its mechanisms remain unclear. The aim of this study was to investigate the mechanisms of antiatherogenic effects of Zhengzhi pellet.Methods Male New Zealand white rabbits were randomly divided into four groups of 6 each. Rabbits were fed regular chow (control group),chow with 1% cholesterol and 5% fat (model group),chow with 1% cholesterol and 5% fat plus Zhengzhi pellet ( Zhengzhi pellet group ),chow with 1% cholesterol and 5% fat plus vitamin E (VE group). Blood samples were collected at 0,4th,8th for determination concentrations of triglyceride (TG),total cholesterol (TC),low density lipoprotein cholesterol (LDLc),high density lipoprotein cholesterol (HDLc),very low density lipoprotein cholesterol (VLDLc),oxidized low density lipoprotein (oxLDL),nitric oxide(NO) and serum lipoprotein electrophoretagram. At the end of experiment,the animals were sacrificed and the aorta and heart were harvested for measure of extent of aortic atherosclerosis and coronary atherosclerosis.Results1. Rabbits fed with high fat and cholesterol diet had higher levels ofserum TC,TG,LDLc,VLDLc,which paralleled the severity of the atherosclerosis. Rabbits fed with high fat and cholesterol plus Zhengzhi pellet chow had lower serum TC,TG,LDLc,VLDLc concentrations compared with rabbits in model group (P<0.05). But there was no difference in HDLc level between rabbits of Zhengzhi pellet group and model group (P>0.05). Serum lipoprotein electrophoretagram showed a decreased proportions of AL,a LP2,a LP3,a LP4 zone and an increased proportion of int P LP zone in rabbits of model group,Zhengzhi group and VE group. Rabbits of Zhengzhi pellet group had higher proportions of AL,a LP2,a LP3,a LP4 zone and lower proportion of int P LP zone compared with rabbits of model group(P<0.05).2. Rabbits fed with high fat and cholesterol chow had higher level of oxLDL. Rabbits of Zhengzhi pellet group and VE group had lower level of oxLDL compared with rabbits of model group (P<0.05). There was no difference in oxLDL level between rabbits of Zhengzhi pellet group and VE group (P>0.05).3. Rabbits fed with high fat and cholesterol chow had lower level of NO. Rabbits of Zhengzhi pellet group and VE group had higher level of NO compared with rabbits of model group (P<0.05). After 8 weeks,level of NO in rabbits of Zhengzhi pellet group was higher than that of VE group (P< 0.05).4. The reduction of atherosclerotic lesion in rabbits of Zhengzhi pellet group and VE group reached statistical significance compared with rabbits of model group (P<0.05). moreover,the intensity of atherosclerosis in rabbits of Zhengzhi pellet group was lower than that of VE group.Conclusions Zhengzhi pellet and VE can attenuate intensity of atherosclerosis. Effect of Zhengzhi pellet was better than VE. Zhengzhi pellet can decrease levels of TG,TC,LDLc,VLDLc,increase level of HDLc. It can increase proportions of AL,a LP2,a LP3,a LP zone and reduceproportion of int P LP zone. Zhengzhi pellet can reduce level of oxLDL and increase level of NO. it might can inhibit LDL oxidation and inhibit vascular endothelial dysfunction. Effect of Zhengzhi pellet was better than VE. It's might because Zhengzhi pellet can antiatherosclerosis by different mechanisms.