Establishment of Rat Model of Coronary Heart Disease with Xinxueyuzu(心血瘀阻)Syndrome and Evaluation of Prescription Efficacy
Objective:To investigate the pathological features of the model established by left anterior descending coronary artery ligation and the in-tervention effect of Xuefuzhuyu(血府逐瘀)Decoction,and explore the establishment method of Xinxueyuzu(心血瘀阻)Syndrome based on the theory of prescription corresponding to syndrome.Methods:A rat model of coronary heart disease was established by left anterior de-scending coronary artery ligation.Rats were randomized into normal control,sham surgery,model control,Xuefuzhuyu Decoction(14 g/kg),and trimetazidine(5.4 mg/kg)groups.All the rats were administered with corresponding drugs by gavage for 14 days.A tongue color analy-zer was used to determine the R(red),G(green),and B(blue)values of the tongue.The heart rate and ST segment changes were observed by electrocardiogram(ECG)measurement.Echocardiography was employed to determine the left ventricular ejection fraction(LVEF),left ventricular fractional shortening(LVFS),left ventricular end-systolic diameter(LVIDs),and left ventricular end-diastolic diameter(LVIDd).The whole blood viscosity,Casson viscosity,and red blood cell aggregation index were determined.Hematoxylin-eosin(HE)stai-ning and Masson's staining were performed to observe histopathological changes and myocardial fibrosis,respectively.Image J was used to calculate the collagen volume fraction(CVF).Transmission electron microscopy was employed to observe the ultrastructural changes in myo-cardial cells.Enzyme-linked immunosorbent assay(ELISA)was employed to measure the serum levels of thromboxane B2(TXB2),6-keto-prostaglandin F1α(6-keto-PGF1α),plasminogen activator inhibitor-1(PAI-1),and tissue-type plasminogen activator(t-PA).Immunohisto-chemistry(IHC)was employed to assess the positive expression of intercellular adhesion molecule-1(ICAM-1)and vascular cell adhesion molecule-1(VCAM-1)in the myocardial tissue.Results:Compared with the normal control group and the sham surgery group,the model control group showed decreases in tongue R,G,and B values(P＜0.01),increases in heart rate and ST segment elevation(P＜0.01),lowered LVEF and LVFS(P＜0.01),and elevated LVIDd and LVIDs(P＜0.01).The histopathological examination of the model control group re-vealed disarrangement of myocardial cells,extensive infiltration of inflammatory cells,increased collagen fibers,and elevated CVF(P＜0.01).The mitochondrial membrane and ridge structures exhibited swelling,fragmentation,dissolution,and visible vacuolar changes.Moreover,the model control group showed increased whole blood viscosity(low,medium,and high shear),Casson viscosity,and red blood cell aggregation index(P＜0.01),elevated levels of TXB2 and PAI-1(P＜0.01),lowered levels of 6-keto-PGF1α and t-PA(P＜0.01),and increased posi-tive expression of ICAM-1 and VCAM-1 in the myocardial tissue(P＜0.01).Compared with the model control group,the Xuefuzhuyu Decoc-tion group showed increased tongue R,G,and B values(P＜0.01),decreased heart rate and ST segment elevation(P＜0.01),lowered LVIDd and LVIDs(P＜0.01),and elevated LVEF and LVFS(P＜0.01).The histopathological examination revealed regular arrangement of myocar-dial cells,significant reduction in myocardial gap,mild infiltration of inflammatory cells,decreased collagen fibers,and reduced CVF(P＜0.01).The degree of swelling,fragmentation,dissolution,and vacuolar changes in mitochondrial membrane and ridge structures was allevia-ted.Furthermore,the Xuefuzhuyu Decoction group showed decreased whole blood viscosity(low,medium,and high shear),Casson viscosity,and red blood cell aggregation index(P＜0.01),lowered levels of TXB2 and PAI-1(P＜0.01),elevated levels of 6-keto-PGF1α and t-PA(P＜0.01),and inhibited positive expression of ICAM-1 and VCAM-1(P＜0.01).Conclusion:The modeling by the left anterior descending coronary artery ligation leads to the pathological features such as cardiac dysfunction,myocardial structural damage,sticky blood coagulation,purple tongue,vascular endothelial injury,fibrinolysis system disorder,and adhesion factor deposition.The above changes can be adjusted by Xuefuzhuyu Decoction,a representative prescription with the Huoxuehuayu(活血化瘀)effect.The combination of evaluation and disproof can well simulate the pathological process of Xinxueyuzu syndrome in coronary heart disease.
Coronary heart diseaseXinxueyuzu(心血瘀阻)syndromeCombination of disease and syndromeXuefuzhuyu(血府逐瘀)Decoction
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