Study On The Effect And Mechanism Of Dazhuhongjingtian Capsule On Improving Atherosclerosis In LDLR-/-mice Based On Oxidative Stress

Background and ObjectiveWith the development of society and the improvement of people's living standards,the number of deaths caused by cardiovascular and cerebrovascular diseases caused by atherosclerosis(AS)has increased,which has become the first cause of death in the global population.According to AS's"lipid theory"theory,the formation of AS is closely related to the accumulation of intravascular cholesterol.Therefore,lipid-lowering therapy has become an important treatment for prevention and control of AS progression,but clinical studies have shown that patients with atherosclerosis There are 40%of normal blood lipids,and 70%of patients with AS with lipid-lowering standards have cardiovascular events.In recent decades,signal transduction and gene regulation research shows that the level of Oxidative Stress(Oxidative Stress,OS)is a key factor in atherosclerosis occurs,formed from fatty streaks to plaque rupture and thrombosis is a main cause of atherosclerosis development process,and resistance to Oxidative Stress become important targets for the treatment of atherosclerosis[2].At present,the main antioxidant enzymes are mainly heme oxygenase-1,quinone oxidoreductase,superoxide dismutase 1,superoxide dismutase 2,catalase to fight OS.Therefore,we can find a new anti-atherosclerosis pathway by activating the expression of antioxidant enzymes.TCM holds that the pathologic factors such AS"phlegm,blood stasis and toxin"are closely related to the formation and development of AS."All kinds of diseases are caused by qi"in su wen · ju tong lun,qi is the leading factor of blood circulation,qi is the leading factor of blood circulation,qi deficiency is the leading factor of blood circulation,blood stasis is the hindering factor of heart and vein,heart and vein loss,qi deficiency and blood stasis are interrelated with the development of AS.Rhodiola rosea capsule is often used in clinical treatment of coronary heart disease,the main drug ingredient in the capsule rhodiola rosea has the effect of invigorating qi,activating blood circulation and relieving pain.So this experiment will by feeding high-fat diet LDLR-/-mice caused by atherosclerosis model,with large strain of rhodiola capsule after the intervention,oil red staining and aortic vascular ultrasound,biochemical test,the research methods such as Westernblotting,preliminary discussion whether big plant rhodiola capsule can be through the oxidative stress to inhibit the formation and development of atherosclerosis,and discuss its possible mechanism.To provide a basis for clinical treatment of AS and coronary heart disease.Methodwe selected 45 male LDLR-/-mice aged 7 weeks and randomly divided into 3 groups,namely,normal diet group(STD),high-fat diet group(HFD),and large rhodiola capsules treatment group(SAL),with 15 mice in each group.STD group was fed with standard diet,while HFD group and SAL treatment group were fed with high-fat diet for 10 weeks.SAL treatment group mice were treated with rhodiola rosea capsule gavage,with distilled water as the solvent to dissolve rhodiola rosea capsule.The gavage dose was 0.7g/kg once a day,and the mice in other groups were given normal saline gavage of the same volume.After 10 weeks of continuous administration,5 mice in each group were randomly selected for microultrasound imaging of aortic arch plaques.Determination of the type lipid levels(including serum TC,TG,LDL,HDL-C-C),the whole aorta section and the aortic arch three bifurcation section of oil red staining to observe plaque formation,with commercial kits in mice serum and aorta tissue malondialdehyde(MDA),CAT and gsh-px and SOD activity,the aorta in Westernblotting testing organization in CAT and gsh-px,SOD protein levels.Results(1)Oil red staining of the aortic section of the mouse showed that the area of aortic plaque in the HFD group was significantly larger than that in the STD group,suggesting that the atherosclerosis model was successful.After the intervention of Dazhu Hongjingtian capsule,the SAL group The plaque area was significantly improved compared with the HFD group.Dazhuhongjingtian capsule can effectively inhibit the formation of atherosclerotic plaque in LDLR-/-mice induced by high fat feeding.(2)The plaque area at the beginning of the brachiocephalic artery was measured by high-resolution ultrasound biomicroscopy.The plaque area of the HFD group was significantly larger than that of the STD group.After intervention by Dazhu Hongjingtian capsule,the SAL group was compared with the HFD group.The mice showed a significant reduction in plaque area.(3)The results of blood lipid determination showed that the levels of TC,TG and LDL-C in LDLR-I-mice were significantly increased after high-fat diet,and the level of HDL-C was significantly decreased.After treatment with Dazhuhongjingtian capsule for 10 weeks,observation Serum total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-C)and high density lipoprotein cholesterol(HDL-C)levels were significantly improved in the SAL group relative to the HFD group.(4)The activity of malondialdehyde(MDA),CAT,GSH-PX and SOD in serum and aortic tissues of mice was determined by commercial kit.The results showed that after 10 weeks of treatment with Dazhuhongjingtian capsule,MDA The level has been significantly improved.In addition,the intervention of Dazhu Hongjingtian Capsule significantly increased the activity of SOD,CAT and GSH-PX in serum and aorta of LDLR-/-mice.(5)The levels of CAT,GSH-PX and SOD in aortic tissue were detected by Western blotting.The results showed that the levels of CAT,GSH-PX and SOD in HFD group were significantly lower than those in STD group,while CAT and GSH-PX in SAL treatment group.The level of SOD protein was significantly higher than that of the HFD group,and the protein level was slightly lower or substantially flat compared with the STD group.ConclusionDazhu Hongjingtian Capsule can inhibit the level of oxidative stress by interfering with related enzymes in oxidative stress,and ca n improve the level of lipid metabolism in mice and reduce the content of low-density lipoprotein cholesterol in blood.The occurrence and development of hardening has a certain inhibitory effect.