| Background and ObjectiveHypertension is one of the most common etiological factor of heart failure, long-term blood pressure could lead to as the main features of myocardial hypertrophy of heart attack. Myocardical hypertrophy is a chronic compensatory reaction of the heart long-term overloading and excessive activation of the neuroendocrine system; as hypertension, coronary heart disease (myocardial infarction), heart valve disease, congenital heart disease and other cardiovascular disease common pathological process and basic responses. Hypertension could be leads to myocardial hypertrophy is an important part of the process of development of heart failure, its mechanisms are:hypertrophic factor stimuliâ†'cellular signal transductionâ†'gene transcriptionâ†'myocardial hypertrophyâ†'heart failure, therefore blocking signaling pathway can reduce heart failure incidence, thus reducing risk of sudden death and mortality. Therefore, the study of myocardial hypertrophy signaling pathway has clinical significance.During the past decades, lots of evidence examined that mitogen activated protein kinase, namely, MAPK, has been confirmed closely related to hypertension induced myocardial hypertrophy in signal transduction, MAPK would become the new therapeutic targets of vascular remodeling in hypertension. GATA families, which is named because of it having common zinc finger DNA binding domain, and it's could identify the "GATA" DNA sequence.GATA-4,5,6 are closely related to heart development,cardiac growth and differentiation, and it's directly regulater in specific genes of the heart hypertrophy process.GATA4 is the most important one in cardiac hypertrophy process. Recently, a mass of studies have shown that GATA4 transcriptional activation has great significance for the prevention of cardiac hypertrophy development.P38 mitogen-activated protein kinase is a intersection of cell signal transduction. recently years,a large number of studies have shown:P38 MAPK signaling pathway is not only involved in atherosclerosis, myocardial ischemia and other pathological processes, but also can be achieved through a variety of ways in promoting the cellular mechanisms of cardiac hypertrophy pathways.Here, we made used of cardiac hypertrophy model by subcutaneous isoproteren-ol of rats.Observation P38 mitogen activeted protein kinase and GATA4 relationsh-ips, to explore the GATA4 pathway in cardiac hypertrophy,to apporch the role as well as the mechanism of P38MAKP and GATA4 in this model, and to investigate the effect of telmisartan. Apporaching the possible reversal of myocardial remodeling mechanisms of drug effects for the genetic level, to provide clinical drugs therapy of theorety.MethodsHealthy adult female SD rats were 45, randomly divided into 3 groups, n= 15: control group, model group and drug treatment group.â‘ control groups: subcutaneous injection of saline and gavaged isodose saline;â‘¡model group: subcutaneous injection of isoproterenol (ISO):3mg/kg/d and gavaged isodose saline;â‘¢drug intervention groups:subcutaneous injection of isoproterenol (ISO) 3mg/kg/d and gavaged telmisartan (8mg/kg/d); continuously fed for 10 days.After 10 days the application of multi-channel biological signal analysis the system of hemodynamics parameters, calculated the parameters of left ventricular mass.while observed morphous of the left ventricular by HE staining,immunohistochemistry, and P38MAPK GATA4 expression was observed, with reversal recorded polymerase chain reaction (RT-PCR) to monitor the mRNA levels P38MAKP and GATA4. Results1. The changes of hemodynamic parameters1.Systolic blood pressure (SBP):ten days of continuous subcutaneous isoproterenol (ISO) SBP was obviously higher than that of model group (147.67±13.56mmHg vs 124.07±9.70mmHg, P<0.05), drugs SBP was in the middle of three groups (140.50±9.14mmHg vs 124.07±9.70mmHg; 140.50±9.14mmHg vs 147.67±13.56mmHg; P<0.05),there were significant difference among three groups;2.Left ventricular end-diastolic pressure (LVEDP), Model group was obviously higher than that of control group (11.13±2.45mmHg vs 5.86±1.23mmHg; P<0.05), LVEDP of Drug group was between other two groups (9.43±1.83mmHg vs 5.86±1.23mmHg; 9.43±1.83mmHg vs 11.13±2.45mmHg; P<0.05).2. The changes of LVMILVMI of Model group was obviously higher than that of control group (2.641±0.1023mg/g vs 2.226±0.0778mg/g; P<0.05), LVMI of Drug group was between other two groups (2.343±0.0587mg/g vs 2.641±0.1023mg/g; 2.343±0.0587mg/ g vs 2.226±0.0778mg/g; P<0.05)3. the observation of HE stainingMyocardial structure in control rats clear, neat, no abnormal morphology; model group, myocardial hypertrophy, myocardial relatively disordered cell arrangement, the texture was thicker filaments, visible myocardial interstitial fibrosis; drug group the intervention group myocardial damage in model group, but the abnormal cell morphology were seen.4. the result of RT-PCRISO model group left ventricular myocardial tissue P38MAKP mRNA significa-ntly higher relative content of the drug group between model group and control group, there are significant differences between the groups (1.176±0.127 vs 0.324±0.021 vs 0.513±0.069, P<0.05); GATA4mRNA relative content of the data, the model group were lower than the control group, intervention group living in the model group and control group, each group a statistically significant difference (0.189±0.022 vs 0.854±0.087 vs 0.615±0.058; P<0.05).5. The results of immunohistochemistry staining Model group, left ventricular muscle P38MAKP ISO average integrated optical density was significantly higher in model group and drug group in the control group, there are significant differences between the groups (686.111±435.54 vs 218.028±101.85 vs 319.25±130.04; P<0.05); GATA4mRNA relative content of the data, the model group were lower than the control group, intervention group living in the model group and control group, each group a statistically significant difference (0.052±0.013 VS 0.138±0.035 vs 0.083±0.024; P<0.05).Conclusion1. After subcutaneous injection 10 days isoproterenol method can be success-fully established cardiac hypertrophy model.2. P38MAPK and GATA4 participate in cardiac hypertrophy process of induced by isoproterenol.P38MAPK expression upregulation facilitate cardiac hypertrophy process, and GATA4 protein decreases could be negative regulation to myocardial hypertrophy. P38MAPK could regulating GATA4 protein levels to enhance of myoc-ardial hypertrohy.3. Afte Telmisartan interferencing rats P38MAPK higher control group levels, lower model group; GATA4 is lower control group, higher the model group, indicating that Telmisartan may be by passage P38MAPK/GATA4 pathway at the molecular level inhibition partly myocaldial hypertrophy. |
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