The Protective Effect of Capsaicin Receptor-Mediated Genistein Postconditioning on Gastric Ischemia-Reperfusion Injury in Rats
The Protective Effect of Capsaicin Receptor-Mediated Genistein Postconditioning on Gastric Ischemia-Reperfusion Injury in Rats
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DOI：
10.1007/s10620-010-1151-3
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发表时间：
2010-11-01
影响因子：
3.1
通讯作者：
Qiao, Wei-Li
中科院分区：
文献类型：
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作者：
Du, Dong-Shu;Ma, Xiao-Bo;Qiao, Wei-Li
为了研究辣椒素受体介导的染料木素后处理是否通过PI 3 K/Akt信号通路对大鼠胃缺血再灌注损伤具有保护作用，采用氯醛麻醉大鼠，阻断腹腔动脉30 min，再灌注60 min。在此胃缺血-再灌注损伤动物模型的基础上，在再灌注前5分钟经外周静脉给予染料木黄酮100、500或1,000 μ g/kg。500 μ g/kg的剂量是后处理的最佳剂量，在该剂量下，I-R诱导的胃损伤的严重程度显著降低。免疫组化显示胃粘膜细胞凋亡减少。辣椒素受体的特异性拮抗剂辣椒平（CPZ）给药（1，000 μ g/kg，i. v.）就在缺血之前辣椒素（50 mg/kg，s.c.）每天一次，持续4天，逆转染料木黄酮的保护作用。逆转录-聚合酶链反应（RT-PCR）和Western blotting显示，金雀异黄素组降钙素基因相关肽（CGRP）表达增加，而辣椒碱组和辣椒平组则无此变化。CGRP抑制剂CGRP 8 -37也可阻断染料木素降低胃粘膜损伤指数的作用。此外，PI 3 K抑制剂LY 294002（1.5 mg/kg）可逆转染料木素的保护作用。与genistein组相比，LY 294002组Akt磷酸化水平降低，提示辣椒素受体介导了genistein后处理的保护作用。激活的辣椒素敏感神经元分泌的CGRP在染料木素的保护作用中起重要作用。PI 3 K/Akt通路也参与了染料木素的保护作用。
No published study has addressed the effect of genistein postconditioning on gastric ischemia-reperfusion (GI-R) injury in rats.To examine whether capsaicin receptor-mediated genistein postconditioning protects against gastric ischemia-reperfusion injury via the PI3K/Akt signal pathway.Chloraldurat-anesthetized rats underwent occlusion of the celiac artery for 30 min, followed by 60 min of reperfusion. Based on this animal model of gastric ischemia-reperfusion injury, genistein at doses of 100, 500 or 1,000 mu g/kg was administered via peripheral vein 5 min before reperfusion. The dose of 500 mu g/kg was optimal for postconditioning, at which the severity of I-R-induced gastric injury significantly decreased. Immunohistochemistry also showed that gastric mucosal cell apoptosis decreased. Capsazepine (CPZ), a specific antagonist for the capsaicin receptor, was administered (1,000 mu g/kg, i.v.) just before ischemia. Capsaicin (50 mg/kg, s.c.) once a day for 4 days reversed the protective effects of genistein. Reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting showed increased calcitonin gene-related peptide (CGRP) expression in genistein group but not in capsazepine or capsaicin group. CGRP inhibitor CGRP8-37 also prevented the effects of genistein in decreasing gastric mucosal injury index. In addition, PI3K inhibitor LY294002 (1.5 mg/kg) reversed the protective effect of genistein. Compared with genistein group, Western blots also demonstrated decreased Akt phosphorylation in LY294002 group.Our data suggest that capsaicin receptors mediated the protective effects of genistein postconditioning. CGRP secreted by activated capsaicin-sensitive neurons played an important role in the protective effects of genistein. PI3K/Akt pathway was also involved in the protective effects of genistein.