大黄素与施他宁对重症胰腺炎胰缺血的治疗作用及机制

Effect of emodin and stilamin on pancreatic ische mia in acute hemorrhagic necrotizing pancreatitis and its mechanism

目的：研究重症胰腺炎（ＡＨＮＰ）胰组织血流的动态变化以及大黄素和施他宁的作用，了解两药对胰缺血这一决定ＡＨＮＰ病理类型的重要因素的影响。方法：以牛磺胆酸钠诱发大鼠ＡＨＮＰ模型，用ＬＳⅢ型组织血流仪计算机自动平衡跟踪测定胰组织血流，放射免疫法测定二十碳烯酸类异常代谢产物。结果：ＡＨＮＰ初期胰组织血流显著降低；与非治疗组比较，大黄素组血流降低被显著阻遏，总下降值显著小于非治疗组，也小于施他宁组；而施他宁组在发病前即因前列腺素Ｅ２（ＰＧＥ２）给药出现胰组织血流降低，但发病后降低较非治疗组显著减轻。非治疗组血浆血栓素Ｂ２（ＴＸＢ２）显著增高，发病６小时达假手术组的４．５倍；６酮前列腺素Ｆ１α（６ｋｅｔｏＰＧＦ１α）和ＰＧＥ２则呈下降趋势。大黄素或施他宁组上述二十碳烯酸类异常代谢被显著调整。给药的两组１２小时生存率显著高于非治疗组。病理组织学评分及电镜观察示两给药组病理损害显著轻于非治疗组。结论：ＡＨＮＰ初期胰缺血经应用大黄素或施他宁后得以显著改善，此可能是抑制二十碳烯酸类异常代谢所致。两药改善微循环、增强细胞保护机制的作用有益于ＡＨＮＰ治疗。

Objective:To investigate dynamic changes in pancreatic tissue blood flow (PTBF) in acute hemorrhagic necrotizing pancreatitis (AHNP) and effects of stilamin or emodin on pancreatic ischemia,one of the major factors which determine pathologic types of AHNP.Methods:AHNP was induced by sodium taurocholate in rats,PTBF was monitored with computerized tissue blood formatter (Model LSⅢ).Radioimmunoassay was employed to determine abnormal metabolism of eicosanoids.Results:There was a significant decrease of PTBF in the early stage of AHNP,while a significant improvement of PTBF was found in emodin group compared with untreated group.Total volume of decreased PTBF in emodin group was significantly diminished compared with both untreated group and stilamin group.A decreased PTBF was observed following infusion of PGE 2 (before induction of AHNP),but it was significantly improved in stilamin group compared with controls after AHNP.In untreated group,plasma TXB 2 was 4 5 times higher than that in shamoperated group while 6ketoPGF 1α and PGE 2 tended to decrease at 6 hours after AHNP.These abnormal changes were markedly ameliorated both in emodin and stilamin groups.Moreover,mortality and acinic cell damage,which evaluated under pathologic scoring or transmission electron microscope,were significantly reduced by treated with either emodin or stilamin.Conclusions:Both emodin and stilamin can partly reverse decrease of PTBF in the early stage of AHNP,which may be associated with inhibition of abnormal eicosanoids synthesis.All these effects may improve microcirculation and cytoprotection,and will be beneficial for the treatment of AHNP.