The Effects Of Curcumin On Nuclear Factor Kappa B,Peroxisome Proliferator-activated Receptor Gamma And BCL-2after Myocardial Infarction In Rats

Background Myocardial infarction (MI), one of the serious types of coronary heart disease (CHD), has high mortality and climbing morbidity. Meanwhile, the sufferers are much younger than before. Most of the patients cannot relief the occlusion of the affected coronary artery in time, so flow limitation causes cardiomyocyte necrosis and apoptosis. and then ventricular wall thinning, ventricular remodeling and heart failure. Using drugs to abate those pathophysiological processes is extremely important. Curcumin has been shown to possess extensive cardioprotective effects. But many exact deeper mechanisms remain unclear.Objectives This study was designed to evaluate the effects of curcumin on ischemia myocardium and the expression of nuclear factor kappa B(NF-κB). peroxisome proliterator-activated receptor gamma(PPAR-y). B-cell leukemia/lymphoma-2(BCL-2) after MI. Aim to explore the protective mechanisms of curcumin on myocardium.Methods1.40healthy SD rats were randomly assigned to3groups:blank control (BC) group (n=8), sham (SH) group (n=8), operation (OP) group (n=24).2.In the OP group,24hours after the anterior descending coronary artery was ligated, the survival rats were divided into myocardial infarction (MI) group (n=8) and curcumin (Cur) group (n=8) randomly. Rats in the SH group underwent thread-drawing without ligation. The BC rats weren’t treated with any operation. Rats in Cur were given curcumin100mg/(kg·d) orally, those in other groups were treated with oral administration of distilled water5ml/(kg·d). Daily oral treatment was repeated and continued for4weeks.3.HE staining was used to observe infarction area’s histopathological changes. TUNEL was to determine cardiomyocyte apoptosis around infarction area. The protein contents of PPAR-γ and NF-κB were estimated by immunohistochemical study. Use RT-PCR to study the expression levels of BCL-2mRNA.Results1. HE study of left ventricular myocardial cells of the BC group and the SH group demonstrated these cells arranged compact and orderliness, no necrosis and apoptosis. HE staining of cardiac muscle tissues of the MI group showed myocytolysis. disarray, inflammatory cells infiltration and collagen proliferation.The Cur group cells were better than those in MI, more cells survived, but still had necrosis and collagen proliferation et cetera.2. TUNEL analysis results:almost no apoptotic cells were found in the BC group and the SH group, apoptotic indexes (AI) between the two groups have no differences (P>0.05).Apoptotic cells of MI rats were significantly induced compared to BC rats and SH rats (P<0.001). Apoptotic cells of Cur group were much less than those of MI group (P<0.001). but still more than other two groups (P<0.001).3. The immunohistochemical assay showed that:the NF-κB protein of BC rats and SH rats was low expressed. The expression of such protein in MI group was increased significantly compared to the BC and the SH groups (P<0.01). The localization of NF-κB was suppressed in Cur group compared to MI group (P<0.01).It also showed that curcumin obviously improved the localization of PPAR-y in the nucleus in the Cur group compared to other groups (P<0.01). There was no significant difference in the expression of PPAR-γ between the BC. the SH and the MI groups (P>0.05).4. The results of RT-PCR showed that, with curcumin treatment, the expression levels of BCL-2mRNA in Cur rats were significantly increased compared to the MI rats (P<0.01). And myocardial infarction decreased BCL-2gene compared to the other three groups (P<0.01).Conclusions1. Curcumin reduces cardiomyocytes apoptosis after myocardial infarction and inhibits inflammatory cells infiltrating.2. Curcumin has cardioprotective effects. Such effects might be result from the combined influences of NF-κB、PPAR-γ、BCL-2.