Shugan Fat Particles To Delay Or Regression Of Atherosclerotic Plaques Experimental Study On Mechanism

Background:Cardiovascular disease resulting from atherosclerosis (AS) is the leading cause resulting in higher morbidity, modatily and sudden death. More than 300 patients hourly died from cardiocerebrovascular disease by epidemiological data in china. Most important is the average trending to be younger which would focus the primary prevention on emergent frontiers.The basic pathological characteristic is proliferation and migration of vascular smooth muscle cells(VSMCs) which correlated with over-degeneration of extracellular matrix(ECM). The main stimulus for proliferation and migration of VSMCs is oxidized low-density pipoprotein(Ox-LDL) by activating proteinase leading to multiple pathophysiological pathways. However, the role of CD40/CD40L by signal transmitting way in change of activity of MMPs which was the main mechanism contributing to further endothelial injury and SMCs proliferation and/or migration still remains unclear although the effect of CD40/CD40L in immuno-regulation of progression and stability of atherolsclerotic plaques has been identified. Objectives: To determine the pathophysiological role of hyperlipidaemia in development and progression of AS in New Zealand rabbit model and compare our own traditional Chinese medicine ofrabbit model and compare our own traditional Chinese medicine of SHU-GAN-QING-ZHI granule(SGQZs) with commonly used simvova statin. Methods: Five steps were induced in the present study. Firstly, animal model with hyper lipedaemia was established by high-fat diet; secondly,the effect of SGQZs on vascular endothelial functions was determined by biochemistry,IRAA and detection of vascular active cytokines; thirdly, activity of Ox-LDL, MMP-2,MMP~9 and CD40/CD40L was analysed by immuohistochemistry and RT-PCR; fourthly, ultra-structure of carotid artery was determined by optical and scaning electron microscope; finally, the regression and/or progression of plaques on the surface of endothelium in carotid artery was calculated by colour Doppler sonography.Results: Animal model demonstrated the successful hyperlipedaemia spectrum with typical increased TG, LDL-C, Ox-LDL and decreased HDL-C. The abnormal activity in MMp and CD40/CD40L was reversed by SGZGs complicated with reduction of TC,LDL-C, Ox-LDL and increase of HDL.The net medical effect of SGZGs with high dose was the regression of plaques, and no severe side effects ,including muscle disease(rhabdomyolysis)and hepatic impairment,were detected in high dose SGQZs group compared to simova statin.Conclusions: Serial effects of SGQZs on regression and stablizztion of palque by decreasing plasma level of cholesterol directly, and inhibiting SMCs proliferation and mogration by anti-inflammatory pathways, were identified in the present study. The results demonstrated SGQZs was safe and feasible in traetmen of hyperlipedaemia.