Makarenko Irina G, Meguid Michael M, Gatto Louis, Chen Chung, Ramos Eduardo J B, Goncalves Carolina G, Ugrumov Michael V
Department of Surgery, Surgical Metabolism and Nutrition Laboratory, Neuroscience Program, SUNY Upstate Medical University, 750 East Adams Street, Syracuse, NY 13210, USA.
Neurosci Lett. 2005 Aug 5;383(3):322-7. doi: 10.1016/j.neulet.2005.04.031.
Tumor growth leads to anorexia and decreased food intake, the regulation of which is via the integrated hypothalamic peptidergic and monoaminergic system. Serotonin (5-HT), an anorectic monoamine acts primarily via 5-HT 1B-receptors in hypothalamic nuclei while neuropeptide Y (NPY) acts an orexigenic peptide. We previously reported that 5-HT 1B-receptors are up regulated while NPY is down regulated in tumor-bearing (TB)-related anorexia, contributing to food intake reduction. In anorectic TB rats we hypothesize that after tumor resection when food intake has reverted to normal, normalization of 5-HT 1B-receptor and NPY will occur. The aim of this study was to demonstrate normalization of these hypothalamic changes compared to Controls. In anorectic tumor-bearing rats after tumor resection (TB-R) and in sham-operated (Control) rats, distribution of 5-HT 1B-receptors and NPY in hypothalamic nuclei was analyzed using peroxidase antiperoxidase immunocytochemical methods. Image analysis of immunostaining was performed and the data were statistically analyzed. Immunostaining specificity was controlled by omission of primary or secondary antibodies and pre-absorption test. Our results show that after TB-R versus Controls a normalization of food intake, 5-H-1B-receptor and NPY expression in the hypothalamus occurs. These data, discussed in context with our previous studies, support the hypothesis that tumor resection results not only in normalization of food intake but also in reversible changes of anorectic and orexigenic hypothalamic modulators.
肿瘤生长会导致厌食和食物摄入量减少,其调节是通过下丘脑肽能和单胺能系统的整合来实现的。血清素(5-羟色胺,5-HT)是一种厌食性单胺,主要通过下丘脑核中的5-HT 1B受体起作用,而神经肽Y(NPY)则是一种促食欲肽。我们之前报道过,在荷瘤(TB)相关的厌食症中,5-HT 1B受体上调而NPY下调,这导致了食物摄入量减少。在厌食的TB大鼠中,我们推测肿瘤切除后当食物摄入量恢复正常时,5-HT 1B受体和NPY也会恢复正常。本研究的目的是证明与对照组相比,这些下丘脑变化会恢复正常。在肿瘤切除后的厌食性荷瘤大鼠(TB-R)和假手术(对照)大鼠中,使用过氧化物酶抗过氧化物酶免疫细胞化学方法分析下丘脑核中5-HT 1B受体和NPY的分布。对免疫染色进行图像分析并对数据进行统计学分析。通过省略一抗或二抗以及预吸收试验来控制免疫染色的特异性。我们的结果表明,与对照组相比,TB-R后食物摄入量、下丘脑5-H-1B受体和NPY表达恢复正常。结合我们之前的研究讨论这些数据,支持了肿瘤切除不仅导致食物摄入量恢复正常,还导致厌食性和促食欲性下丘脑调节因子发生可逆性变化这一假设。