| ObjectivesTo investigate the effect and possible mechanism of the derivative of cordycepin attenuates - Triacetyl-3-hydroxyphenyladenosine on early atherosclerosis of apoE-/- mice ,in order to provide scientific basis for the prevention and treatment of the early atherosclerosis.MethodsChoose fifty-one male ApoE-/- mice from The Chinese academy of medical sciences institute of experimental animals for this experiment. At the fifth week,the mice were divided randomly into five groups:Model control group(n=11); simvastatin group(5mg/kg/d)(n=10);THPA treatment groups(2.5,5,10 mg/kg/d)(n=10,each group of ten only).All of the groups of experimental animals were separatedly fed with high-fat diet(15.8% fat and 1.25% cholesterol,the fodder were bought from Beijing HuaFuKang biological technology Co,LTD), carboxyl methyl cellulose addng solvent, simvastatin and THPA for six weeks.All of the carboxyl methyl cellulose, simvastatin and THPA were given to the experimental animals by gastric lavage.After the treatment of six weeks,fasted for 12 hours and anesthesia,the serum lipid TC,HDL-C,LDL,TG were measured by angular artery blood sampling with the methods of ELISA;the arcus aortae and aortic root were taken for estimating the patch size by oil red O dyeling.The heart aortic root near the bottom part were used for continuous frozen section production. The thickness of the frozen section was eight micron,slice the site began with the aortic root until the aortic valve disappeared completely.Collect 45 slices of each animal averagely,extract five tickets for oil red O dyeing and bright green after dyeing,calculate the positive area of lipid dyeing(μm2),analyze the plaque areas by quantitative staticstics throuth Image-Pro Plus software 4.5. The remaining 40 slices of the bottom part of heart aortic root were used for immunohistochemistry,in order to detect the expression of the factors related to inflammation such as VCAM-1,TF,LOX-1,NF-κB,and also the factors related to endothelial protection such as iNOS and eNOS. All data analysis were realized by using the SPSS 13.0 software.Results1.serum lipids:Compared with the model control group,no significant levels change of plasma TC,TG and LDL were found after the THPA treatment of sis weeks,however,the levels of plasma HLD were significantly changed compared with the model control goup(P<0.01).2.the oil red O dyeing of aortic arch lining:Different doses of THPA treatment group were significantly inhibit the formation of atherosclerotic plaque,compared with the model control group, the disease areas of 2.5,5.0 and 10 mg/kg THPA treatment group were reduced about 47%,45% and 43%.3.the results of the oil red O dyeing of the heart aortic:Compared with the model control group,the doses of THPA about 2.5,5.0 and 10mg/kg were significantly inhibit the formation of atherosclerosis,the plaques were respectively reduced about 40%,33% and 35%.4.the factors related to inflammation:After the treatment of THPA,the expression of the factors related to inflammation such as VCAM-1,TF,NF-κB and LOX-1 were decresed obviously compared with the model control group(P<0.01),no obvious differences were found between the simastatin group and the THPA treatment group also between the THPA group with different doses(P>0.05).5.the factors related to endothelial protection(iNOS,eNOS):The iNOS expression of THPA treatment group were obviously lowere than model group(P<0.01),but the expression of eNOS were higher than model group(P<0.01),no obvious differences were found between the group of simastatin and the THPA treatment group also between the THPA group with different doses about the expression of iNOS and eNOS(P>0.05).Conclusions1. THPA can reduce the atherogenesis effectively and play a role by affecting various ways of the atherogenesis in apoE-/- mice.2. Inhibit inflammation and protect vascular endothelium maybe the possible mechanisms of THPA on early atherosclerosis in apoE-/- mice,thus for THPA within good therapeutic effect on early atherosclerosis in apoE-/- mice.3. Our experimental results provide the new understanding for the function of preventing atherosclerosis, providing the scientific basis for development and application of THPA drugs. |
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