| Objective:To expand the indications of Yixinjiedu formula, and to confirm its benefits in Heart Failure With Preserved Ejection Fraction (HFpEF) patients, we used the animal experiment to study the effects of Yixinjiedu formula on diastolic function in rats. It is common in clinic that traditional Chinese Medicine (TCM) is applied based on the treatment of western medicine. Thus, in this study, Yixinjiedu formula was combined with Fosinopril to illustrate the concomitant efficacy. Further aims were to explain the therapeutic principle ’Tonifying Qi’ ’Blood Activating’ and ’Detoxication’ in Traditional Chinese Medicine(TCM)based on remodeling and angiogenesis theory.Methods:1. A retrospective, noncomparative study designed to evaluate the heart diastolic function in coronary heart disease (CHD) patients in hospital. And investigate the TCM syndrome distribution in those CHD patients with diastolic dysfunction.2. SD rats were subjected to either proximal left anterior descending coronary artery (LAD) ligation or sham operation to establish the heart failure model. Rats’syndrome was evaluated by electrocardiogram (ECG) and divided into 10 groups-sham operation group, model group, YXJDF high, medial, low dose groups, QSYQ group, QLQX group, fosinopril group, digoxin group and combination group.3. After 28 d postoperatively, the ultrasonic echocardiography, hemodynamics were introduced to rats’basic vital signs, heart instruction and function evaluation.4. Pathological dyeing, blood biochemical test and fibrinogen (FiB) test were introduced to evaluate the efficacy and the safety of Yixinjiedu formula.5. The possible key node molecular which is closely related to Yixinjiedu formula is investigated by literature research, and then molecular biology techniques such as Western Blot (WB), Polymerase Chain Reaction (PCR) were applied to detect these proteins.Results:1.599 patients were included in this study.62 (10.9%) patients EF< 50%; whereas 496 (87.6%) EF≥50%.213 (37.6%) patients E/A< 0.8 or> 1.5; whereas 161 (28.4%) patients 0.8≤E/A< 1.5.361 (59.2%)patients had the description of diastolic dysfunction,24(4.2%) patients had the description of abnormal heart function; whereas 59 (10.4%) patients had the description of normal heart function.2. Evaluations of the diastolic function in heart failure rats:compared with sham operation group, the MV Decel Time (P< 0.05), Tei index (P< 0.01), E/E’ ratio (P< 0.01), left ventricular end-diastolic pressure (LVEDP) (P< 0.01) in model group were significantly increased, the absolute value of-dp/dtmax (P< 0.01) in model group was decreased, all the figures above indicate that there was diastolic dysfunction in this heart failure model.3. Comparative evaluation of TCM and Western medicine on the efficacy on the diastolic function:compared with the model group, E/E’ ratio (P< 0.01), LVEDP (P< 0.01) in the fosinopril group were significantly decreased, the absolute value of -dp/dtmax (P< 0.01) in model group was increased; LVEDP in the digoxin group were significantly decreased (P < 0.05). Other improved parameters about diastolic function were absent in this study. Nevertheless, all the TCM treatment groups, no matter the differences in doses, could improve all the parameters related to the diastolic function dramatically, and they were superior to western medicine in this study.4. Comparative evaluation of Yixinjiedu formula and other treatments on the efficacy on the diastolic function:Yixinjiedu formula high dose and low dose group could decrease the MV Decel Time significantly in the compare with the model group, while other treatmented groups had no difference with the model group. Yixinjiedu formula high dose(P< 0.01) and medial dose group (P< 0.05)could decrease the E/E’ ratio in the comparison with the model group, while other treatmented groups had no difference with the model group. All the Yixinjiedu formula treatment groups had lower LVEDP and higher the absolute value of dp/dtmax than the model group, but the improvement of Qishenyiqi pill on those two parameters were much bigger.5. Efficacy evaluation of the combination treatment (Yixinjiedu formula medial dose combined with fosinopril):Compared with the model group, the combination treatment group (P< 0.01) and the digoxin group (P< 0.01) could improve the degree of changes on Left Ventricular Posterior Wall (LVPW) and they could also raise the EF and FS (P< 0.05), while the combination treatment group had better improvements. All the treatmented groups could increase the LVSP (P< 0.01) and +dp/dtmax (P< 0.01), and there was no difference in those treatmended groups (P> 0.05)Except the digoxin group, all the treatmented group could lower the LVEDP and higher the absolute value of -dp/dtmax (P< 0.01). Moreover, Yixinjiedu formula high dose, combination treatment and fosinopril group were much better than other groups. The heart weight to body weight ratio (HB/WB) was also improved in the combination treatment group and fosinopril group, and they had significant difference with the model group (P< 0.01)The combination treatment group and fosinopril group could down-regulate lactate dehydrogenase (LDH) (P< 0.01). The combination treatment alone could lower the serum creatine kinase (CK) (P< 0.05). Also, except digoxin group, all the other treatmented groups could decrease the creatine kinase isoenzyme (CK-MB), and what’s more, the combination treatment group and fosinopril group has the best effect (P< 0.01).Compared with the model group, the serum fibrinogen (FIB)in combination treatment group was dramatically declined (P< 0.01)It was illustrated in the Mallory method dying myocardial pathological slice:myocardial necrosis was happened in model group rats’ hearts, where the collagenous fiber tissue diffused in the normal myocardial tissue and replaced the normal one. All the treatmented groups could improve this situation in different degrees, while Yixinjiedu formula high dose and combination treatment groups had better efficacy than digoxin group.6. Effect of the combination treatment on the heart failure rats’ basic vital signs:There was no difference between all the groups (P> 0.05). Fosinopril group and digoxin group could increase the heart rate (P< 0.05)7. Effect of the combination treatment on the heart failure rats’ liver function:Compared with other groups, the level of alanine aminotransferase (ALT) in fosinopril group was increased (P< 0.01). And the level of aspartate aminotransferase (AST) in fosinopril group (P< 0.05) was significantly increased, compared with sham operate group.8. The possible key node molecular of Yixinjiedu formula:Compared with the sham operated group, the CD31 expression of the heart tissue around the scar in model group was significantly decreased (P< 0.01), while Yixinjiedu formula medial dose (P< 0.05), low dose (P< 0.01) and Qiliqiangxin capsule group (P< 0.05) could increase the CD31’s expression in myocardial tissue.It was showed in the WB that, compared with the sham operated group, the SMA-a expression of the heart tissue around the scar in model group was significantly increased (P < 0.01); And all the treatment groups could decrease the expression of CD31 (P< 0.01) While in the PCR results, only the Yixinjiedu formula low dose group could lower the expression (P< 0.05)The vWF expression was increase in the model group both in WB and PCR results, compared with the sham operate group (P< 0.01). It was clear to see that Yixinjiedu formula high dose(P< 0.05), medial dose(P< 0.01), low dose(P< 0.05) and combination treatment group (P< 0.05) could decrease the expression of vWF in the WB results.The expression of CD34 in the model group was similar to that of sham operate group(P > 0.05). And Yixinjiedu formula medial dose group could decrease the expression of CD34, compared with sham operated group (P< 0.01)and model group(P< 0.05). compared with the sham operated group, the expression of VEGF in the model group(P< 0.05), high dose group(P< 0.05), combinational group(P< 0.01) were dramatically increased; while the expression of VEGF in low dose group was lower than that in model group (P< 0.01) and other treatmented groups(P< 0.05).Conclusion1. There were diastolic dysfunction in most CHD patients, and most common syndrome in those patients were Qi Deficiency and Blood Stasis.2. Yixinjiedu formula could improve the diastolic function in Heart Failure Rats. The mechanism maybe it can inhibitate the inflammatory factors caused by myocardial ischemia and the hyperplasia of interstitial fibers in heart failure rats, and decrease renin and Angll level, as well as improve the energy metabolism, regulate the neuroendocrine and protect the endothelial function. So that the left ventricular stiffness is lowered, the left ventricular relaxation is increased and myocardial contraction is reserved.3. When combined with Yixinjiedu formula, the efficacy of fosinopril on the improvement of heart function grew. Moreover, the combination treatment had no side effect on the blood pressure, heart rate and liver function.4. It was illustrated in the mechanism research that ① Yixinjiedu formula had the anti-fibrosis and angiogenesis around the scar tissue functions, it also could protect the vascular endothelium. ②The therapeutic principle ’Tonifying Qi’ ’Blood Activating’ could be related to angiogenesis mechanism. ③The therapeutic principle ’Tonifying Qi’ ’Detoxication could be related to remodling mechanism and diastolic function.④With the increase of the dose, the TCM effect of Yixinjiedu formula changed from ’tonifying qi’ ’activating blood’ to ’activating blood’ ’detoxification’. |
PDF Full Text Request