| Purpose:Through establishing chronic heart failure rat models ,we observe the influence of chronic heart failure rat models MMP-1 and TIMP-1 by the benefiting Qi and activating Blood compound prescription, research the mechanism of action and targets from the gene, protein and histological aspects, to clear the mechanism of resistance to ventricular remodeling and provide the scientific basis of chronic heart failure for the prevention and treatment of Chinese medicine.Material and method:1. Create chronic heart failure (CHF) rat model by ligating coronary artery with exhaustive style swimming , hunger and other methods, then detecte ejection fraction (EF)≤60% and so on by Doppler echocardiography, and the status of the rats, determine the success of the modeling.2. The successful models were divided into traditional Chinese medicine group, western medicine group, model group, and set up the control group. Control group and model group did not medicate, only fed distilled water of conventional volume, rats in medication group fed 9.2g medicines / Kg / d or 1.5mg lisinopril / Kg / d medicine group by mice and men dose formula . 6 weeks later , all rats were killed after anesthesia, left the heart myocardium.3. Using Western blot method, real time quantitative PCR, and HE staining and immunohischemistry observed under light microscope to compare the Chinese Medicine group, Western group and blank control group, model group with chronic heart failure cardiac MMP-1, TIMP- 1 and the changes in morphological changes among groups.Results:1. Chronic heart failure animal model group MMP-1 mRNA expression was significantly increased which is 2.671 times of the control group (compared with the control group P <0.01); by drugs intervention MMP-1 mRNA of each treatment group was significantly decreased, Chinese medicine group was most obvious, is 1.420 times the control group (compared with model group P <0.01); Western group is 1.555 times of the control (compared with model group P <0.01), compared with Chinese medicine group P < 0.05, statistically significant.2.Chronic heart failure animal model group, the expression of MMP-1 protein was significantly higher,was 180.232±3.047 (compared with the control group P <0.01); by drug intervention MMP-1 protein expression of each treatment group was significantly decreased, including Western group most obvious, is 83.197±4.919 (compared with model group, P <0.01); Chinese medicine group was 90.387±6.606 (compared with model group, P <0.01), compared with western medicine group medicine group P <0.05, statistically significant.3. Chronic heart failure model group Timp-1 mRNA expression was significantly lower, was 0.743 times of the control group (compared with control group P <0.01); by drug intervention Timp-1 mRNA of each treatment group was increased , Chinese medicine group was most obvious for the control group of 1.846 times (compared with model group, P <0.01, compared with the control group P <0.01); Western group was 1.518 times of the control group (compared with model group, P <0.01, and the control group P <0.01), compared with Chinese medicine group P <0.05, statistically significant.4. Chronic heart failure model group Timp-1 protein expression was significantly reduced, was 73.543±3.140 (compared with the control group P <0.01); by drug intervention the Timp-1 was increased of each treatment groups , Chinese medicine group most obvious was 153.817±12.178 (compared with model group, P <0.01); Western group 142.248±10.862 (compared with model group, P <0.01), compared with Chinese medicine group P <0.05, statistically significant.5. The myocardial cells of blank control group, regular arrangement, stripes clear, normal size , orderly arrangement of myofibrils. Model of cardiac muscle cells formed extensive networks, can not see stripes and disordered myofibrils, a blank area heterochromatin present mass, adjacent cells in the intercalated disk space widened. Chinese cardiac muscle cells arranged in regular, can see stripes, myocardial cells were shrunk to a more solid round, at the edge of cardiac cells, a more orderly arrangement of myofibrils still shows that there are faults and defects and the blank area. Western medicine group myocardial cells arranged in regular , most of the myocardial cells in cardiac cell edge, shape, size normal, more orderly arrangement of myofibrils.6.The average gray of Chronic heart failure model group MMP-1 analyzing by softwarewas 550.14±132.83 ,using immunohistochemistry (compared with the control group P <0.01); Western group impression significantly was 114.72±46.26 (compared with model group, P <0.01); Chinese medicine group was 124.98±30.40 (compared with model group, P <0.01), compared with Western group P >0.05. There is no significant difference among Chinese medicine and Western group.7. The average gray of Chronic heart failure model group Timp-1 analyzing by software was 115.83±43.25, using immunohistochemistry (compared with the control group P <0.01); Western group was 181.16±55.34 (compared with model group, P <0.01); Chinese medicine group was 172.94±48.75 (compared with model group, P <0.01); compared with Western group P >0.05. There is no significant difference among Chinese medicine and Western group. The control group compared with Chinese medicine group and Western group P<0.05,statistically significant.Conclusion:1. Artery ligation combined with hunger and exhaustive style swimming show that this modeling method is feasible with chronic heart failure.by echocardiography and behavioral changes in rats2.After 6 weeks treatment, by using real time quantitative PCR, Western blot, HE staining and immunohischemistry of myocardial tissue in rats , found that benefiting Qi and activating Blood compound prescription plays the relative role of inhibition of the expression on MMP-1 in myocardial tissue model group ; on myocardium in Timp-1 group was significantly higher relative model the role of its expression.3. The data proved that benefiting Qi and activating Blood compound prescription is safe and effective on the treatment of chronic heart failure, relatively more pronounced effect of western medicine Lisinopril.4. TCM Etiology of chronic heart failure was that the heart was inhuried for a long time, resulting in damage to Yin and Yang ,Qi and Blood, all organs dysfunction, the Blood passage blocked, the stopping of water to drink, due to blood stagnation. Pathogenesis of this disease is the key to heart Yang deficiency, benefite Qi and worm Yang, sthengthen spleen and induce water, promote Blood and remove stasis ,the three rules are the most important methods for the treatment of CHF. |
PDF Full Text Request