粉防己碱对急性胰腺炎大鼠血清灌注的离体大鼠胃的保护作用及其机制

Protective role of tetrandrine in isolated rat stomachs perfused by serum from rats with acute pancreatitis

目的:研究急性胰腺炎(AP)大鼠血清对带血管灌流的离体大鼠胃内、外分泌功能的影响以及粉防己碱(Tet)的干预作用及其机制。方法:采用大鼠胆胰管逆行注射3%去氧胆酸钠复制AP模型,造模后5 h取动物血清。制备带血管灌流的离体大鼠胃,经胃动脉输注AP血清,并用Tet干预。从门静脉收集流出液,检测其中胃泌素、生长抑素、白细胞介素6(IL-6)及细胞因子诱导的中性粒细胞趋化因子1(CINC-1)水平的变化。同时从食管下段经贲门插管灌注生理盐水,从幽门收集流出液检测其中胃蛋白酶及胃酸分泌的变化。结果:AP大鼠胰腺组织破坏严重,胃壁出现多处糜烂、出血和溃疡,血清淀粉酶活性明显升高。用此AP血清灌流可引起离体胃胃泌素分泌增多,生长抑素分泌减少,IL-6和CINC-1分泌也增加,同时胃腔流出液中胃酸和胃蛋白酶含量增加。Tet可一定程度逆转AP血清刺激引起的胃泌素、胃酸和胃蛋白酶分泌的增多以及生长抑素分泌的抑制,减少炎症介质的释放(P<0.05),减轻胃黏膜损伤。结论:急性胰腺炎相关的胃损害与炎症血清有害成分的刺激有关。Tet可干预AP血清刺激所致的离体大鼠胃内、外分泌功能的改变,从而发挥对胃的保护作用。

AIM：To investigate the effects of the serum from rats with acute pancreatitis（AP） and tetrandrine on endocrinal and exocrinal functions of isolated rat stomachs. METHODS：Acute pancreatitis was induced in Sprague-Dawley rats by the method of retrograde bilio pancreatic duct injection with 3% sodium deoxycholate. The rat serum was collected 5 h after induction of AP, and used as an irritant to perfuse rat stomach. Endocrinal functions of the isolated rat stomachs were investigated by detecting gastrin and somatostatin in venous effluent, and exocrinal functions of the isolated rat stomachs were investigated by measuring pepsin and acid output in gastric lumen effluent. The releases of the cytokines and chemokines in venous effluent of the isolated rat stomachs were also examined. RESULTS：After induction of AP in the rats, the pancreatic tissue was damaged seriously, and obvious mucosal erosion and hemorrhages were also demonstrated in the stomach. The serum amylase level increased as well. The perfusion with AP rat serum caused significant increase in the levels of gastrin and inflammatory mediators, and decrease in the level of somatostatin in the venous effluent, and increase in the levels of pepsin and H＋ in the gastric lumen effluent. Tetrandrine reversed the serum-induced changes, including the changes of the gastric morphology in certain degree. CONCLUSION：Toxic substances in AP serum induce injury to the endocrinal and exocrinal functions of the isolated rat stomachs. The gastroprotective and anti-inflammatory effects of tetrandrine indicates therapeutic potential for acute gastrointestinal mucosal lesions in acute pancreatitis.