| Purpose：Chronic heart failure is a complex process of development, and remodeling isthe key to this pathological process, subject to the regulation of a varietyof factors, including matrix metalloproteinases (MMP-2) and tissue inhibitor(TIMP-2) is the ventricular re-structure during one of the important regulatoryfactors. The experiment is through the establishment of rat model of chronicheart failure after myocardial infarction, to observe the supplementing qi,activating blood circulation, and promoting urination in three differentChinese herbal compound in chronic heart failure in rat heart tissue of MMP-2and TIMP-2expression, and to study the three kinds of traditional Chinesemedicine treatment of chronic heart failure, the best combination of itsmechanism, clinical use of Chinese medicine to provide a scientific basis andtheoretical guidance.Material and method：1.Choose200to250grams body weight, general health level12-week-old maleWistar rats were100, adaptive feeding week after coronary artery ligation andto reduce hunger with food, method of exhaustive swimming style after myocardialinfarction in rats caused by chronic heart failure model. By Dopplerechocardiography of left ventricular ejection fraction EF≤40%, while thosein poor mental state in rats to determine the success of modeling as the observedobject.2. The successful model rats were randomly divided into groups of supplementingqi, activating blood circulation, supplementing qi and activating bloodcirculation, and replenishing qi activating blood and promoting urination,western medicine group, model group, and for an additional sham-operated group served as controls. Each group were fed with the corresponding traditionalChinese medicine Chinese medicine, Western medicine group fed with lisinopril,administered by one mouse dose volume conversion, model group and sham operationgroup fed with equal volume of saline, were fed for6weeks.3. After6weeks, measured by color Doppler ultrasound machine cardiac function,and the rats of the left ventricular ejection fraction (LVEF), fractionalshortening (FS) of the comparison.4. The rats were sacrificed, the heart weighed out, and compare its weight.5. Whichever part of the left ventricular myocardium by immunohistochemistry、Real-time fluorescent quantitative PCR method and HE staining of myocardialtissue were measured in rats MMP-2, TIMP-2expression and morphological changes.Results：1On rat cardiac function:Compared with the sham group, model group, left ventricular ejection fraction (LVEF%) was significantly lower (P <0.01); compared with model group, the rats were given medicines group for LVEF%significantly higher (P <0.01); compared with western medicine group, activating blood circulationgroup, supplementing qi and activating blood circulation group, and replenishing qi activating blood and promoting urination group rats LVEF%was notstatistically significant,(P>0.05); between groups of traditional Chinesemedicine, replenishing qi activating blood and promoting urination grouprats LVEF%was significantly higher than the supplementing qi group,activating blood circulation group, supplementing qi and activating blood circulation group,(P <0.05); which supplementing qi and activating blood circulation group was better than supplementing qi group (P <0.05).Compared with the sham group, model group, fractional shortening (FS%)was significantly lower (P <0.01); compared with model group, the rats given medicines group FS%was increased (P <0.01); supplementing qi and activating blood circulation group rats FS%compared with the western medicine g roup (P>0.05); between groups of traditional Chinese medicine, replenishing qi activating blood and promoting urination group FS%was significantlyhigher than supplementing qi group, activating blood circulation group, supplementing qi and activating blood circulation group, both P <0.01; which supplementing qi and activating blood circulation group was better than supplementing qi group (P <0.01).2. Of the rat heart weight and heart weight ratio of：Compared with the sham group, model group, heart weight increased significantly (P <0.01); compared with model group, supplementing qi and activating blood circulation group, replenishing qi activating blood and promoting urination group, western medicine group were the heart weight was significantly lower (P <0.01); the given medicines between the groups, compared with western medicine group, supplementing qi group, supplementing qiand activating blood circulation group, replenishing qi activating blood and promoting urination group in the heart weight of rats no significant difference between (P>0.05); which, replenishing qi activating blood and promoting urination group and the supplementing qi and activating blood circulation group heart weight compared with supplementing qi group, activatingblood circulation group was significantly lower (P <0.05).Compared with the sham group, model group, heart weight ratio was significantly increased (P <0.01); compared with model group, the rats were given medicines group for heart weight ratio was significantly lower (P <0.01); the given medicines between the groups, compared with western medicine group, supplementing qi and activating blood circulation group, replenishing qi activating blood and promoting urination group rats the heart weight ratio between the difference was not statistically significant (P>0.05); where replenishing qi activating blood and promoting urination group and the supplementing qi and activating blood circulation group heart weightratio than the supplementing qi group, activating blood circulation groupwas significantly lower (P <0.05). 3. Determined by immunohistochemical staining of myocardial tissue of ratsMMP-2, TIMP-2protein expression：Compared with the sham group, model group, myocardial tissue expression of MMP-2was significantly higher (P <0.01); the given medicines betweengroups: protein expression trends from the point of view, replenishing qiactivating blood and promoting urination group of MMP-2expression was weaker than supplementing qi and activating blood circulation group; supplementing qi and activating blood circulation group of MMP-2expression was weaker than activating blood circulation group and the supplementing qi group,then the replenishing qi activating blood and promoting urination group、supplementing qi and activating blood circulation group compared with western medicine group，the MMP-2expression differences were not statistically significance (P>0.05).Compared with the sham group, model group, myocardial tissue of TIMP-2expression was significantly lower (P <0.01); the given medicines betweengroups: protein expression trends from the point of view, replenishing qi activating blood and promoting urination group of TIMP-2expression was stronger than supplementing qi and activating blood circulation group, supplementing qi and activating blood circulation group of TIMP-2expression wasstronger than activating blood circulation group and the supplementing qigroup, then the replenishing qi activating blood and promoting urination group、supplementing qi and activating blood circulation group compared withwestern medicine group，the TIMP-2expression differences were not statistically significance (P>0.05).4. Real-time fluorescent quantitative PCR method for the determination of the myocardial tissue of MMP-2mRNA and TIMP-2mRNA expressionCompared with the sham operation group, model group, myocardial tissueexpression of MMP-2mRNA was significantly higher (P <0.01). Between each dosing group: replenishing qi activating blood and promoting urinationgroup of MMP-2mRNA expression was weaker than the supplementing qi group ，activating blood circulation group and the supplementing qi and activating blood circulation group (P <0.01).Compared with the sham operation group, model group, myocardial tissueof TIMP-2mRNA expression was significantly reduced (P <0.01). Among thedosing groups: replenishing qi activating blood and promoting urination group of TIMP-2mRNA expression was stronger than the supplementing qi group，activating blood circulation group and the supplementing qi and activating blood circulation group (P <0.01).5.HE staining of myocardial tissue were measured in rats morphological changes：Sham group: Myocardial cells arranged in compact regular, intercalateddisc, clear stripes, horizontal longitudinal section observation, the same morphology, myocardial cell nuclei in the myocardial cell edge, shape,size, normal muscle fiber (or fibers) arranged in order, fracture and defect-free, blank area.Model group: Myocardial cells interwoven into a network, do not see the stripes, myocardial cell nuclei, myocardial fibers were irregularly arranged, breakage and loss of myocardial cell shrinkage, a blank area, heterochromatin present mass, the adjacent cells, intercalated disc space widened.Western medicine group：Myocardial cells arranged in a more structured,visible stripes and most of the cell nucleus, size, normal myocardium, edgein myocardial cells, and muscle fibers arranged in a more orderly, still visible faults and defects, and white space non-uniform coloring.Replenishing qi activating blood and promoting urination group: Myocardial cells arranged in a more structured, visible stripes and intercalated disc clear, myocardial nuclear pyknosis round, located in edge of myocardialcells, muscle fibers arranged in a more orderly, and white space visible faults and defects.Supplementing qi and activating blood circulation group: Myocardial cel ls arranged in a more structured, visible stripes and visible of myocardialnuclear pyknosis round, located in edge of myocardial cells, muscle fibersarranged in a more orderly, and white space visible faults and defects.Activating blood circulation group: Myocardial cells compared with model group has improved, can not see the stripes, myocardial cell nuclei, myocardial fibers were irregularly arranged, breakage and loss of myocardialcell nuclei shrinkage, there is still a blank area, still visible heterochromatin lumps, showing that there defects and faults and uneven coloringthe blank area.Supplementing qi group: Compared with model groups had improved, invisible stripes and myocardial nuclei, fibers arranged in a more structured, breakage and loss, of myocardial nuclear pyknosis, there are still gaps, still see heterochromatin is massive, and intercalated disc gap widening in adjacent cells.Conclusion：1. To coronary artery ligation and with hunger, less food, exhaustive style swimming method, by echocardiography testing and assessment of mental state in rats, that this law causes of chronic heart failure after myocardial infarction in rat models feasible.2. After6weeks of drug treatment, by measuring the weight of the rat heart, heart to body weight ratio and cardiac function，and determined by immunohistochemistry and Real-time fluorescent quantitative PCR method，HE staining method for the determination of myocardial tissue found that each treatment group can significantly improve left ventricular remodeling in rats with chronic heart failure,reduce the myocardial tissue of MMP-2expression increase of TIMP-2expression, improve the shape of the myocardial tissue, play a role in promoting the improvement of cardiac function, the trendof the expression from high to low are: replenishing qi activating blood and promoting urination group, supplementing qi and activating blood circul ation group, activating blood circulation group, supplementing qi group.3. By the above data, describes the supplementing Qi and activating blood circulation and inducing diuresis Chinese herbs combined with treatment of chronic heart failure is a proven method. Herbs on the improvement of left ventricular remodeling and cardiac function may work by affecting the balance of MMP-2/TIMP-2. Which supplementing qi and activating blood circulationgroup, replenishing qi activating blood and promoting urination group compared the efficacy of supplementing qi group, activating blood circulationgroup was significantly,and the effect of no less than Western medicine(lisinopril). |
PDF Full Text Request