Activation of central nesfatin-1/NucB2 after intraperitoneally administered cisplatin in rats
Activation of central nesfatin-1/NucB2 after intraperitoneally administered cisplatin in rats
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DOI：
10.1016/j.bbrc.2017.06.119
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发表时间：
2017-08-26
影响因子：
3.1
通讯作者：
Ueta, Yoichi
中科院分区：
文献类型：
--
作者：
Akiyama, Yasuki;Yoshimura, Mitsuhiro;Ueta, Yoichi
顺铂作为一种抗癌药物被广泛使用，但也有多种不利的副作用，包括食欲不振，折磨着患者。Nesfatin-1/NucB 2是一种神经肽，广泛表达于中枢神经系统和外周器官。在本研究中，我们研究了腹腔内（i. p.）顺铂对中枢nesfatin-1/NucB 2的作用。在成年雄性Wistar大鼠（180-220 g）中腹膜内给予生理盐水（作为对照）或顺铂（6 mg/kg溶于生理盐水）。与对照组相比，顺铂腹膜内给药后至少24 h的累积摄食量明显受到抑制，体重在24 h时显著降低。腹腔给药后90 min行灌流，然后进行Fos和nesfatin-1/NucB 2的双重免疫组化。腹腔注射顺铂后，下丘脑和脑干内nesfatin-1/NucB 2免疫反应阳性神经元表达Fos的百分比明显增加。与nesfatin-1/NucB 2-错义治疗组相比，脑室内施用nesfatin-1/NucB 2-反义导致在腹膜内施用顺铂后2小时食物摄入减少的显著减弱。这些结果表明，腹腔注射顺铂至少部分激活了CNS中的nesfatin-1/NucB 2神经元，并可能在大鼠中发挥促凋亡作用。(C)2017爱思唯尔公司All rights reserved.
Cisplatin, known as an anticancer drug, has been widely used; however, diverse disadvantageous side effects, including appetite loss, afflict patients. Nesfatin-1/NucB2, discovered as an anorexic neuropeptide, is broadly expressed in the central nervous system (CNS) and peripheral organ. In the present study, we examined the effects of intraperitoneally (i.p.) administered cisplatin on central nesfatin-1/NucB2. Saline, as control, or cisplatin (6 mg/kg dissolved in saline) was i.p. administered in adult male Wistar rats (180-220 g). Cumulative food intake was remarkably suppressed for at least 24 h and body weight was significantly smaller at 24 h after i.p. administration of cisplatin compared to control group. At 90 min after i.p. administration, they were perfused, followed by carrying out doubleimmunohistochemistry for Fos and nesfatin-1/NucB2. The percentage of nesfatin-1/NucB2 immunoreactive neurons expressing Fos was marked increased in the hypothalamus and brainstem after i.p. administration of cisplatin. Intracerebroventricularlly administered nesfatin-1/NucB2-antisense resulted in a significant attenuation of decreased food intake for 2 h after i.p. administration of cisplatin compared to nesfatin-1/NucB2-missense treated group. These results suggest that i.p. administration of cisplatin activated, at least in part, nesfatin-1/NucB2 neuron in the CNS and may exert anorexigenic effects in rats. (C) 2017 Elsevier Inc. All rights reserved.