Clinical Observation And Experimental Study On The Treatment Of Atherosclerosis Based On Invigorating Spleen Turbidimetric Method

Objective:To investigate the clinical efficacy of Shuangyao Tiaozhi Decoction（SYTZD）against atherosclerosis（AS）with spleen deficiency and dampness excess,to assess the effectiveness and safety of the formula guided by the method of strengthening the spleen and removing turbidity,and to further investigate the effects and potential mechanisms of SYTZD on abnormal lipid metabolism in ApoE^-/-mice fed on a high-fat diet,which will provide a theoretical basis and scientific support for the clinical treatment of atherosclerotic diseases with SYTZD.Methods:Clinical study:80 cases were collected with a diagnosis of AS and randomized into a treatment group and a control group,40 cases each.Both groups received conventional treatment and rosuvastatin.On the basis of conventional treatment,the treatment groups were simultaneously administered SYTZD.The course of treatment was90 days.The serum lipid contents,hypersensitive C-reactive protein（hs-CRP）levels,intima-media thickness（IMT）and plaque area of patients in the 2 groups were evaluated before and after treatment.Experimental study:10 of the 50 SPF ApoE^-/-mice were randomly selected to be fed normal diets as the control group（C group）and the rest were fed high-fat diets.After 6 weeks of successful modelling,mice fed high-fat diets were randomized into high-fat diet group（M group）,simvastatin group（S group）,low-dose SYTZD group（L-S group）and high-dose SYTZD group（H-S group）using the random number table method.All mice were administrated for consecutive 8 weeks.Serum TC,TG,LDL-C and HDL-C contents were determined biochemically.Liver histopathological and morphological changes were detected using HE staining,and hepatic lipid deposition was detected by oil red O staining.The mRNA and protein expressions of liver fatty acid synthase（FAS）,acetyl Co A carboxylase（ACC）,and peroxisome proliferators-activated receptorα（PPARα）were detected using RT-q PCR and Western blot.Results:Clinical study:At the end of treatment,patients in both groups had improved atherosclerotic disease,reduced carotid IMT and plaque area,reduced lipid（TC,TG,LDL-C）and serum hs-CRP levels,and increased HDL-C levels（P<0.05,P<0.01）.Experimental study:mice in the M group had significantly higher contents of serum lipids（TC,TG,and LDL-C）,more hepatic steatosis,higher expressions of FAS and ACC,and lower expression of PPARα（P<0.01,P<0.0001）.Compared with the M group,mice treated with SYTZD showed significantly reduced lipid contents（TC,TG,and LDL-C）,significantly improved liver steatosis,decreased the expressions of FAS and ACC,and increased the expression of PPARα（P<0.05,P<0.01,P<0.001,P<0.0001）.The improvement effect of H-S group on abnormal lipid metabolism was superior to that of L-S and S groups（P<0.05,P<0.01）.Conclusion:SYTZD could reduce blood lipid and serum hs-CRP levels,reduce carotid IMT and plaque area,and significantly improve clinical symptoms in traditional Chinese medicine in patients with AS.Its mechanism might be through regulation of hepatic FAS,ACC and PPARαprotein expression,inhibition of hepatic lipid de novo synthesis and enhancement of lipid oxidation,thus exerting a hypolipidemic effect.