The Study Of Neuroendocrine Activition And Inflammatory Cytokines In PVN

Background and ObjectiveCongestive heart failure is the most common end stage of cardiovascular diseases,although in recent years, with the deepening of heart failure mechanism, more and moremethods of treatment are using in clinical, the mortality rate is still high, and HF is still aserious threat to human health. Therefore, to explore the mechanism of heart failure isalways a hot topic of scientific research workers. In recent years, more and moreexperiment proved that inflammatory cytokines play an important role in the process ofheart failure. Among these inflammatory cytokines, IL-1is the initial factor ofinflammatory cytokine, and rised levels of IL-1has been confirmed both in the circulationand in the failing heart itself in patients of heart failure. Recent studies have found that, inthe central nervous system there are also increased expression of IL-1, and its specificmechanisms are still unclear. This study intends to use the NF-κB inhibitor pyrrolidinedithiocarbamate (PDTC) and mineralocorticoid receptor blocker eplerenone (EPL)intervention on heart failure rats, to observe the changes of PVN neurons and the activationof peripheral and central IL-1β、 CRH expression, and estimate its role in heart failureprocess.MethodsHealthy adult Wistar rats were divided into operation group and sham operationcontrol group (n=20), operation group was further divided into PDTC treatmentgroup(n=20), EPL treatment group (n=20) and untreated group (n=20). Operation groupunderwent ligation of the left anterior descending coronary artery to induce acutemyocardial infarction, sham operation group only thread in the same location withoutligation as the control. Then these rats were administrated with PDTC (150mg/kg/d),EPL(30mg/kg/d) and clean distilled water. After six weeks, hemodynamic data wasmeasured, and hypothalamus, serum samples were collected. Enzyme linkedimmunosorbent assay was used to detect the serum content of IL-1β; And the levels ofFra-like, IL-1β, CRH was detected by immunohistochemistry and Western Blot. Results1.The results of hemodynamics: LVEDP in HF group was significantly higher thanthat in sham operation group rats (P<0.05); compared with the sham operation group rats±dp/dt Max in heart failure rats were significantly decreased (P<0.05).2.The results of IL-1β expression in serum: HF rats had a significantly increasedIL-1β expression in serum (243.56±32.37) compared with SHAM group (58.45±12.38),P<0.05; And both the IL-1β expression in PDTC group(157.26±14.43) and EPL group ratswas significantly lower than the HF group, P<0.05.3.The results of IL-1β, Fra-like, CRH expression in PVN by immunohistochemistry:HF group had more positive cells compared with sham operation group. the number ofpositive cells in EPL group and PDTC group were between HF group and SHAM group.4.IL-1β, Fra-like, CRH expression in PVN by Western blot: in heart failure group theexpression of IL-1beta, Fra-like, CRH were all significantly higher than those in theSHAM group, P<0.05; rats in treated with EPL had decreased IL-1β, Fra-like, CRHexpression than the HF group(P<0.05), the expression of IL-1β, Fra-like CRH in PDTCgroup were also lower than the HF group (P<0.05).Conclusion1. The expression of Fra-like protein in the hypothalamus of rats was significantlyincreased in heart failure, PVN neurons were activated in the process of heart failure.2. The expression of CRH in the PVN of heart failure rats increased, and HPA axisactivation increased peripheral sympathetic nerve activity.3. The number of IL-1β positive cells in the hypothalamus paraventricular nucleus ofheart failure rats increased, and higher level IL-1β concentration in plasma, indicate thatIL-1β is involved in the occurrence and development of heart failure.4. Rats with EPL administration had increased Fra-like, IL-1β content in thehypothalamus paraventricular nucleus than untreated group, suggesting that EPL caneffectively reduce the PVN neuron activation, and reduce proinflammatory cytokineexpression of IL-1β.5. PDTC treatment can reduce the neuronal activation in rats of heart failure PVN,and reduce the expression of IL-1β.