摘要
目的探讨nesfatin-1对大鼠下丘脑弓状核（ARC）ghrelin敏感性胃牵张（GD）神经元放电活动和胃运动的调控作用。方法选用成年Wistar大鼠132只，采用细胞外单位神经元放电及核团微量注射方法，记录ARC注射ghrelin后GD敏感神经元的放电变化并鉴定ghrelin敏感性GD神经元；随后向ghrelin敏感性GD神经元注射nesfatin-1，观察其放电变化。另取大鼠48只，ARC分别微量注射0．5μL生理盐水（NS）、2×10^3nmol／L的nesfatin-1、2×10^4 nmol／L的nesfatin-1、2×10^5nmol／L的nesfatin-1、10^5nmol／L的黑色素受体拮抗剂（SHU9119）及2×10^4nmol／L的nesfatin1＋10^5nmol／L的SHU9119混合液（各8只），采用胃内置入应力传感器的方法，记录各组清醒自由活动大鼠胃收缩幅度和频率的变化。结果ARC共记录到246个神经元放电，164个为GD敏感神经元。在88个GD兴奋性（GD-E）神经元中，ARC微量注射ghrelin可兴奋其中62个神经元。而在76个GD抑制性（GD-I）神经元中，ghrelin可抑制其中47个神经元。ARC注射nesfatin-1可抑制其中39个ghrelin敏感性GD-E神经元，放电频率显著降低（t=8．57，P〈0．01）；而在47个ghrelin敏感性GD-I神经元中，nesfatin-1可兴奋其中25个神经元，放电频率显著增加（t=8．07，P〈0．01）。nesfantin-1对ghrelin敏感性GD神经元电活动的作用可被SHU9119部分阻断（t=2．39、2．22，P〈0．05）。体内胃运动研究结果显示，ARC微量注射不同浓度的nesfatin-1于5min后，胃收缩幅度和频率均显著降低（F=3．30～5．27，q=3．34～17．74，P〈0．05）。SHU9119可以部分阻断nesfatin-1对胃运动的抑制效应（t=2．22、2．93，P〈o．05）。结论下丘脑ARC的nesfatin-1能够影响大鼠ghrelin敏感性GD神经元的放电并抑制胃运动，而该效应可能通过黑色素神经通路来完成。
Objective To explore the effects of nesfatin-I in arcuate nucleus （ARC） on ghrelin responsive gastric distension （GD） neurons and gastric motility in rats. Methods This study consisted of 132 adult Wistar rats. The effects of nesfatin- 1 on ghrelin responsive GD neurons in the ARC were observed by recording extracellular discharges of single unit neuron. Another 48 rats were evenly divided into six groups, and a microinjection of 0.5 μL of the following solutions i. e. NS, 2 ×10^3 nmol/L nesfatin-1, 2 ×10^4 nmol/L nesfatin-L, 2 ×10^5 nmol/L nesfatin-L, 105 nmol/L SHU9119 （an antagonist of melanocortin 3/4 receptor） or 2 ×10^4 nmol/L nesfatin-1 ＋ 105 nmol/L SHU9119 was injected into the ARC, respectively. The changes of amplitude of constriction and frequency of gastric motility were monitored in conscious rats by a transducer planted into the stomach. Results Of 246 recorded neurons in ARC, 164 neurons were GD responsive neurons. In 88 GD-E neurons, microinjection of ghrelin to the ARC could excite 62 of the neurons, while in 76 GD-I neurons, 47 of the neurons could be inhibited by ghrelin , injection of nesfatin-1 could inhibit 39 ghrelin responsive GD-E neurons with the firing rate significantly decreased （t = 8.57 ,P〈0.01）, while excited 25 ghrelin responsive GD-I neurons with the firing rate notably increased （t = 8.07 ,P〈0.01）. However, pretreatment with SHU9119 could partially block the responses of ghrelin responsive GD neurons induced by nesfatin-l （t = 2.39,2.22; P〈O.05）. Five minutes after microinjection of nesfatin-L, the amplitude and frequency of the gastric motility significantly reduced in a dose-dependent manner （F=3.30-5.27,q=3.34-17.74,P〈0.05）. SHU9119 could partially block the depression effect induced by nesfatin-l （t = 2. 22, 2.93;P〈0.05）. Conclusion Nesfatin-I can serve as an inhibitory factor in ARC to regulate gastric motility via melanocortin pathway and influence the firing activity of ghrelin responsive GD neurons.
出处
《青岛大学医学院学报》
CAS
2014年第2期98-101,共4页
Acta Academiae Medicinae Qingdao Universitatis
基金
国家自然科学基金资助项目(No.30470642
No.30670780
No.31071014
No.81100260
No.81270460)
山东省科技攻关项目(2008GG10002006)
山东省卫生厅项目(2007-HZ026)
青岛市科技局项目(11-2-3-3-(2)-nsh
13-1-4-170-jch)
