Effect Of Yiqi Huoxue Decoction On Left Ventricular Hypertrophy And The Cardiac Myocyte Apoptosis In Left Ventricle Of Spontaneously Hypertensive Rats

Objective: By means of observing the effects of yiqi huoxue decoction indifferent dosages and nifedipine on left ventricular hypertrophy, the cardiac myocytes' apoptosis and the morphological changes of myocardium in left ventricle of spontaneously hypertensive rats(SHRs), this research aims to explore the prevention and treatment mechanisms of yiqi huoxue decoction to left ventricular hypertrophy induced by essential hypertension.Methods: Fourteen-week-old male SHRs were divided randomly into 5 groups:SHR-C(untreated), SHR-X(treated with nifedipine), SHR-Y1(treated with high dose of yiqi huoxue decoction), SHR-Y2(treated with moderate dose of yiqi huoxue decoction), SHR-Y3(treated with low dose of yiqi huoxue decoction). Each group consisted of 8 rats. We measured the systolic blood pressure(SBP) before treatment and we did the same job during treatment every four weeks. After 8 weeks treatment, all rats were killed. Heart weight index(HWI), left ventricular mass index(LVMI) were calculated. Combined with automatic imaging analysis technique, cardiac myocytes' apoptosis in left ventricle was detected by using in situ terminal deoxynucleotidyl transferase mediated dUTP nick end labeling(TUNEL) staining. The morphological and structural changes of myocardial cells in left ventricle of SHRs were observed with light microscope and transmission electron microscope.Results:1. The SBP of SHRs in SHR-C rose gradually while rats grew. After 8 weeks treatment, compared each treatment group with SHR-C, the SBP was decreased significantly(P < 0.01); compared SHR-Y1, SHR-X with SHR-Y3 respectively, the decrease was significant too(P<0.05); while compared SHR-Y1, SHR-Y2 with SHR-X respectively, the SBP had no statistical difference(P>0.05); and the SBP had no significant difference among other treatment groups(P>0.05).2. Compared SHR-Y1, SHR-Y2 and SHR-X with SHR-C respectively, HWI, LVMIand CMAI decreased significantly(P < 0.05 or 0.01); while there was no significant difference between SHR-Y3 and SHR-C(P>0.05). The LVMI and CMAI of SHR-Y1 had significant decrease to those of SHR-Y3(P<0.05); The HWI, LVMI and CMAI of SHR-X had no significant difference to those of SHR-Y1, SHR-Y2 and SHR-Y3(P>0.05); and there was no significant difference among other treatment groups(P>0.05).3. The results under light microscope were: In SHR-C, cardiac muscle fibers were swollen or disrupted with unclear interspace or disorganized arrangement, and there was a large area of myocardium's obvious hydropic degeneration, as well as some hypertrophic nuclei or pyknosis of myocardial cells. The results under transmission electron microscope(TEM) were: The apoptotic cardiac myocytes which had apoptotic ultrastructural features could be found in the left ventricular tissue obtained from SHR-C group. The changes of nucleus, which was the most significant change of apoptotic cardiac myocytes were as follows: nuclear membrane shrank and nuclear chromatin condensed and congregated under nuclear membrane like speckle, abutting against the nuclear envelope; some nucleoli disappeared, we observed pyknosis by chance. Mitochondria of some myocardial cells were markedly swollen with some disorganized or disrupted mitochondrial cristae which displayed like uneven vacuole. Compared with SHR-C, the above-mentioned pathological changes of SHR-Y1 were less obvious; the pathological changes ameliorated slightly in SHR-Y2 and SHR-X; but there was no significant improvement in SHR-Y3. The treatment effect of SHR-Y1 was better than that of SHR-X, while there was no significant difference between SHR-Y2 and SHR-X.Conclusion:1. With the increase of weekly age, the blood pressure of SHRs rose gradually, and LVH came into being and developed gradually.2. Yiqi huoxue decoction and nifedipine can reduce the SBP, LVMI and HWI of SHRs significantly, and there was no significant difference between the two groups. The above-mentioned effects of yiqi huoxue decoction increased with the increase of dosage. The reduction of SBP might be one of the important mechanisms by which yiqi huoxue decoction prevents and reverses LVH.3. Yiqi huoxue decoction and nifedipine could slow down the damages of left ventricle in SHRs during the process of LVH. The effects of yiqi huoxue decoction increased with the increase of dosage.4. Yiqi huoxue decoction and nifedipine could inhibit the cardiac myocytes' apoptosis in left ventricle, and there was no significant difference between the two groups. The effects of yiqi huoxue decoction increased with the increase of dosage. The inhibition of the cardiac myocytes' apoptosis in left ventricle during the process of LVH might be another important mechanism by which yiqi huoxue decoction prevents and reverses LVH.