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Background and Purpose of chronic heart failure (Chronic heart failure, CHF) is currently one of the main cause of health hazards to human health, and studies suggest that ventricular remodeling (Myocardial remodeling) is the basic mechanism of heart failure, myocardial cells and extracellular matrix changes the structural basis of ventricular remodeling, the former including myocardial cell loss and myocyte hypertrophy; latter includes collagen deposition and interstitial fibrosis, myocardial fibrosis (Myocardial fibrosis, MF). MF is a common pathological changes of different causes of cardiac development to a certain stage, significantly increased myocardial interstitial collagen fiber concentration or collagen volume fraction (Collagen volume fraction, CVF) was significantly higher characterized. MF with many clinical events directly related, can lead to heart failure, arrhythmias, cardiac enlargement, sudden death. Recent studies have found that certain cytokines play a key role in the formation of MF. Transformed growth factor β 1 (Transforming growth factorβ 1 , TGF-β 1 ) is the MF, the most important cytokine connective tissue growth factor (Connective tissue growth factor, CTGF) discovered in recent years with organ fibrosis is closely related to the cytokine, TGF-β-mediated 1 downstream signaling proteins as TGF-β < sub> 1 the fibrogenic role, is caused by the MF the important one of the cytokines. Angiotensin II, aldosterone, and transforming growth factor β 1 , endothelin can by upregulating CTGF expression, thus contributing to the formation of the MF. CTGF is now being considered as a new target for anti-MF treatment. Angiotensin II receptor blockers can improve cardiac remodeling, its role has been recognized. But its exact mechanism is not yet fully understood. The purpose of this project is to observe CTGF, TGF-β 1 expression in chronic heart failure in the rat myocardium to explore its exact role in the MF and the concept of MF and fibrosis Chakan candesartan myocardium of CTGF, TGF-β 1 expression, in order to further understand the role of MF in the progression of chronic heart failure. Materials and methods Male Wistar rats adaptive feeding one week the renal the epigastric aortic coarctation making chronic heart failure model, an alternative to the sham group separation of the abdominal aorta suture ligation as controls. After 8 weeks from the performance of rats with heart failure, heart failure model group taking 10 minor symptoms hemodynamic parameters in rats that after reaching the heart failure (LVEDP ≥ 15mmHg), the remaining rats were randomly divided into two groups heart failure group (HF) and drug group (Drug group). Drug group with candesartan 2mg/kg/d gavage, the sham group, HF group with saline. Continue feeding four weeks. Four weeks after the rats with multiple conductive physiological detected hemodynamic parameters observed with Masson staining left ventricular myocardial collagen morphology, image analysis, measurement of collagen volume fraction (CVF) and perivascular collagen area (PVCA), immunohistochemistry assay ventricular TGF-β 1 , CTGF expression. Results 1. Model-making sham rats normal state after 8 weeks, the other two groups of rats apparent heart failure performance; line drugs four weeks after the intervention, the HF group and Drug group, former worsening heart failure, the latter heart failure performed significantly alleviate . 2. Model-making after 12 weeks, three groups of rats systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP) (mmHg): the sham group: 134.38 ± 8.68,95.38 ± 9.24,108.38 ± 8.96; HF group : 119.00 ± 10.30,82.00 ± 8.19,94.33 ± 8.80; Drug group: 115.50 ± 10.49,75.38 ± 9.40,87.42 ± 8.30. HF rats SBP, DBP, and MAP compared with sham group is low, while the latter is higher than the Drug group. HF group and the sham group was statistically significant (P <0.01), compared with the Drug group showed no significant difference (P> 0.05), prompt the HF rats blood pressure levels than sham group was lower, while the HF group Drug group compared to the level of blood pressure change was not statistically significant. 3. The three groups of rats LVEDP (mmHg) after 12 weeks of model making, dp / dtmax (mmHg / s), -dp/dtmax (mmHg / s), respectively: the sham group: 4.63 ± 3.58,5553.50 ± 542.55,3675.50 of ± 410.00; HF group: 21.63 ± 5.71,4172.13 ± 716.55,2831.38 ± 501.50; Drug group: 10.00 ± 3.07,5151.88 ± 376.70,3486.50 ± 349.10. the sham rats LVEDP than HF group was lower, while the latter surpasses Drug group. Among the three groups was statistically significant (P <0.01). dp / dtmax in, -dp/dtmax HF rats compared with sham group (P <0.01) higher than the former and Drug group (P <0.01), compared with sham group, the difference was not statistically significant (P> 0.05 ,), indicating that the the HF rats of heart failure standard the Drug group of heart function improved significantly. 4. Model-making after 12 weeks LVMI%, CVF% PVCA% in the HF group were: 1.87 ± 0.05,3.54 ± 0.66,0.59 ± 0.16; HF group: 3.01 ± 0.12,7.29 ± 1.00,2.03 ± 0.23. Drug group: 2.16 ± 0.11,4.31 ± 0.78,0.89 ± 0.13. Indicators of the HF group was significantly higher than the sham group (P <0.01); compared with the HF group Drug group was significantly lower (P <0.01). HF myocardium matter fibrous tissue deposition more, while the the Drug group of myocardial fibrosis to a lesser extent. 5. Immunohistochemical detection of CTGF in myocardial vascular smooth muscle and myocardial interstitial Jieyou expression, TGF-β 1 expression in myocardial interstitial. CTGF, TGF-β 1 in the three groups of rats myocardial expression values ??were (mean gray value): the sham group: 106.25 ± 12.45,93.38 ± 9.00; HF group: 131.71 ± 10.78,161.00 ± 13.63; Drug group: 117.33 ± 11.61,116.88 ± 12.24. CTGF in myocardium of sham rats around the vascular smooth muscle weakly positive expression in the HF group was strongly positive expression of myocardial mass also express, Drug myocardium decreased expression of the HF group and sham group (P <0.01), Drug group and HF group (P <0.01), the sham group and Drug group: (P <0.01). TGF-β 1 myocardial interstitial expression compared to the HF group, sham group and the of Drug group of rats any two groups the difference was statistically significant (P <0.01). These data show that after four weeks of candesartan treatment can reduce but not completely blocked CTGF, TGF-β 1 expression. Conclusion 1. Myocardial fibrosis may be pressure overload in the pathogenesis of chronic heart failure; 2. CTGF, TGF-β 1 involved in the onset of myocardial fibrosis in pressure overload in rats with heart failure; 3. Candesartan reverse ventricular remodeling may be related to the decrease of CTGF, TGF-β 1 expression; 4. Selectively reduce CTGF expression may be a new method for the future treatment of myocardial fibrosis.
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