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肝缺血预处理保护作用与一氧化氮 内皮素 |
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of NO) and significant elevation of ET-1 in the blood plasma. The content of ALT, AST, LDH and TNF-α in blood plasma, and of MDA in liver tissue were increased but ATP in liver tissue was reduced, the hepatic damage was deteriorated. The protection of the hepatic IPC was concerned with the elevation of the ratio of NO/ET-1 caused by the elevation of NO-2/NO-3, and reduction of ET-1 as well. There was no iNOS mRNA detected in the liver tissues.CONCLUSION: Hepatic I/R injury is related to the disturbance of NO/ET-1. The protection of the hepatic IPC in the acute phase might be conducted by its regulation of NO/ET-1 system. The cNOS rather than the iNOS generated the NO in this situation. [MeSH] Liver; Reperfusion injury; Ischemia; Nitric oxide; Endothelins
近年研究发现一氧化氮/内皮素(nitric oxide/endothelins, NO/ETs)这一对最强烈的血管舒缩因子在肝缺血再灌注(ischemia/reperfusion,I/R)中发挥重要作用[1],并有研究认为肝缺血预处理(ischemic preconditioning,IPC)的保护机制与NO有关[2]。但对肝I/R急性期NO与内皮素-1(endothelin-1, ET-1)之间平衡关系的动态改变及其与肝I/R损伤的关系以及IPC对肝的保护作用是否与其对NO/ET-1系统的调节作用有关却研究得不多。本实验在鼠肝I/R模型 (Pringle's maneuver)上对此进行观察和研究。
材 料 和 方 法
一、动物分组及模型复制 Wistar大鼠共分3大组,即:假手术(sham operation)对照组(S组)(n=6)、肝缺血再灌注组(I/R组)及肝缺血预处理+肝缺血再灌注组(IPC+I/R组),I/R组及IPC+I/R组根据肝再灌注时间不同又分为A、C、D 3组(n=6),分别代表肝缺血40 min再灌注5 min(I40 min/R5 min)、I40 min/R60 min、I40 min/R120 min 3个时点。动物用1%戊巴比妥钠50 mg/kg腹腔注射麻醉,为缓解实验所致血容量不足,开腹前30 min所有动物由股静脉缓慢注入林格氏液(6 mL/kg)。取腹正中切口进腹,S组仅解剖肝十二指肠韧带而不阻断,I/R组解剖肝十二指肠韧带后用无损伤血管夹夹闭肝十二指肠韧带(Pringle's maneuver)以阻断肝动脉、门静脉血流40 min,再灌注时移去血管夹,恢复肝动脉、门静脉血流。IPC+I/R组先予以缺血预处理,即阻断肝十二指肠韧带5 min,放开5 min,反复3回,然后模型复制同I/R组,I/R组及IPC+I/R组均于再灌注不同时间结束实验。所有动物术前禁食12 h,自由饮水。 二、样品的采集 各组动物于实验结束时,经肝下下腔静脉穿刺至近肝静脉处抽血用于NO-2/NO-3、ET-1、肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α)及谷丙转氨酶(alanine aminotransferase, ALT)、谷草转氨酶(aspartate aminotransferase, AST)、乳酸脱氢酶(lactate dehydrogenase, LDH)水平的测定,分别取肝右叶组织两块,各约100mg用于肝组织三磷酸腺苷(adenosine triphosphate, ATP)及丙二醛(malondialdehyde, MDA)含量测定,取部分肝组织固定于10%福尔马林溶液上一页 [1] [2] [3] 下一页 上一个医学论文: 哮喘豚鼠内皮素 心钠素含量的变化及心钠素对内皮素含量的影响 下一个医学论文: 氧化低密度脂蛋白内皮受体在氧化低密度脂蛋白致内皮细胞损伤中的作用
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