| Background and ObjectiveCongestive heart failure (CHF) is the ending period of all different cardiovascular diseases and clinically consisting of many distinct syndromes. It is known that its basic process is myocardial remolding, including myocardial hypertrophy, myocardial necrosis/apoptosis, myocardial fibrosis. In recent years, cytokine hypothesis contributed to CHF was been draw immense attention. There are two different categories of cytokine according to its effect: pro-inflammatory cytokine and anti- inflammatory cytokine. The former refer to tumor necrosis factor Alfa (TNF-a), interleukin-6(IL-6), interleukin-1, interleukin-18(IL-8), and so on. The latter consist of interleukin-10(IL-10), interleukin-13 and interferon-gamma. At present, some cytokine founded early, mainly including TNF-a and IL-6, have definitive influence in onset, improvement, exaggeration of chronic heart failure, but other cytokine have attached a little attentions. But, with the declaration of cancellation experiments about TNF-a antagonist curing heart failure, much more interests have been transferred to anti-inflammatory research and interactive relation between anti-inflammatory cytokine and pro-inflammatory cytokine. IL-18 founded recently is a member of pro-inflammatory family, some experiments demonstrate its affection contributing to hypertrophy of myocardium. So, deep understanding of interaction between two distinctly different cytokine is of significance. Besides lowering low density lipoprotein and total cholesterol, hydroxymethyl glutaryl coenzyme A reductase inhibitors (called statins) have pleiotropic effects , and been prescribing widely in treatment hyperlipidemia and first or second prevention to coronary heart diseases. Moreover, some clinical experiment found a few surprising benefits to chronic heart failure, although its explicit way producing effects has not illuminated with details.To further add cytokine hypothesis new contents and find a new therapy on heart failure, serum IL-18, IL-10, IL-18/IL-10 are observed in rates with chronic heart failure. Then simastatin effect on congestive heart failure is evaluated.Materials and Methods1. After 1 week common feed, male Wistar rats were taken to make animal CHF model by suprarenal aortic constriction operation, then they were fed normal food for 8 weeks, 10 rats were randomly taken to detect hemodynamic parameters, LVEDP was measured to be higher than 15mmHg, then remainders were randomly divided into two group: CHF-C group and CHF-S group, 8 male Wister rats with just isolation of abdominal aorta were taken as SH group. CHF-S group were given simastatin 5mg/ kg.d by intragastric administration. CHF-C group and SH group were given saline 10ml/kg.d for 4 weeks in same way before death.2. Hemodynamic parameters including systolic blood pressure(SBP),diastolic blood pressure(DBP), mean artery pressure(MAP), left ventricle end diastolic pressure(LVEDP),intra-ventricular pressure changes( + dp/dtmax,-dp/dtmax) were written down by canalizing from right carotid artery before death. Then obtain blood, and centrifuge, finally Serum concentrations of IL-18, IL-10 by means of enzyme linked immunosorbent assay (ELISA) were measured in every group. After isolate left ventricle and weigh it, finally LVMI (left ventricle /body weight) was calculated.3. Statistical assay: results were reported as mean±SD( x|-±s),the data were treated by SPSS 10.0 statistical software.Results1. Rats in CHF-C and CHF-S group appeared different extent in dyspnoea, hypo-activity, edema in 8th week. But similar appearance did not happen in SH group.2. Hemodynamic parameters in every group: Compared with SH group, MAP, + dp/dtmax and - dp/dtmax in CHF-C group were progressively decreased(P<0.05), while LVEDP was significantly increased(P<0.05); however compared with CHF-C, MAP, + dp/dtmax and—dp/dtmax in CHF-S group were increased remarkably (P<0.05), LVEDP was decreased significantly(P<0.05).3. Compared with SH group,IL-18,IL-10,IL-18/IL-10 in CHF-C group were progressively increased (P<0.05); however compared with CHF-C, IL-18,IL-10 JL-18/IL-10 in CHF-S group were decreased remarkably (P<0.05).4. LVMI was higher in CHF-C group with contrast to SH group (P<0.05 ) , after prevention with simastatin ,CHF-S group showed marked decrease in LVMI (P<0.05).5. Linear regression analysis indicated that LVMI correlated positively with IL-18(r=772, P<0.001); IL-18 correlated positively with IL-10 as well(r=0.777, P<0.001).Conclusions1. IL-18 may contribute to myocardial hypertrophy in process of congestive heart failure.2. Imbalance between TH1 and TH2 probably contribute to the deterioration of congestive heart failure.3. Probably through retrieving the imbalance of cytokine net, simastatin can enormously improve symptom and cardiac function in rats with heart failure.
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