Zhang Yong-Mei, Wei Er-Qing, Hu Xia, Xu Ming, Shi Yue, Zhang Jian-Fu
Department of Pharmacology, School of Medicine, Zhejiang University, 388, Yu Hang Tang Road, Hangzhou 310058, China.
Brain Res. 2008 May 30;1212:25-34. doi: 10.1016/j.brainres.2008.03.028. Epub 2008 Mar 27.
Our previous study demonstrated that electrical stimulation of the hypothalamic paraventricular nucleus (PVN) protects against gastric ischemia-reperfusion (GI-R) injury, but it is still unknown whether angiotensin II (Ang II) in the PVN plays a role in the development of GI-R. The purpose of this study was to investigate the effect of Ang II in the PVN on GI-R injury. GI-R injury was induced in rats by clamping the celiac artery for 30 min, and then reperfusing for 30 min, 1 h, 3 h, 6 h or 24 h, respectively. A cannula was inserted into the unilateral PVN for microinjection of Ang II. The extent of gastric mucosal damage was determined by gross and histological methods. We found that microinjection of pharmacological doses of Ang II (3, 30, and 300 ng) into the PVN dose-dependently inhibited GI-R injury, and that Ang II (30 ng) markedly attenuated GI-R injury at 1 h and 3 h after reperfusion. The effect of Ang II was prevented by pretreatment with the Ang II AT1 receptor antagonist losartan (5 microg) into the lateral cerebral ventricle. Furthermore, the protective effect of Ang II on GI-R injury was abolished by propranolol (1 mg/kg, i.v.) or disconnection of the nerves innervating the adrenal glands, was augmented by sympathectomy or phentolamine (1 mg/kg, i.v.), and was not affected by subdiaphragmatic vagotomy or atropine (1 mg/kg, i.v.). These results indicate that the PVN is a responsive site for central Ang II-induced protection against GI-R injury. The central effects of Ang II are mediated by AT1 receptors in the PVN, and the peripheral effects by a sympathetic-adrenal gland/beta-adrenoceptor pathway.
我们之前的研究表明，电刺激下丘脑室旁核（PVN）可预防胃缺血再灌注（GI-R）损伤，但PVN中的血管紧张素II（Ang II）在GI-R发生过程中是否发挥作用尚不清楚。本研究旨在探讨PVN中Ang II对GI-R损伤的影响。通过夹闭大鼠腹腔动脉30分钟，然后分别再灌注30分钟、1小时、3小时、6小时或24小时来诱导GI-R损伤。将套管插入单侧PVN用于微量注射Ang II。通过大体和组织学方法确定胃黏膜损伤程度。我们发现，向PVN微量注射药理剂量的Ang II（3、30和300 ng）可剂量依赖性地抑制GI-R损伤，且Ang II（30 ng）在再灌注后1小时和3小时可显著减轻GI-R损伤。向侧脑室预先注射Ang II AT1受体拮抗剂氯沙坦（5微克）可阻止Ang II的作用。此外，普萘洛尔（1毫克/千克，静脉注射）或切断支配肾上腺的神经可消除Ang II对GI-R损伤的保护作用，交感神经切除术或酚妥拉明（1毫克/千克，静脉注射）可增强该作用，而膈下迷走神经切断术或阿托品（1毫克/千克，静脉注射）对其无影响。这些结果表明，PVN是中枢Ang II诱导的预防GI-R损伤的反应位点。Ang II的中枢作用由PVN中的AT1受体介导，外周作用由交感-肾上腺/β-肾上腺素能受体途径介导。
