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Improvement of Heart Function in Postinfarction Heart Failure Swine Models after Hepatocyte Growth Factor Gene Transfer: Comparison of Low-, Medium- and High-dose Groups

Author: ZhangSheng
Tutor: YangZhiJian
School: Nanjing Medical University
Course: Department of Cardiology
Keywords: Hepatocyte growth factor Different doses Cardiac function Apoptosis Vascular regeneration
CLC: R542.22
Type: Master's thesis
Year: 2008
Downloads: 48
Quote: 0
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Abstract


Objective: To study by coronary transfected with different doses of adenovirus (adenovirus, Ad 5 ) carry hepatocyte growth factor (hepatocyte growth factor HGF) on the improvement of heart function after swine myocardial infarction The dose-effect relationship. Methods: 24 miniature pigs were randomly divided into a control group (nu11-Ad 5 -HGF small dose group (1 × 10 9 1 ml of), Ad . pfu / ml, 1ml), Ad 5 -HGF middle dose group (5 × 10 9 pfu / ml, 1ml), Ad 5 < / sub>-HGF large dose group (1 × 10 10 pfu / ml, 1 ml) of each group by ligating left anterior descending artery remote production model of myocardial infarction four weeks after treatment the the group right coronary artery in coronary angiography inject the appropriate dose of Ad 5 -HGF (1 ml), control group injected nu11-Ad 5 (1ml). Postoperative four weeks and seven weeks of gated myocardial perfusion imaging evaluation of myocardial perfusion and changes in left ventricular ejection fraction (LVEF), and animals were killed in seven weeks, the TUNEL method was used to observe the apoptosis of myocardial cells, immunohistochemical examination evaluation transitional zone Bc1-2 and Bax protein expression, SMA and Ⅷ factor staining line transition zone vascular count. Results: Four weeks after the completion of the model, cardiac function between groups was no significant difference. Three weeks after transfection Ad 5 -HGF, myocardial perfusion and left ventricular ejection fraction of the treatment group improved significantly, especially in the high-dose treatment group. The TUNEL test results show that the decreased myocardial apoptosis index (apoptoticindex) of the medium dose and high-dose treatment group compared with the control group, the high-dose group decreased more significantly. Compared with the control group, middle dose and high-dose treatment group Bc1-2 protein expression increased Bax protein expression inhibition, a statistically significant difference, the more obvious the high-dose group. The large dose VIII factor α-SMA-positive vascular density was significantly increased, followed by a significant difference in dose treatment group, compared to the control group. No significant difference between the treatment and control groups in small doses to promote angiogenesis, reduce cardiac myocyte apoptosis and improve cardiac function. Although all indices of the high-dose and medium-dose treatment group was not statistically significant, but the cardioprotective effects of high-dose treatment group (1 × 10 10 Pfu) is more significant. Conclusion: The non-infarct-related artery the Ad transfected with different doses 5 -HGF can promote angiogenesis, inhibition of cardiomyocyte apoptosis, improve myocardial infarction, heart function, and to a large dose of Ad 5 -HGF transfection (1 × 10 10 Pfu) most significant myocardial protection.

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CLC: > Medicine, health > Internal Medicine > Heart, blood vessels ( circulatory ) disease > Heart disease > Myocardial diseases > Myocardial infarction
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