Study Of The Expression Of COX-2in The Pvn And Myocardial Apoptosis Of Heart Failure

Background and Objective：In recent years,chronic heart failure morbidity and mortality significantly rise.Chronic heart failure has become an important public healthy problem. Along with themechanism research of heart failure,it is assumed that heart failure mainly involves theactivation of neuroendocrine cell factor and ventricular remodeling. A recent study foundsinflammation factor COX-2in PVN involved in chronic heart failure process, but themechanism has not clear entirely.Other studies have found that,the myocardial apoptosiscontributes to the phase of heart failure,which is significant to the development of the heartfailure.The objective of this research is to study the expression of COX-2in the PVN andmyocardial apoptosis of heart failure in rats,discussing the mechanism and the relationshipbetween the inflammation factors COX-2in the central nervous system and myocardialapoptosis in heart failure.To observe the expression of protein COX-2in the hypothalamicparaventricular nucleus and cardiac myocyte apoptosis and to explore the treatment ofheart failure after giving the NF-κB inhibitors PDTC and aldosterone inhibitors EPL drugtreatment.Methods:Seventy healthy mail Sprague-Dawley(SD)rats were randomly divided into fourgroups:sham group (n=10),heart failure group (n=20),PDTC group (n=20),eplerenonegroup(n=20).The surgery group were given surgical ligation to the left anterior descendingcoronary artery inducing heart failure which was after acute myocardial infarction,and thesham group is as control only stringing.We put saline,PDTC(150mg/kg/d) and EPL(30mg/kg/d) into the water respectively.After6weeks of the operation,we chose rats in eachgroup randomly,and then got hemodynamic measurement,enrol biometrics heart and brainspecimens.Homogenating brain tissue,extracting cytoplasm protein. Preparing myocardiumwax sample to observe the myocardiol cell morphology by using HE staining.Apoptotic cell in myocardium were determined by TUNEL.Measuring the expression of COX-2protein with western blot test.Results:1.The results of hemodynamic:LVEDP in the HF group was significantly highcompared to the sham group(P<0.05);LVEDP in the EPL group was significantly decreasedcompared to the HF group(P<0.05);LVEDP in the PDTC group has no differencecompared to HF group;±Dp/dt max in the HF groups were significantly decreasedcompared to the sham group(P<0.05);±Dp/dt max in the EPL groups were significantlyincreased compared to the HF group(P<0.05);±Dp/dt max in the PDTC groups was a littlehigher compared to the HF group(P＞0.05),there was no difference between PDTC groupand HF group in±dp/dt.2.The result of pathology:myocardial cell hurt is more seriously in HF group than thesham group.Myocardial cell in surgery group had become hypertrophy,elongateon,sepa-rated from each other and muscle fiber was disorder or fracture. The size of nucleus wasdifferent,part of the myocardial nuclei disappear.3.The result of COX-2expression in PVN of rats by immunofluorescence:Theimmune fluorescence intensity in PVN of HF rats is stronger than the sham group.Thefluorescence intensity of EPL group and PDTC group were between HF group and shamgroups.4.The result of COX-2expression in PVN of rats by Western blot: The level ofCOX-2in HF groups(0.82±0.10)were significantly increased compared to the sham group(0.35±0.09)(P<0.05);The level of COX-2was significantly decreased in EPL group(0.52±0.20)compared to the HF group (P<0.05);The level of COX-2was lower in PDTCgroup(0.71±0.10) than the HF group(P <0.05).5.The result of the myocardic apototic index with the TUNEL assay:The myocardicapototic indexin of heart failure rats(36.82±6.34)was higher than sham group rats(9.68±8.40)(P<0.05);The myocardic apoptotic index reduced significantly in the EPLgroup(24.21±6.44) compared to the HF group (P<0.05);The myocardic apototic indexin ofthe PDTC group(33.24±5.92)was reduced than HF group(P<0.05);And the myocardicapototic index and the expression COX-2in the hypothalamic paraventricular nucleus hassignificant correlation(r=0.98, P<0·05).Conclusion:1.The activation of COX-2increased significantly in rats of CHF,so COX-2participate in the process of heart failure．The EPL can restrain the expression of protein COX-2and postpone the development of heart failure.The PDTC can restrain theexpression of protein COX-2partly,but cannot obviously improve the function of heart.2.Myocardial apoptosis contributes to the phase of heart failure,and it is associatedwith progressive cardiac dysfunction.The EPL and PDTC can restrain the myocardialapoptosis of heart failure and postpone the development of heart failure.The cardiacmyocyte apoptosis and the expression COX-2in PVN has significant correlation.