| Objective: To observe the protective effect of Qiliqiangxin capsule on heart failure after myocardial infarction of rabbit and explore its possible mechanism.Methods: Total 76 adult healthy New Zealand rabbits were selected randomly 64 of them to dissect the chest to ligate left anterior descending branch to establish acute myocardial infarction(AMI) model,54 of them were successfully built into model , and the other 12 were treated as the sham-operated group(only playing a loose knot under the coronary artery in the sham-operated group), 2 weeks after operation , we selected four rabbits from each of the AMI model group and sham-operated group by random for Doppler echocardiography examination and invasive hemodynamic measurement to prove that the rabbit heart failure model after myocardial infarction were established successfully , So at time of 2 weeks after operation , we randomly divided the myocardial infarction rabbits (remaining 50) into in control group of heart failure after myocardial infarction (MI-C group), enalapril treatment group(MI -E group), high-dose Qiliqiangxin capsule treatment group (MI-QH group), median-dose Qiliqiangxin capsule treatment group(MI-QM group), low-dose Qiliqiangxin capsule treatment group (MI-QL group) ,there are 5 groups, 10 rabbits in each group; there are 8 rabbits in sham-operated group(Sham group),a total of six groups, MI-E group's rabbits were given enalapril 5mg/kg/d, MI-QH group's rabbits were given dry powder of Qiliqiangxin capsule 0.6g/kg/d, MI-QM group's rabbits were given dry powder of Qiliqiangxin capsule 0.3g/kg/d, MI-QL group's rabbits were given dry powder of Qiliqiangxin capsule 0.15g/kg/d, all drugs are dissolved with normal saline into 2ml solution for intragastric adminstration,only give 2ml normal saline for intragastric administration in MI-C group and Sham group. Continuous administered for four weeks, the following parameters were measured after 4 four weeks:1,non-invasive ultrasonic testing: Two-dimensional ultrasound measured of left ventricular ejection fraction (LVEF), left ventricular end systolic diameter (LVDs) and left ventricular end diastolic diameter (LVDd), The maximum of early diastolic and late diastolic filling velocity of left ventricular: E peak and A peak (E, A). Doppler tissue imaging (DTI) measured the contraction velocity (Sa) of left ventricular anterior, septal and lateral wall.2,invasive hemodynamic testing: PICCO monitor measured cardiac index (CI), cardiac function index (CFI), extravascular lung water index (EVLWI), heart rate (HR), cardiac function index (CFI), intrathoracic blood volume index (ITBVI) and other parameters.3,rabbits were killed after the above testing is completed, immediately dissect chest to extraction the heart, at the level of cardiac infarction along the long axis perpendicularly chop heart into two parts, the upper part is used to do common pathological section to carry out hematoxylin eosin stain and Van Gieson stain; then divided the other part into two parts, one part immediately embed into the electron microscopy fixative to fixed and then produced microscope specimens to observe under the electron microscopy, take the border zone of myocardial infarction of the other part into freezing tubes, immediately placed in -80℃ultra-low temperature refrigerator for test ofα-MHC,β-MHC mRNA.Results: 1,Four weeks after administration , seven rabbits were survived in both Sham group and MI-C group, eight rabbits were survived in MI-E group, eight rabbits were survived in MI-QH group, seven rabbits were survived in MI-QM group, seven rabbits were survived in MI -QL group.2,Cardiac function results test by echocardiography and DTI: MI-E group's, MI-QH group's and MI-QM group's LVEF, E/A, anterior and lateral contraction speed were significantly superior to MI-C group's (P <0.05); MI-QH group's, MI-QM group's and MI-QL group's LVEF, E/A, anterior contraction speed were significantly different from each other. (P <0.05)3,Hemodynamic results test by PICCO: MI-E group's, MI-QH group's and MI-QM Group's CI, CFI were significantly superior to MI-C group's (P <0.05); while MI-E group's, MI -QH group's and MI-QM Group's HR, EVLWI, ITBVI were significantly lower than MI-C group's(P <0.05); MI-QH group's, MI-QM group's and MI-QL group's HR, CI , CFI, EVLWI, ITBVI were significantly different from each other. (P <0.05)4,Pathological results: MI-E group and MI-QH group, MI-QM group were significantly inhibited scar formation and reduced collagen hyperplasia after acute myocardial infarction , and their myocardial cells were arranged in neat rows, structurally-complete, protecting mitochondrial structure in ultrastructure, making sarcomere arranged in neat rows, MI-QH group was superior to MI-QM group, while the MI-QL group had no significant protective effect.5,RT-PCR results: Expression levels ofα-MHC mRNA of the MI-E group,MI-QH group and MI-QM group were significantly higher than the MI-C group (P <0.05); Expression levels ofβ-MHC mRNA of the MI-E group,MI-QH group,MI-QM group were significantly decreased than MI-C group (P <0.05);α- MHC /β-MHC mRNA ratio in the MI-E group, MI-QH group were significantly higher than MI-C group (P <0.01), MI-QH group was slightly higher than MI-QM group, but there is no significant difference in statistics, MI-QM group was higher than MI-QL group, there is significant difference (P <0.05).Conclusions:1,Qiliqiangxin capsule can improve cardiac function and hemodynamic of heart failure after myocardial infarction of rabbits., these is a relevance between its improvement and its dose, high-dose group was better than medium-dose group, middle dose group was better than low-dose group, the improvement of high dose group is equal to ACEI drugs enalapril, low-dose group's improvement on cardiac function and hemodynamic is not obvious.2,Qiliqiangxin capsule can inhibit ventricular remodeling of heart failure after myocardial infarction of rabbits, the degree of inhibition is increased with the dose increased , MI-QH group is the most obvious and it is not worse than even superior to MI-E group, MI-QM Group take second place, MI-QL group have the weakest inhibition.3,Qiliqiangxin capsule not only can improve cardiac function and hemodynamic ,but also can inhibit ventricular remodeling, its possible mechanism is that it can promote the expression ofα-MHC mRNA, inhibit the expression ofβ-MHC mRNA, and finally increasedα-MHC /β-MHC mRNA ratio. |
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