| Background and ObjectiveHypertrophic cardiomyopathy in cardiac hypertrophy is characterized by a type of heart disease. Myocardial hypertrophy is a non-specific adaptation of myocardial cells to a variety of injuries, mainly to changes in myocardial remodeling, myocardial hypertrophy and myocardial interstitial component. Sudden death is a major risk, general adult10-year survival rate of80%, children50%,4%to6%of middle-aged mortality in high-risk patients. Its pathogenesis has still not very clear.It has been reported myocardial extracellular matrix myocardial collagen abnormalities in myocardial remodeling mechanisms important role in cardiac myocyte hypertrophy and collagen deposition is not synchronized development is one of the main reasons causing cardiac hypertrophy. Extracellular matrix (extracellular matrixc, ECM), is synthesized by the animal cells and secreted into the extracellular, the distribution of macromolecules between the cell surface or cell, including a fiber component (such as collagen and elastin), fibronectin (such as fiber even proteins, etc.) and filled molecules (usually glycosaminoglycan).Myocardial hypertrophy (cardiac hypertrophy) myocardial hypertrophy of cardiovascular disease is a common pathological process. The occurrence of the structure is based largely on myocardial cell increases and fibrosis. Seen in high blood pressure, pulmonary hypertension, heart valve disease, and other common congenital heart disease of cardiovascular disease. The process involves the myocardial cell hypertrophy and stromal elements change, also called myocardial reconstruction. Myocardial reconstruction eventually lead to coronary blood reserves reduce, increase myocardial ischemia, and lead to heart failure, arrhythmia, sudden death, etc. At present many studies show that the extracellular matrix (extracellular matrix, ECM) especially type I and type III collagen fiber of abnormal changes, myocardial reconstruction in plays an important role. The reconstruction of the extracellular matrix, especially the collagen deposition and myocardial myocardial cell hypertrophy not synchronous development is prompted by myocardial hypertrophy compensatory decompensated change to one of the main reasons.Matrix metalloproteinase (matrix metalloproteinase; MMP) by the hydrolysis of extracellular matrix protein cleaving enzyme, mainly constituted by the collagenase and elastase. The same kind of matrix metalloproteinase-degradable more extracellular matrix components, and there is a component of the extracellular matrix by a variety of matrix metalloproteinases can be degraded by degradation of the enzyme but with different efficient and differences. Matrix metalloproteinase expression and activity increased, normal myocardium can lead to excessive degradation of collagen, was the lack of connection structure replaced by fibrous stroma, the heart tissue remodeling, resulting in deterioration of heart function. MMP1biodegradable denatured collagen. MMP3major role in type Ⅲ, Ⅳ collagen and gelatin. A lot of studies have demonstrated the generation of myocardial remodeling and RAAS system dependent. RAAS is the role of angiotensinogen in the renin angiotensin peptides formed under ten Ⅰ, angiotensin Ⅰ under the action of angiotensin converting enzyme octapeptide Angiotensin Ⅱ, and then acting on the angiotensin Ⅱ its specific receptor, causing oxidative stress, vasoconstriction, aldosterone secretion, causing a series of pathological cardiac remodeling effect. Olmesartan belongs to class of ARB drugs, which can be completely blocked angiotensin Ⅱ binding to its receptor, thereby inhibiting myocardial remodeling.This experiment is to establish the myocardial hypertrophy in the rat model and ogilvy, sand intervention, observation rats in the MMP3and myocardial MMP1expression, sand for ogilvy, improve cardiac muscle to provide the evidence that the reconstruction.MethodsRandom selection of Wistar rat only30, divided into the control group, model group, intervention group every10. The control group back subcutaneous injection physiological saline, dosage1ml/(kg. d.), twice a day for10days saline irrigation stomach1ml/d. Model group, the intervention group back subcutaneous injection isoproterenol, dosage3mg/(kg.d),2times a day, for10days, and the control group and the model group every day saline irrigation stomach1ml/d, intervention group every day, sand filling ogilvy&mather stomach once, dosage0.5mg/(kg. d), for10days.Three groups of animal experiment end immediately weighing, again will each rat with10%hydration chlorine aldehyde3ml/kg intraperitoneal injection of anesthesia, open chest, take heart, says the wet weight and take heart left ventricular wet weight. Part of the myocardial specimens preserved in liquid nitrogen, used to extract RNA in Real-time PCR. The other part of in 100g/L polyphosphate fixed in formaldehyde, the conventional paraffin slice (5μm).Results1Determination of cardiac mass index and left ventricular mass index.①Cardiac mass index (HW/BW):Model group than in the intervention group than the control group,(2.77±0.09mg/g vs2.54±0.09mg/g vs2.19±0.03mg/g, P<0.05).②Left ventricular mass index (LVW/BW):Model group tha n in the intervention group than the control group,(2.47±0.02mg/g vs2.21±0.02mg/g vs1.78±0.01mg/g, P<0.05)2HE stainingControl rat myocardial cells arranged in neat rows, and myocardial structu re is clear and complete, no morphological abnormalities, and no morphologica1changes in the nucleus, cytoplasm was pink and more uniform staining. Com pared with the control group, the model group, the myocardial cells are hypert rophy, interstitial cells visible apparent proliferation of fibrous connective tissue, and myocardial gap widened significantly. The intervention group compared w ith the model group, the visible myocardial cells slightly increased cell-to-cell arrangement is acceptable, also myocardial tissue fibrous hyperplasia, but less r elative to the model group.3Reverse transcriptase polymerase chain reaction (RT-PCR)Among the three groups of MMP-1mRNA relative content compared with the model group than in the intervention group than the control group.(0.626±0.037vs0.313±0.018vs0.107±0.009,P<0.05). MMP-3mRNA relative c ontent among the three groups compared with the model group than in the int ervention group than the control group.(0.405±0.024vs0.196±0.013vs0.084±0.007, P<0.05)4immunohistochemistry MMP-1positive area in the three groups in the average integrated opti cal density compared with the model group was the highest, followed by the i ntervention group, the control group.(162.81±3.97vs131.89±2.51vs110.28±2.53,P<0.05). MMP-3positive area in the three groups in the average integ rated optical density compared with the model group was the highest, followed by the intervention group, the control group.(149.42±8.86vs127.47±2.65v s115.12±6.01,P<0.05).Conclusions1. Model of cardiac hypertrophy in rats is established by subcutaneous inje ction of isoproterenol for10days.2. Hypertrophied myocardial tissue MMP-1and MMP-3expression increase d, suggesting that MMP-1and MMP-3involved in cardiac hypertrophy induce d by isopropyl adrenal occurred.3. The olmesartan intervention MMP-1and MMP-3expression in the myoc ardial tissue of rats were lower than the model group, suggesting that the mec hanism may be related to the inhibition of MMP-1and the expression of MM P-3expression telmisartan cardiac hypertrophy. |
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