The Changes Of Inflammatory Factors And Raas In PVN Of Chronic Congestive Heart Failure In Rats

Background and Objective：Heart failure is the end of varieties of cardiovascular disease. With the acceleration ofthe process of population aging and an increase in incidence of high blood pressure,coronary heart disease and other common cardiovascular disease, the incidence of heartfailure is gradually increased.In recent years, scholars has been concentrated to the field ofthe central nervous endocrine system and cytokines of pathophysiology in heart failure.Thehypothalamus is a center in the process of regulating activities of internal organs andneuroendocrine,especially in the hypothalamus nucleus(PVN) plays an important role inthe regulation of cardiovascular activity and fluid balance. Studies have shown thatmetabolic activity increased in the PVN neurons in heart failure, and PVN neurons activityenhanced in regional myocardial, Speculated that the hypothalamic paraventricular nucleuscardiovascular center site through various channels play a role in the development of heartfailure, but specific mechanisms and the relationship between each reaction is still in theresearch. In the process of chronic congestive heart failure, neurohormonal mechanismsinvolved in the regulation, Renin-angiotensin-aldosterone system (RAAS) is considered tobe one of the important regulatory mechanisms, Neurohormonal activation can increasemyocardial contractility and cardiac output in early stage, so as to maintain arterial bloodpressure and organ perfusion, to support body cycling, but excessive activation of theneuroendocrine system is harmful to the body. Previous studies have confirmed, the RAASsystem in PVN area of cardiovascular center is an important humoral factors regulatingsympathetic nerve activity.The purpose of this experiment is to study the changes of the protein cellinflammatory cytokines and content of RAAS system of the hypothalamic paraventricularnucleus in rats with heart failure，to explore the relationship between the two in thepathogenesis of heart failure；Secondly, to observe inflammatory factors whether was affected in the PVN of rats with heart failure who were given PDTC, in order to investigatethe possibility of inhibition of the activity of the NF-κB in the PVN. EPL whether tosuppress the generation of the central RAAS components. Thirdly, to analysis thecorrelation of inflammatory factors and composion of RAAS in the peripheral.Method：Wistar rats were randomly divided into SHAM group (n=10) and heart failuregroup(n=60). The latter is further divided into the PDTC treatment group (n=20), the EPLtreatment group (n=20) and the HF non-treatment group (n=20). Heart failure groupligation of the left anterior descending artery caused by acute myocardialinfarction-induced heart failure, the SHAM group only wear lines without ligation servedas controls. Drugs were intragastric administrated the second postoperative day, PDTC(150mg/kg/d), the EPL (30mg/kg/d),the HF non-treatment group and SHAM group weregiven saline. After4-6weeks, the brain, serum specimens will be taken. Frozen sectionimmunohistochemical detect the expression of TNF-a、COX-2、CRH、Ang II within PVN.Measuring the expression of TNF-a、COX-2、CRH、Ang II protein with western blot test.The protein content of TNF-a、COX-2、CRH、Ang II、ALD in Peripheral circulating bloodwas detected by ELISA.Results:1. The expression of TNF-a and COX-2detected by ELISA, Western Blot andimmunohistochemical. ELISA: heart failure non-treatmented group was significantlyhigher than the SHAM group (P <0.05), PDTC group and EPL group can reduce theexpression of these proteins, but still obviously higher than the SHAM group (P <0.05).Western Blot Testing: the absorbance of TNF-a and COX-2was most of maximum in heartfailure non-treated group, was significantly higher than sham-ope-rated group (P<0．05).The expression of proteins in PDTC group and EPL group were between HF non-treatedgroup and sham-operated group.2. The expression of serum NE and Ald by ELISA: Higher expression levels in heartfailure untreated group compared with SHAM group(P <0.05), EPL and PDTC reduced theexpression of NE and ALD and had a statistical significance(P <0.05), But stillsignificantly higher than the SHAM group.3. The expression of CRH, Ang Ⅱ in PVN byWestern Blot and immunohistoc-hemical: western blot showed that, compared with SHAM group, the absorbance of stripewas significantly higher in heart failure untreated group (P <0.05), PDTC group and EPL group can lower bands absorbance, but haven’t dropped to the level of SHA-M group (P<0.05). Immunohistochemistry showed that：positive cells expressed ve-ry little in thePVN of SHAM group rats. HF untreated group showed strong expres-sion in PVN，HFuntreated group expressed strongly positive, The protein positive are brownish yellowgranules and sporadic distributed in the paraventricular nucleus neurons and glial cellsintracytoplasmic. The PDTC reduce the brown particles expre-ssion in PVN.4. Cytokines and RAAS components in peripheral blood are positively correlated.TNF-aand Ald, COX-2was highly positively correlated (P <0.05), TNF-a and NE was amoderate positive correlation (p <0.05), COX-2and NE, Ald was highly positivelycorrelated (p <0.05), NE with Ald are highly positively correlated (p <0.05).Conclusion:1. The llevels of TNF-a, COX-2was increased in peripheral and central in heartfailure rat, prompt inflammatory factors involved in heart failure process, inflam-matoryfactors was highest in HF untreated group, least in SHAM group, exlpaining that the levelsof inflammatory factors associated with the severity of heart failure.2. Central CRH levels in heart failure rats was significantly higher than the SHAMgroup，Sympathetic activated，the expression of outer periphery NE, ALD and central AngⅡi ncreased.EPL reduced sympathetic activity and expression of NE, Ang Ⅱ, ALD wasdecreased.Description HPA axis is activated in heart failure, and involved in thedevelopment of heart failure through the influence of sympathetic nerve activity.3.EPL and PDTC can reduce the expression of inflammatory in the PVN andperipheral, and reduce the activity of the RAAS to some extent.4.Cytokines and the components are positively correlated, they interact with eachother and jointly promote the development of heart failure.