急性坏死性胰腺炎大鼠胰生长抑素受体的变化与奥曲肽治疗的作用机制

Changes of somatostatin receptor of pancreas and effectiveness of octreotide on acute necrotizng pancreatitis in mice

目的 研究急性坏死性胰腺炎 (ANP)时胰生长抑素受体 (SSTR)的表达、胰组织血流改变及其与二十碳烯酸代谢的关系 ,探讨生长抑素类似剂奥曲肽治疗ANP的作用机制。方法 以牛磺胆酸钠胰胆管注射诱发大鼠ANP模型 ,作12 5I 生长抑素 14受体放射配基结合实验 ,原位杂交检测胰组织SSTR2mRNA表达 ,组织血流仪测量胰组织血流 ,放免法检测血浆二十碳烯酸代谢物等。结果 正常大鼠胰SSTR水平为 110± 5 8fmol/mg膜蛋白 ;ANP发病后 3、6、12h ,胰SSTR显著减低 ,SSTR2mRNA原位杂交信号显著减弱 ,胰组织血流明显降低 ,血栓素B2 显著增高 ;奥曲肽给药组胰组织血流降低和二十碳烯酸异常代谢显著矫正 ,病理损害减轻。结论 急性坏死性胰腺炎时胰组织SSTR表达显著降低。因此 ,生长抑素类似剂治疗ANP的机制可能主要与矫正二十碳烯酸异常代谢、改善胰组织微循环等有关 。

Objective Changes of somamtostatin receptor (SSTR) of pancreas, pancreatic blood flow and its relationship to metabolism of eicosanoids were investigated in order to elucidate the effectiveness of octreotide, an analogue of somatostatin, in acute necrotizng pancreatitis (ANP). Methods Rats with ANP were triggered with sodium taurocholate via pancreatobillary duct; SSTR was detected by radioligand binding assay (RBA) with 125 I somatostatiin 14; in Situ hybridization was employed in analysis of SSTR2 mRNA of pancreas; pancreatic blood flow was determined with tissue blood flowmeter and metabolites of eicosanoids were analyzed with radioimmunoassay. Results The level of SSTR of pancreas was 110±58 fmol/mg.protein in normal rats. Significant decrease of SSTR was shown at 3, 6, 12 hours after onset of ANP and of the signals of SSTR2 mRNA by in situ hybridization as well. Pancreatic blood flow was reduced while thromboxin 2 was increased significantly in the course of ANP. But in the group of ANP treated with octreotide, both the decrease of pancreatic blood flow and abnormal metabolism of eicosanoids were corrected, and the pathologic damages were reduced. Conclusion SSTR of pancreas is significantly reduced in ANP. Therefore, correction of abnormal metabolism of eicosanoids and improvement of pancreatic microcirculation may be the major mechanism of somatostatin analogues in treatment of ANP while inhibition of pancreatic enzymes via receptors may play a minor role.