The Experimental Studies On Treating Chronic Congestive Heart Failure Using Bcl-2 Gene

[BACKGROUD]It is recognized recently that the repeated losing of myocardial cells is the most important factor in the course of heart failure, the losing may result from the apoptosis of myocardial cells, and the death of myocardial cells caused by apoptosis is closely related to the ventricular remodeling. More and more attention was given to the investigations of the decreasing of myocardial cells caused by apoptosis.Apoptosis is controlled by gene coding. There're many genes which control apoptosis. Recent investigations indicate that bcl-2 gene inhibits the cell apoptosis directly. If the bcl-2 genes were introduced into the failured myocardium using gene vector and transfer techniques, they will inhibit the apoptosis of myocardial cells, decrease the losing of myocardial cells, and improve the cardiac function.We used the non-virus vector—polyethylenimine to make the bcl-2 gene express in myocardial cells to decrease the apoptosis of myocardial cells and improve the cardiac function.[METHOD]We made the models of chronic heart failure using abdominal aorta ligation method. The models were divided into two groups randomly: the experiment group and control group. The experiment group was injected in-vivo-jet-PEI-bcl2-GFP to transfect the myocardial cells. After 1, 3, 7 days, we observed the expressions of GFP and Cy3 in the myocardium slices under the con focal laser microscopeusing antibody staining method, then detected the change of the expression of Bcl-2 protein using two-step histostaining method, labeled the apoptotic cells with TUNEL methods, and check the cardiac functions with multi-channel polygraph system such as heart rate(HR), central venous pressure(CVP), cardiac output(CO), left ventricular end diastolic pressure(LVEDP), et al. The control group was injected the same dose of in-vivo-jet-PEI as the experiment group. [RESULTS]1. 1 day after the bcl-2 genetic drugs contained GFP reporter gene was injected into the myocardium of Wistar rats, the GFP expressed significantly high, and the abundance of the Cy3 was high.2. Compared to the control group, the injection of genetic drugs could decrease the incidence of apoptosis in all experiment groups of 1, 3, 7 days after injection.3. The expressions of Bcl-2 protein in experiment groups were significantly higher than the control group.4. The cardiac function of all experiment groups tended to improve. [CONCLUSIONS]1. The apoptosis of myocardial cells in experiment groups increases significantly, and the cardiac function decreases.2. The expressions of Bcl-2 protein in experiment groups decrease significantly.3. The expressions of GFP and Cy3 indicate: thein-vivo-jet-PEI-bcl2-GFP DNA we constructed can express effectively in the myocardium of models which suffered from chronic heart failure.4. The in-vivo-jet-PEI-bcl2-GFP DNA we constructed can inhibit the apoptosis of myocardial cells of models which suffered from chronic heart failure.5. The in-vivo-jet-PEI-bcl2-GFP DNA we constructed can improve the cardiac function after transfecting the myocardium.