Effects And Mechanism Of Danlou Tablets On Lipid Metabolism And Progression Of Atherosclerosis

Objective: With the improvement of human living standard, accelerating workrhythm of life and social aging intensifies, Cardiovascular and cerebrovascular disease ispathologic based on atherosclerosis (AS). There is an upward trend in incidence in ourcountry, and to youg development. Elderly people is often with various chronic diseasessuch as hypertension、coronary heart disease、diabetes and stroke，and associated with highblood pressure, high cholesterol、high blood glucose、plasma high coagulation state and aseries of pathophysiological changes，also need to take more than10kinds of drugs fortreatment at the same time. From the perspective of traditional Chinese medicine, theabove a series of pathophysiological basis can be classified as phlegm-stasis syndrome,which has the characteristics of easy to gather and feasible, and is easy to reverse thedisease stage. We adopted the method of Removing Both Phlegm and Blood Stasis andmulti-pronged thought from traditional Chinese medicine. Some clinical research found,coronary heart disease patients to treatment; the results showed that4weeks westernmedicine standardized treatment with Removing Both Phlegm and Blood Stasisrepresentative drug group improve the aspects of inflammatory markers and plaque tissuefactor obviously superior to western medicine standardized treatment with placebo groups.But at present the specific efficacy of removing both phlegm and blood stasis didn’tresearch clearly, more have not been agreed with the western medicine. Based on the aboveunderstanding, we choose the Danlou tablet which is the only SFDA approvedrepresentative of removing both phlegm and blood stasis，through acute hyperlipidemia ratmodel and chronic hyperlipidemia and AS rabbits model respectively to explore thespecific curative effect and mechanism of cure phlegm first，a part of removing bothphlegm and blood stasis，as well as the size of atherosclerotic lesions in vascular system.For development of Chinese medicine treatment and to overcome the chroniccardiovascular and cerebrovascular disease, we provide important theoretical basis.Methods:1.The effect of Danlou tablets on the regulation of serum lipid on acutehyperlipidemia rats: To prepare acute hyperlipidemia rat model by tail intravenous injection Triton-WR1339, according to the different doses intervention group rats, including threedoses Danlou intervention (2.9g/kg、5.8g/kg and8.8g/kg, n=8) and rosuvastatinintervention (1mg/kg, n=8), carry out blood testing in the different time points after animalmodel building, to detect serum TC and TG level changes.2. The long-term effect of Danlou tablets on regulation of serum lipid and itsantioxidant effect in hyperlipidemia rabbit: In different interventions stage of hyperlipemiarabbit model (blank control、model control、Danlou group2g/kg and atorvastatin group1mg/kg, n=11), every4weeks detected the levels of blood lipid and lipoprotein oxidationdegree, dynamic evaluation of lipid regulation in serum TC, TG, LDL–C, HDL–C andoxidation of LDL levels.3. The impact of Danlou tablets on atherosclerotic lesions in hyperlipidemia rabbitmodel: by12weeks of high-fat feeding and preparation of carotid artery adventitial injuryrabbit AS model, in different intervention group, after intervening20weeks, and to takedyeing immunohistochemical analysis in mold parts of the carotid artery and aortic arch.4. Danlou tablets regulate liver lipid metabolism and the plaques MDA content inhyperlipemia rabbit: end point detection of each animal liver lipid content, expression oflipid metabolism related enzyme, expression of intestine bile acid transporter, expressionof oxidized lipoprotein receptor and the change of MDA content within plaques.5. Statistical approach: The data were expressed as mean±standard deviation amonggroups, using SPSS20.0statistical software analysis, P<0.05was considered statisticallysignificant. To compare multiple samples mean, we use single factor analysis of variance,and multiple double compared with q mean test, about heterogeneity of variance date, weuse nonparametric test.Results:1. The effect of Danlou tablets on the regulation of serum lipid on acutehyperlipidemia rats: Compared with model control group, single high dose Danlou tablet(8.8g/kg)group can obviously inhibit acute elevated serum TC and TG, brought by theintravenous Triton-WR1339(P<0.05), and the TC in each time point was lower one timethan rosuvastatin (1mg/kg) group(P<0.05);7days Continuous dosing experiments foundthat middle-dose Danlou tablet (5.8g/kg) group, compared with model control group, can still play a role of descending TC TG, while the statin group only have the performance oflowering the TC.2. The long-term effect of Danlou tablets on regulation of serum lipid and itsantioxidant effect in hyperlipidemia rabbit: Comparison of model control group can befound after4weeks intervention, serum TC TG, LDL-C content has a significantdecrease in Danlou tablet (2g/kg) group (P <0.05), lipid-lowering effect reach to the peakin12weeks; detection of serum lipoprotein oxidation degree show that, to12weekends,LDL oxidation degree in Danlou tablet group is significantly lower than the model controlgroup (P <0.05).3. The impact of Danlou tablets on atherosclerotic lesions in hyperlipidemia rabbitmodel: Compared with model control group, after20weeks of continuous intervention，Danlou tablet group animal carotid plaques in load area decreased to10%significantly (P<0.05), from local plaques and systemic atherosclerosis disease in comprehensive analysis,the progression of AS disease in Danlou tablet group was obviously lighter than modelcontrol group (P<0.05), and is superior to the conventional dose of atorvastatin.4. Danlou tablets regulate liver lipid metabolism and the plaques MDA content inhyperlipemia rabbit: End point detection of each animal liver lipid levels, liver cholesteroland triglyceride levels in Danlou tablet group were significantly lower30%than the modelcontrol group (P <0.05); Compared to the statin group, liver expression of HMG CoAreductase,7-hydroxylase (CYP7A1) in Danlou tablet group have no obvious inhibition (P<0.05); the expression of liver glucose6phosphatase (G-6-P) and acetyl CoAcarboxylase (ACC) reduced50%both significantly (P <0.05); Compared with modelcontrol group, ileal bile acid transporter expression in Danlou tablet group reduced20%significantly (P <0.05), and finally to detect each animal artery plaque oxidized lipoproteinreceptor expression and MDA content and found that compared with model control group,the expression of lectin oxidized low density lipoprotein receptor (LOX-1) significantlyreduced, HDL receptor (SR-BI) expression significantly elevated (P <0.05) and MDAplaques were significantly reduced50%(P <0.05) in Danlou tablet group. Conclusion:1. Compared with rosucastatin, high dose of Danlou tablet can rapidly reduce thecontent of serum cholesterol and triglyceride, and at the same time small dose maintain forshort periods also has similar lipid-lowering effect.2. In Danlou tablets (2g/kg) intervention4weeks, that is evident of lowering serumTC, TG, LDL-C, and more stable lipid-lowering effect than statin (1mg/kg); Interventionin12weeks, show the obvious effect on LDL oxidation.3. After20weeks long-term intervention，experimental result show that Danlou tablet(2g/kg) not only reduce carotid atherosclerotic lesions significantly, also can delaysystemic atherosclerosis progress, the function cure atherosclerosis is more better thanstatin (1mg/kg), as for this effect may be related to its regulation lipoprotein receptorexpression and its antioxidant mechanism closely.4. End experimental findings, Danlou tablets group have significantly lower livercholesterol and triglyceride levels, serum-lipid lowing effect does not cause liver lipiddeposition and does not affect the sugar and lipid normal metabolism, and itscholesterol-lowering action is not inhibit liver HMG CoA reductase-play, may be relatedto inhibiting the intestine bile acid transporter gene expression.