| Background and ObjectiveMyocardial hypertrophy is the adaptive change to various stimulations.The pathological changes include cardiacmyocyte hypertrophy,the proliferation and fibrosis of cardiac interstitial fibroblasts. In clinical practice,a lot of diseases could lead to myocardial hypertrophy,such as hypertension, coronary heart disease,valvular heart disease,congenital heart disease,and so on.Myocardial hypertrophy is an independent risk factor of heart failure, arrhythmia,sudden death and other cardiovascular diseases. In the field of cardiovascular, it is urgent to explore the mechanism of myocardial hypertrophy and correlative intervention measures about drugs.Myocardial hypertrophy involves in multiple signal pathways.By interacting with its receptors and then initinting the intracellular messenger transduction,some chemical signals can activate the corresponding protein kinase,such as Ca+2, mitogen-activated protein kinases(MAPKs),protein kinase C,Janus kinase, phosphoinositide 3 kinase(PI3K),and so on.The mechanical signal can stimulate the release of angiotensin Ⅱ, norepinephrine and other growth factors, andfurtherly activate the stress sensors,which could transmit signals to the nucleus.Various pathways cross each other and form a complicated network.Now more and more studies have shown that inflammatory or autoimmune response participates in the pathophysiological process of myocardial hypertrophy.ST2 is a member of IL-1 receptor family,and its essence is a kind of protein.Under the condition of pressure overload or hemodynamic changes,ST2 mainly expresses by myocardial cells and fibroblasts.By alternative splicing,ST2 gene encodes at least three isoforms of ST2 proteins,including soluble ST2(s ST2),transmembrane ST2(ST2L) and variant ST2(ST2 V). In the heart,ST2 L and s ST2 are the main expression forms. As the receptor of IL-33,ST2 L has been proved playing the effect of protection in myocardial infarction, heart transplantation and heart failure.Currently,some researches have found that aldosterone receptor antagonist can adjust the intermediate metabolites of IL-33/ST2 singal pathway in myocardial cells,which can strengthen the combination of IL-33 and ST2 L,and then reduce the s ST2 concentration in serum.Finally,it can play a role of resisting myocardial remodeling in myocardial infarction and heart failure.Objective This study by subcutaneous injection of isopropyl adrenaline making myocardial hypertrophy model of rat,intends to observe the concentration change of s ST2 in myocardial hypertrophy tissue,to explore the effect of spironolactone on s ST2 of IL-33 / ST2 signal pathway and the mechanism of resisting myocardial hypertrophy.Methods The thirty healthy male SD rats were fed for a week.According to the method of stochastic digital,these rats were randomly divided into model group,drug intervention group and control group(n=10, in each group).Model group and drug intervention group rats were subcutaneously injected the drug of isopropyl epinephrine(isoproternnol,ISO)2.5 mg/(kg, d);Control group rats were subcutaneously injected with the equal dose of normal saline, continuously for 14 d.From the day of mading the model of Myocardial hypertrophy, the spironolactones were dissolved in 2 ml water to lavage the rats of drug intervention group by the dose of 20 mg/(kg.d).In the model group and control group rats were lavaged with the same dose of physiological saline, last for 8 weeks. After 8 weeks,three groups of rats were measured the quality of body, heart and left ventricular.By calculating the heart quality index(HM/BM), left ventricular mass index(LVM/BM),the degree of myocardial hypertrophy can been understood.At the same time, myocardial tissue slice were prepared for HE staining to observe the myocardial tissue form and the size of myocardial cell diameter;in addition,the expression of s ST2 m RNA and s ST2 protein in left ventricular tissues were analyzed by reverse transcription polymerase chain reaction(RT-PCR) and immunohistochemistry.Results1 Cardiac mass index and left ventricular mass indexThe results of Cardiac mass index(HW/BW) as follows: control group < drug intervention group < model group(2.47+0.07mg/g vs 2.79+0.07 mg/g vs 3.39+0.11mg/g,P < 0.05),the difference of three groups was significant.The results of left ventricular mass index(LVM/BM) as follows: control group < drug intervention group < model group(1.78+0.07 mg/g vs 1.92+0.10 mg/g vs 2.34+0.11 mg/g, P <0.05), the difference of three groups was significant.2 Myocardial tissue pathological morphology changes and the diameters of myocardial cellsIn control group, the myocardial cells were normal and arranged appropriately;In Model group,the myocyte were hypertrophy, disordered, and the hyperplasia of fibrous tissue was visible;Compared with model group,the myocardial cells in drug intervention group were a litter tider;Myocardial cell diameter: control group < drug intervention group < model group(,P < 0.05), the difference of three groups was significant.3 ImmunohistochemicalAfter immunohistochemical staining,s ST2 displays tan particles in myocardial cells normally.But in the control group,only saw a small amount of brown granules,a weak positive expression;In model group, a large number of tan granules can be seen in the myocardial cells, a strong positive expression;In intervention group,the tan particles were less than model group,a positive expression, the difference of three groups was significant. The comparison of average optical density value in three groups of rats:control group < drug intervention group < model group(0.03±0.02 vs0.15±0.01 vs 0.28±0.01,P < 0.05), the difference of three groups was significant.4 s ST2 mRNA content in hypertrophic myocardium of ratsRT-PCR method was used to measure the relative content of s ST2 m RNA in myocardial cells of three groups of rats : control group < drug intervention group <model group(0.15±0.01 vs 0.18±0.01 vs 0.50±0.04,P < 0.05), the difference of three groups was significant.Conclusions1.The expression of s ST2 in the tissue of myocardial hypertrophy is high,showing that s ST2 can promote the formation of myocardial hypertrophy.2. After the intervention of aldosterone receptor antagonist spironolactone, s ST2 expression in the tissue of myocardial hypertrophy is lower than the model group, and the degree of myocardial hypertrophy is lessen than the model group.The results indicates that spironolactone may enhance the role of against myocardial hypertrophy in IL-33/ST2 L pathways by reducing the s ST2 concentration. |
PDF Full Text Request