Cytokines And Cardiac Function And Apoptosis Related Proteins In The Relationship Between Clinical And Experimental Research

Background and purpose: Congestive heart failure is a very popular clinical syndrome, the characteristic featrue of congestive heart failure is the progressive worsening of ventricular function despite of the absence of clinical apparence. The mechanism of this hemodynamic deterioration are not well known but perhaps may be related to the activation of cytokines, many investigations have found that cytokines have participated the onset of congestive heart failure recently. This study focused on these cytokines, in our clinical study we tried to find out the relationship between cytokines (TNF-alpha and IL-6) and cardiac function, and to investigate the changes of these cytokines after heart function had improved or through different etiology. In our experimental study we wanted to find out whether TNF- a and Bcl-2 and Bax were present in a model of congestive heart failure, to verify that myocardium could express TNF- a and to discuss the relationship between TNF- a and cell apoptosis relating proteins. Methods: In our clinical study, ELISA was used to determine serum levels of TNF- a and IL-6 in 57 patients with congestive heart failure and 20 healthy people. In our experimental study, Wistar rats were randomly divided into three groups (20 rats/each group). Heart failure group was induced by left coronary ligation and sham-operated group was performed by sham operations, treatment group with CHF were given with fozinopril (8mg/kg/day). After fed for three months, cardiac function was evaluated by polygraph system and myocardium was tested whether to express TNF- a and Bcl-2 and Bax with immunohistochemical method, Western blot was used to determine the level of TNF- a in myocardial tissue, and the myocardial level of Bcl-2 and Bax of these three groups were tested with image analysis. Results: The clinical study is as follows: 1 .Serum level of TNF- a and IL-6 in patients with heart failure were higher than healthy people (P<0.0l) ~, and serum level of TNF- a and IL-6 in patients with moderate to severe heart failure were higher than those with mild to moderate heart failure(P<0.0l) 2.The levels of TNF- a and IL-6 were similar due to different etiology(P> 0.05). 3.The TNF- a and IL-6 levels of moderate to severe heart failure patients decreased after cardiac function had improved (P <0.05) . The experimental study is as follows: 1. The mortality rate was higher in congestive heart failure group and treatment group than sham-operated group. 2. The hemodynamic state was severely deteriorated in congestive heart failure group than sham-operated group (P <0.01) .The hemodynamic state had improved in treatment group (P<0.05). 3. TNF- a and Bcl-2 and Bax were present within myocardium in these three groups, mainly localized in cardiac myocytes. 4. Western blot showed the myocardium content of TNF- a was higher in congestive heart failure group and treatment group than sham-operated group (P < 0.01). 5. Image analysis showed that the myocardium content of Bcl-2 and Bax were higher in congestive heart failure group and treatment group than sham-operated group (P<0.01). 6. Correlation analysis showed that the level of TNF- a was well related the Bax/Bcl-2 tite (P <0.01). 7. Light and electron microscopy examined the structural alterations of both myocyte and interstitial in congestive heart failure group. It showed that there were myofibrillar disruption and disarray, myocyte degeneration, disruption of mitochondria crest in rats with heart failure. The structural...