Sildenafil as a Rescue Agent Following Intestinal Ischemia and Reperfusion Injury.
Sildenafil as a Rescue Agent Following Intestinal Ischemia and Reperfusion Injury.
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西地那非作为肠缺血和再灌注损伤后的救援剂。
DOI：
10.1016/j.jss.2019.09.037
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发表时间：
2020
期刊：
影响因子：
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通讯作者：
Markel,TroyA
中科院分区：
文献类型：
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作者：
Moore,HannahM;Drucker,NatalieA;Hosfield,BrianD;Shelley,WChris;Markel,TroyA
背景：急性肠系膜缺血具有很高的发病率。改善肠道血流参数的措施可能会改善疾病。西地那非是一种磷酸二酯酶5抑制剂，可增加环鸟苷单磷酸，并已被证明在损伤前给予可防止缺血的影响。然而，它作为一种救援剂的作用尚未得到证实。因此，我们假设西地那非作为肠缺血的救援剂，可以改善肠系膜灌注，限制肠上皮损伤，减少肠白细胞化学引诱剂。方法8 ~ 12周龄雄性C57BL/6J小鼠开腹手术，暂时阻断肠系膜上动脉60 min。缺血后允许再灌注，闭腹前腹腔注射不同浓度的西地那非。24 h后重新评估再灌注。对动物实施安乐死，评估肠道的组织学损伤和白细胞化学引诱剂。结果西地那非对肠缺血再灌注损伤后肠系膜灌注无改善作用。然而，在0.01 ~ 10mg /kg剂量范围内，西地那非确实改善了组织学损伤评分。100mg /kg剂量组小鼠组织学损伤无显著差异，1000mg /kg组小鼠均在损伤后24 h内死亡。上皮保护不能被激活调节的白细胞趋化剂、正常T细胞表达和分泌、巨噬细胞炎性蛋白1 α、单核细胞趋化蛋白、中性粒细胞激活蛋白或粒细胞集落刺激因子所促进。结论肠缺血后给予西地那非可限制肠黏膜损伤，但不会改变肠系膜灌注或白细胞化学引诱物内流。TypeBasic科学。证据水平
BackgroundAcute mesenteric ischemia carries a significant morbidity. Measures to improve blood flow parameters to the intestine may ameliorate the disease. Sildenafil, a phosphodiesterase 5 inhibitor, increases cyclic guanosine monophosphate and has been shown to prevent the effects of ischemia when given before injury. However, its effects as a rescue agent have not been established. We therefore hypothesized that sildenafil, when given as a rescue agent for intestinal ischemia, would improve mesenteric perfusion, limit intestinal epithelial injury, and decrease intestinal leukocyte chemoattractants.MethodsEight to 12 wk-old-male C57BL/6J mice underwent laparotomy and temporary occlusion of the superior mesenteric artery for 60 min. Following ischemia, reperfusion was permitted, and before closing the abdomen, sildenafil was injected intraperitoneally in a variety of concentrations. After 24 h, reperfusion was reassessed. Animals were euthanized and intestines evaluated for histologic injury and leukocyte chemoattractants.ResultsPostischemic administration of sildenafil did not improve mesenteric perfusion following intestinal ischemia and reperfusion injury. However, sildenafil did improve histologic injury scores in dose ranges of 0.01 to 10 mg/kg. No difference was noted in histological injury with 100 mg/kg dose, and all members of the 1000 mg/kg group died within 24 h of injury. Epithelial protection was not facilitated by the leukocyte chemoattractants Regulated on Activation, Normal T Cell Expressed, and Secreted, macrophage inflammatory protein 1 alpha, monocyte chemoattractant protein, neutrophil activating protein, or granulocyte colony stimulating factor.ConclusionsAdministration of sildenafil following intestinal ischemia may limit intestinal mucosal injury but does not appear to alter mesenteric perfusion or leukocyte chemoattractant influx.TypeBasic science.Level of evidenceN/A.