Glutamate microinjection into the hypothalamic paraventricular nucleus attenuates ulcerative colitis in rats
Glutamate microinjection into the hypothalamic paraventricular nucleus attenuates ulcerative colitis in rats
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DOI：
10.1038/aps.2013.140
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发表时间：
2014-02-01
影响因子：
8.2
通讯作者：
Liu, Zhang-bo
中科院分区：
文献类型：
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作者：
Li, Ting-ting;Zhang, Jian-fu;Liu, Zhang-bo
目的：观察下丘脑室旁核(PVN)注射谷氨酸对溃疡性结肠炎(UC)大鼠的影响，并探讨其作用机制。方法：成年雄性SD大鼠结肠内注入2，4，6-三硝基苯磺酸(100 mg/kg，50%乙醇)诱导UC。用结肠损伤评分(CDS)表示结肠黏膜损伤的严重程度。采用免疫组织化学、Western blotting、生化分析或酶联免疫吸附试验等方法评价结肠粘膜的病理变化。结果：下丘脑室旁核内微量注射谷氨酸(3、6、12mg3、6、12mg3、6、12 mg)可剂量依赖性地降低UC大鼠的CDS。向PVN或孤束核(NTS)内微量注射红藻氨酸(0.3mgKA)造成化学损伤后，这种保护作用被消除。向NTS内微量注射AVP-V1受体拮抗剂DPVDAV(200 Ng)也可阻止这种保护作用。下丘脑室旁核微量注射谷氨酸后，迷走神经放电频率明显降低。结论：下丘脑PVN激活对UC大鼠具有保护作用，其保护作用可能是通过激活NTS和迷走神经实现的。这些作用可能是通过抗氧化、抗凋亡和抗炎因子来实现的。
Aim: To investigate the effects of glutamate microinjection into hypothalamic paraventricular nucleus (PVN) on ulcerative colitis (UC) in rats and to explore the relevant mechanisms.Methods: 2,4,6-Trinitrobenzenesulfonic acid (100 mg/kg in 50% ethanol) was instilled into the colon of adult male SD rats to induce UC. A colonic damage score (CDS) was used to indicate the severity of the colonic mucosal damage. The pathological changes in the colonic mucosa were evaluated using immunohistochemistry, Western blotting, biochemical analyses or ELISA. Ten minutes before UC induction, drugs were microinjected into the relevant nuclei in rat brain to produce chemical stimulation or chemical lesion.Results: Microinjection of glutamate (3, 6 and 12 mu g) into the PVN dose-dependently decreased the CDS in UC rats. This protective effect was eliminated after kainic acid (0.3 mu g) was microinjected into PVN or into the nucleus tractus solitarius (NTS) that caused chemical lesion of these nuclei. This protective effect was also prevented when the AVP-V1 receptor antagonist DPVDAV (200 ng) was microinjected into the NTS. The discharge frequency of the vagus was markedly decreased following microinjection of glutamate into the PVN. Microinjection of glutamate into the PVN in UC rats significantly increased the cell proliferation and anti-oxidant levels, and decreased the apoptosis and Bax and caspase 3 expression levels and reduced the pro-inflammatory factors in the colonic mucosa.Conclusion: The activation of hypothalamic PVN exerts protective effects against UC, which is mediated by the NTS and vagus. The effects may be achieved via anti-oxidative, anti-apoptotic, and anti-inflammatory factors.