Morris J B, Guerrero N H, Furth E E, Stellato T A
Department of Surgery, Hospital of the University of Pennsylvania, Philadelphia 19104-4283.
Am J Surg. 1993 Jun;165(6):676-80. doi: 10.1016/s0002-9610(05)80786-x.
Pancreatic-derived proteases play a central role in the pathogenesis of ischemic intestinal injury. We postulated that exocrine blockade by pretreatment with a long-acting somatostatin analogue, octreotide acetate, would attenuate ischemic mucosal injury. Sprague-Dawley rats received subcutaneous octreotide (10 micrograms/kg/d) for 6 days by means of surgically implanted infusion ports. In a group of sham control rats, splanchnic blood flow (portal vein Doppler measurement) and duodenal trypsin activity (p-toluene sulfonyl-L-arginine methyl ester assay) were determined. In a separate experiment, pretreated animals were subjected to 60 minutes of superior mesenteric artery ischemia alone or followed by 30 minutes of reperfusion. Gross extent of hemorrhagic necrosis and microscopic injury (rank analysis) were assessed by a blinded observer. Pretreatment with octreotide reduced intraluminal duodenal trypsin activity by 46% without affecting portal blood flow. However, octreotide pretreatment significantly attenuated the microscopic depth of injury during ischemia and the extent of gross injury during reperfusion. It appears that somatostatin may have an adjuvant role in the prevention or progression of intestinal ischemic injury.
胰腺源性蛋白酶在缺血性肠损伤的发病机制中起核心作用。我们推测，通过长效生长抑素类似物醋酸奥曲肽预处理进行外分泌阻断，可减轻缺血性黏膜损伤。通过手术植入的输注端口，给予Sprague-Dawley大鼠皮下注射奥曲肽（10微克/千克/天），持续6天。在一组假手术对照大鼠中，测定内脏血流量（门静脉多普勒测量）和十二指肠胰蛋白酶活性（对甲苯磺酰-L-精氨酸甲酯测定）。在另一项实验中，对预处理的动物进行单独60分钟的肠系膜上动脉缺血或随后30分钟的再灌注。由一位不知情的观察者评估出血性坏死的大体范围和微观损伤（等级分析）。奥曲肽预处理使十二指肠腔内胰蛋白酶活性降低了46%，而不影响门静脉血流。然而，奥曲肽预处理显著减轻了缺血期间微观损伤的深度和再灌注期间大体损伤的程度。看来生长抑素在预防或减轻肠缺血性损伤方面可能具有辅助作用。
