Central actions of the chemokine stromal cell-derived factor 1 contribute to neurohumoral excitation in heart failure rats.
Central actions of the chemokine stromal cell-derived factor 1 contribute to neurohumoral excitation in heart failure rats.
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DOI：
10.1161/hypertensionaha.111.188086
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发表时间：
2012-05
期刊：
影响因子：
--
通讯作者：
Felder RB
中科院分区：
文献类型：
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作者：
Wei SG;Zhang ZH;Yu Y;Weiss RM;Felder RB
趋化因子及其受体在大脑神经元中的大量表达表明，它们在协调炎症和免疫反应之外发挥着功能作用。越来越多的证据表明，脑趋化因子在调节神经元活动和神经激素释放。本研究探讨了脑趋化因子在缺血性心力衰竭（HF）大鼠血流动力学、交感神经和神经内分泌机制调节中的潜在作用。免疫组化分析显示趋化因子基质细胞衍生因子-1 (SDF-1)/CXCL12在下丘脑室旁（PVN）和皮质下器官中高表达，且与假手术（SHAM）对照大鼠相比，HF大鼠的SDF-1表达显著升高。脑室内注射SDF-1可诱导SHAM和HF大鼠血压（BP）、心率（HR）和肾交感神经活动（RSNA）持续升高，但HF大鼠的反应被夸大。向PVN双侧微量注射SDF-1也可引起HF大鼠血压、HR和RSNA的显著升高。ICV输注SDF-1 4小时后，正常大鼠血浆精氨酸抗利尿激素（AVP）、促肾上腺皮质激素（ACTH）和去甲肾上腺素（NE）水平升高，而ICV SDF-1短发卡RNA （shRNA）预处理可阻止这种反应。体外注射SDF-1 shRNA也可降低HF大鼠血浆AVP、ACTH和NE水平。这些数据表明，在正常和病理生理条件下，趋化因子SDF-1在调节交感神经驱动、神经内分泌释放和血流动力学功能中起重要作用，因此可能参与HF的神经和体液激活。
The ample expression of chemokines and their receptors by neurons in the brain suggests that they play a functional role beyond the coordination of inflammatory and immune responses. Growing evidence implicates brain chemokines in the regulation of neuronal activity and neurohormonal release. This study examined the potential role of brain chemokines in regulating hemodynamic, sympathetic and neuroendocrine mechanisms in rats with ischemia-induced heart failure (HF). Immunohistochemical analysis revealed that the chemokine stromal cell-derived factor-1 (SDF-1)/CXCL12 was highly expressed in the hypothalamic paraventricular (PVN) and subfornical organ, and that SDF-1 expression was significantly increased in HF rats compared with sham-operated (SHAM) control rats. Intracerebroventricular (ICV) injection of SDF-1 induced substantial and long-lasting increases in blood pressure (BP), heart rate (HR) and renal sympathetic nerve activity (RSNA) in both SHAM and HF rats, but responses were exaggerated in HF rats. Bilateral microinjection of SDF-1 into the PVN also elicited exaggerated increases in BP, HR and RSNA in the HF rats. A 4-hour ICV infusion of SDF-1 increased plasma levels of arginine vasopressin (AVP), adrenocorticotropic hormone (ACTH) and norepinephrine (NE) in normal rats, responses that were prevented by pretreatment with ICV SDF-1 short-hairpin RNA (shRNA). ICV administration of SDF-1 shRNA also reduced plasma AVP, ACTH and NE levels in HF rats. These data suggest that the chemokine SDF-1, acting within the brain, plays an important role in regulating sympathetic drive, neuroendocrine release, and hemodynamic function in normal and pathophysiological conditions, and so may contribute to the neural and humoral activation in HF.