| Objective: This study aims at assessing whether the progression of rats heart failure(HF) and the myocardial remodeling recovery attenuated after the rat models transfected with recombinant adenovirus vector-mediated Klotho gene. However, the role of Klotho gene in heart failure is complex and remains controversial. We approach to the possible mechanisms how Klotho gene repair the myocardial injury. Methods : Rats were divided into 5 groups by table of exponential random numbers: normal control group, HF group, saline-control HF group, recombinant adenovirus vector transfection group(AD.Klotho group, 2×1010 pfu, 0.5 ml/rat), p DC316-CMV-EGFP-Klotho transfection group(AD.Klotho group, n=6 each). Left ventricular ejection fraction(LVEF) was obtained by echocardiography, hemodynamic parameters obtained by multi-channel physiological recorder, myocardial tissue underwent pathohistological examination. Additionally, the green fluorescin expression was observed on frozen heart section. Myocardial fibrosis correlated gene expression including Klotho gene, collagen Ⅰa1 and Ⅲa1was detected by Real Time-PCR. Moreover, plasma levels of B-type natriuetic peptide(BNP) were measured with ELISA. Results: In contrast to HF group of saline control, the progression of myocardial fibrosis attenuated as well as myocardial remodeling in the pathohistology section. We could also see the green fluorescin distributed around in myocardial tissues of AD. Klotho group. HF rats with down-regulated Klotho(P<0.05) and up-regulated Collagen Ⅰ and Ⅲ(P<0.05) were remarkably detectable in myocardial tissues, while Klotho up-regulated after transfecting the virus(P<0.05). Group of Heart Failure has low LVEF(42.27±3.22%) than Control(72.13±2.97%) in echocardiography,(P<0.01). There are statistical differences of Heart Rate in Control(364.33 ± 6.44)and AD.Klotho(348.50±1.87) to F-Model(341.83±8.42), F-NS(344.67±7.42), and AD.EGFP(340.83±11.16),(P<0.05)。As well as in LVSP, Control(145.00±2.53)and AD.Klotho(122.83±4.71) to F-Model(96.83±3.19), F-NS(96.33±2.50), and AD.EGFP(95.83 ± 3.92),( P<0.01). Similarly, for LVEP, Control(13.83±2.48)and AD.Klotho(19.83±2.56) to F-Model(24.33±1.97), F-NS(23.67±3.08), and AD.EGFP(25.17±2.04),(P<0.01).Except that, we also found the statistical differences in ± dp/dtmax, Control(5988.33 ±94.28)vs(4139.50 ± 158.83)and AD.Klotho(3108.33 ± 139.89) vs(2504.83 ±157.96) to F-Model(2020.83±103.19) vs(1658.17±146.63), F-NS(2018.67±124.48) vs(1664.83±131.77), and AD.EGFP(89.05±36.35) vs(1693.50±117.28),(P<0.05).There are statistical differences of BNP levels in plasma between control rats versus HF rats(P<0.01) similar to Klotho.null versus AD.Klotho(P<0.05). Conclusions: Models of rat heart failure can be constructed effectively by isoproterenol-induced intraperitoneal injection. Klotho gene could attenuate cardiomyocytes hypertrophy and restrain collagens hyperplasy in the progression of myocardial fibrosis. Down-regulated Klotho gene that acting on correlated pathway maybe one of mechanisms to promote cardiomyocytes apoptosis even induced myocardial fibrosis as well as myocardial remodeling. |
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