| Backgrounds and objectives:Our previous study have found the association of left ventricular dysfunction with myocardial fibrosis and multidimensional deformation in spontaneously hypertensive rats(SHR), but the relationship between left ventricular function and cardiomyocyte apoptosis is not clearly understood. In this part, we observe the distribution of cardiomyocyte apoptosis in SHR and its relationship with both left ventricular function and apoptosis-associated protein(Bcl-2, Bax, Fas), which is aim to explore the importance of cardiomyocyte apoptosis in the development of cardic dysfunction in hypertension and how the apoptosis-associated protein regulate the cardiomyocyte apoptosis.Methods:SHR and WKY rats were randomly divided into several groups, 5-6 for each group, experiments were performed at different weeks(12, 28, 45, 66, 84, 102w).(1)Echocardiographic measurements included LVMI, LVEF and FS.(2)Invasive parameters included LVEDP and LV±dp/dtmax.(3)TUNEL assay: cardiomyocyte apoptosis index(APOI) in subendocardial and subepicardial myocardium. Masson staining: myocardial collagen volume fraction(CVF) in subendocardial and subepicardial myocardium, perivascular collagen area(PVCA).(4) Western blot analysis included Bax, Bcl-2 and Fas.Results:1. Echocardiogram indexes: The blood pressure of SHR is higher than WKY group(p<0.05). LVMI increased with aging in both SHR and WKY, and SHR were different from WKY group from 45 wk(p<0.05); LVEF and FS decreased at 84 wk in SHR, which were different from WKY group(p<0.05).2. Cardiac catheterization index: In SHR, LVEDP increased until 45 wk and prominently higher than the WKY rats(p<0.05), whereas LV±dp/dtmax increased significantly at 28 wk(p<0.05), and significantly decreased at 84 wk, which were different from WKY group(p<0.05).3. Histologic index: CVF, PVCA in SHR increased with age, CVF in subendocardial myocardium significantly increased at the age of 66 wk(p<0.05), PVCA also increased at 66 wk(p<0.05); Whereas, subepicardial myocardium of CVF and PVCA significantly increasement appeared at 84 wk in SHR(p<0.05). Cardiomyocyte APOI in SHR increased with age, APOI in subendocardial myocardium significantly increased at the age of 66 wk(p<0.05); Whereas, subepicardial myocardium of APOI significantly increasement appeared at 84 wk in SHR(p < 0.05).4. Western blot analysis: there were no difference in the expression of Bcl-2 between SHR and WKYs at 12 wk, whereas the expression in SHR at 66 wk were lower than 12 wk(p<0.05). In 102 wk, the expression in SHR were continue decreased(p<0.05). There were no difference between the expression of Bax, Fas and Bax/Bcl-2 at 12 wk between SHR and WKYs, whereas the expression of SHR at 66 wk were more than 12 wk(p<0.05). In 102 wk, the expression of SHR were continue increased(p<0.05).5. Linear correlation analysis: myocardial APOI and LVMI、CVF、PVCA showed an obvious correlation(r=0.83, 0.89, 0.72, p=0.00); Myocardial APOI showed a negatively correlation(r=-0.81, p=0.00) with LVEF in 66-102 wks. Fas,Bax/Bcl-2 showed an obvious correlation with myocardial APOI(r=0.81, 0.79, p=0.00).Conclusion:1. The myocardial apoptosis were increased gradually with aging and increased prominently when SHRs developed heart failure, indicating its association with the left ventricular remodeling, myocardial fibrosis, as well as the impaired cardiac function.2. Fas, Bax/Bcl-2 showed an obvious correlation with myocardial apoptosis, indicating these apoptosis-associated protein may regulate the myocardial apoptosis of SHRs. |
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