损毁大鼠下丘脑腹内侧核对应激引起的下丘脑c-Fos表达及胃运动的影响
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摘要
下丘脑腹内侧核(ventromedial hypothalamic nucleus,VMH)作为下丘脑基底部最大的核团,由于其边界清晰,目前对它的研究已较为深入。VMH最重要的功能是哺乳动物调控摄食的“饱(厌)食中枢”(satiety center)。已有的研究表明,VMH参与了胃运动的调控过程。李春林、苏海灵等实验发现,单侧电刺激VMH,胃蠕动频率和胃内压均显著降低。单侧电损毁VMH后,胃运动有逐渐加强的趋势。J.P.Duggan和D.A.Booth发现,电损毁VMH后几小时内,胃排空速率即加快,在1周后仍可观测到。R.M.Black等人电损毁VMH后记录胃排空速度,发现在第9天至第16天,VMH损毁自由进食组胃排空速度大于VMH损毁控制进食组和对照组。我们实验室已有的研究发现,在束缚-浸水应激条件下,出现胃运动机能亢进、胃酸分泌增多及急性胃粘膜损伤等现象,胃运动机能亢进是胃粘膜损伤的重要机制之一。但在束缚-浸水应激条件下,VMH对胃运动及应激性胃溃疡的影响还不清楚。我们实验室张玉玉研究发现,VMH、PVN和SON在束缚-浸水应激过程中均有c-Fos表达,说明VMH、PVN和SON都参与了束缚-浸水应激过程。而VMH、PVN和SON三者在束缚-浸水应激过程中的相互关系还不甚明了。因此,本文拟采用电损毁VMH以及c-Fos的方法观察VMH在束缚-浸水应激过程中对胃运动、应激性胃溃疡及PVN、SON的c-Fos表达影响,以探讨VMH在束缚-浸水应激胃溃疡产生中的作用以及VMH、PVN和SON三者在束缚-浸水应激过程中的相互关系。
     本研究分为两部分:
     第一部分,分别记录损毁双侧VMH后大鼠胃运动和胃粘膜损伤情况。实验分两组:一组为损毁大鼠双侧VMH后饲养5天,然后进行束缚-浸水应激,同时记录胃运动。结果发现,与对照组相比,损毁双侧VMH 5天后对大鼠进行束缚-浸水应激,胃运动的频率、幅度、时程、时程百分比、胃运动指数指标差异均不显著。另一组为损毁大鼠双侧VMH 16天后再进行束缚-浸水应激,同时记录胃运动。结果发现,与对照组相比,损毁双侧VMH 16天后对大鼠进行束缚-浸水应激,胃运动的频率、时程、时程百分比差异不显著。但是,胃运动幅度、胃运动指数有显著性差异。实验组的胃运动幅度和胃运动指数均远大于对照组。同时发现,损毁VMH 16天后对大鼠进行束缚-浸水应激,大鼠胃粘膜的损伤程度加重。产生这种结果的原因可能是损毁VMH后,胃运动增加,加重了胃粘膜的损伤。
     第二部分,电损毁大鼠双侧VMH后,观察束缚-浸水应激引起的下丘脑PVN和SON c-Fos表达的情况。结果发现,与对照组相比,损毁大鼠双侧VMH后束缚-浸水应激,PVN和SON的c-Fos表达均显著增强。表明在束缚应激浸水条件下,VMH对PVN和SON的活动具有抑制作用。
Ventromedial hypothalamic nucleus (ventromedial hypothalamic nucleus, VMH), as the largest nuclei at the base of hypothalamus, has been well studied because of its clear boundary. Large numbers of researchers have indicated that the most important function of VMH, known as "satiety center", was to control the feeding of mammalian. Previous studies suggested that, VMH is involved in the regulation of gastric motility. Li and Su reported that the frequency of gastric motility and intragastric pressure were significantly reduced when VMH was treated with unilateral electrical stimulation, while the gastric motility was increased after unilateral electrolytic lesion. J.P.Duggan and D.A.Booth’s studies revealed that gastric emptying rate was accelerated within a few hours after VMH lesions, and this phenomenon was still observed after 1 week. R.M.Black et al recorded that gastric emptying is significantly accelerated in day 9 to day 16 after VMH lesion, and ad libitum VMH-lesioned rats demonstrated faster than restricted VMH-lesiond and control rats in rates of gastric emptying. Our laboratory studies observed hyperactivity of the gastric motility, an increase in gastric acid secretion and acute gastric mucosal injury during restraint water-immersion stress, and found that gastric motor hyperactivity was an important reason of gastric mucosal injury. However, under restraint water-immersion stress ,the effect of VMH on gastric motility and gastric ulc er was unclear. Zhang found that restraint water-immersion stress increases expression of c-Fos protein in VMH, PVN and SON ,indicating that VMH, PVN and SON are involved in the process of restraint water-immersion stress. However, the relationship among VMH, PVN and SON was still unknown. Therefore, this present study was designed to examine the effect of VMH lesions on gastric motility、gastic ulcer and c-Fos expression in PVN, SON.To further explore the role of VMH in gastric ulcer induced by restraint water-immersion stress.
     This study was divided into two parts:
     The first part recorded gastric motility and gastric mucosal injury after bilateral VMH lesions. The experiment was divided into two groups: one group of rats were treated with restraint water-immersion stress and recorded the gastric motility 5 days after bilateral VMH lesions. The results showed that, compared to the control group ,there was no significant difference on frequency, amplitude, duration, time-percentage of gastric motility and gastric motility index . Another group of rats were treated with restraint water-immersion stress and recorded the gastric motility 15 day after bilateral VMH lesions. The results showed that, compared with the control group, the frequency, duration, time-percentage of gastric motility in lesion group was not significantly different. However, significant differences were detected among the amplitude, gastric motility index. The amplitude and gastric motility index were significantly larger than the control group. Aggravated gastric mucosal injury was also founded in 15 days lesion group.
     The second part observed SON and PVN c-Fos expression in restraint water-immersion stress after bilateral VMH lesions. The results showed that compared with the control group, c-Fos expression of SON and PVN was significantly enhanced. This indicated that VMH had an inhibition effect on the PVN and SON during restraint water-immersion stress.
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