Wahab Fazal, Tazinafo Lucas F, Cárnio Evelin C, Aguila Fábio A, Batalhão Marcelo E, Rocha Maria José A
Department of Morphology, Physiology and Basic Pathology, School of Dentistry of Ribeirão Preto, Avenida do Café s/n CEP, Ribeirão Preto, SP, 14040-904, Brazil.
Endocrine. 2015 May;49(1):215-21. doi: 10.1007/s12020-014-0452-2. Epub 2014 Oct 22.
The aim of this study was to analyze the effect of IL-1ra (an Interleukin-1 receptor antagonist) on sepsis-induced alterations in vasopressin (AVP) and nitric oxide (NO) levels. In addition, IL-1ra effect on the hypothalamic nitric oxide synthase (NOS) activities and survival rate was also analyzed. After Wistar rats were intracerebroventricular injected with IL-1ra (9 pmol) or vehicle (PBS 0.01 M), sepsis was induced by cecal-ligation and puncture (CLP). Blood, CSF, and hypothalamic samples were collected from different groups of rats (n = 8/group) after 4, 6, and 24 h. AVP and NO levels were greatly increased in CLP. Both total NOS and inducible NOS (iNOS) activities were also greatly increased in CLP rats. These changes in AVP, NO, and NOS were not observed in sham-operated control rats. IL-1ra administration did not alter plasma AVP levels after 4 and 6 h as compared to vehicle in CLP animals but after 24 h were significantly (P < 0.01) higher in IL-1ra-treated animals. IL-1ra administration significantly (P < 0.01) decreased NO concentration in CSF but not in plasma. Both total NOS and iNOS activities were also significantly decreased by IL-1ra at 24 h in CLP animals. Moreover, the 24 h survival rate of IL-1ra-treated rats increased by 38 % in comparison to vehicle administered animals. The central administration of IL-1ra increased AVP secretion in the late phase of sepsis which was beneficial for survival. We believe that one of the mechanisms for this effect of IL-1ra is through reduction of NO concentration in CSF and hence lower hypothalamic iNOS activities in the septic rats.
本研究旨在分析白细胞介素-1受体拮抗剂（IL-1ra）对脓毒症诱导的血管加压素（AVP）和一氧化氮（NO）水平变化的影响。此外，还分析了IL-1ra对下丘脑一氧化氮合酶（NOS）活性和存活率的影响。将Wistar大鼠脑室内注射IL-1ra（9 pmol）或溶剂（0.01 M PBS）后，通过盲肠结扎和穿刺（CLP）诱导脓毒症。在4、6和24小时后，从不同组的大鼠（每组n = 8）中采集血液、脑脊液和下丘脑样本。CLP组中AVP和NO水平大幅升高。CLP大鼠的总NOS和诱导型NOS（iNOS）活性也大幅增加。在假手术对照大鼠中未观察到AVP、NO和NOS的这些变化。与CLP动物中的溶剂相比，IL-1ra给药在4和6小时后未改变血浆AVP水平，但在24小时后，IL-1ra处理的动物中血浆AVP水平显著升高（P < 0.01）。IL-1ra给药显著降低了脑脊液中的NO浓度，但未降低血浆中的NO浓度。在CLP动物中，IL-1ra在24小时时也显著降低了总NOS和iNOS活性。此外，与给予溶剂的动物相比，IL-1ra处理的大鼠24小时存活率提高了38%。脓毒症后期中枢给予IL-1ra可增加AVP分泌，这对存活有益。我们认为，IL-1ra产生这种作用的机制之一是通过降低脑脊液中的NO浓度，从而降低脓毒症大鼠下丘脑的iNOS活性。
