Avni B, Haddad R, Kashtan H, Kaplan D, Graf E, Siegal A, Skornick Y, Kaplan O
Department of Surgery A and Biochemistry Laboratory, Tel-Aviv Medical Center, Israel.
Dig Dis Sci. 1998 Jan;43(1):193-202. doi: 10.1023/a:1018861112495.
The long-term effects of octreotide, the synthetic analog of the hormone somatostatin, on acute experimental pancreatitis were studied. Acute pancreatitis was induced in rats by intraparenchymal injections of 0.5 ml 5% or 10% sodium taurocholate. Octreotide (10 mg/kg/day, subcutaneously), or saline injections as controls, were started four hours later, and their effects were assessed 30, 60, and 90 days after the induction of pancreatitis. Neither intrapancreatic saline injections nor octreotide administration without the induction of pancreatitis caused any biochemical or histological abnormalities. Taurocholate-induced pancreatitis was followed by remarkable hyperglycemia, which was ameliorated by octreotide. Thirty days after induction of pancreatitis, glucose levels were 269+/-21 mg/100 ml and 153+/-17 mg/100 ml in the control and octreotide treated animals, respectively (P < 0.02). Octreotide administration was associated with increased pH values after 60 and 90 days (P < 0.05 for the 90 days group). The levels of hematocrit, calcium, and amylase were already within the normal ranges after 30 days and were unaffected by octreotide. There were no signs of chronic exocrine insufficiency and all the surviving rats gained weight during the follow-up. However, the relative weights of the pancreases of the octreotide-treated animals were higher than those of the controls 30 days after IOP. Histopathological evaluation demonstrated regeneration of the pancreatic tissue, and increased number and hypertrophy of the islets of Langherhans. There were no significant differences whether the octreotide treatment was given for only 48 or 96 hr. Survival was significantly improved by octreotide; only one octreotide-treated rat (2.5%) with 10% taurocholate-induced pancreatitis died, while six (15%) of the control animals succumbed (P < 0.05). These studies provided data on the sequelae of acute pancreatitis and showed that octreotide may have long-term beneficial effects in this disease.
研究了生长抑素的合成类似物奥曲肽对急性实验性胰腺炎的长期影响。通过实质内注射0.5 ml 5%或10%牛磺胆酸钠在大鼠中诱导急性胰腺炎。4小时后开始皮下注射奥曲肽(10 mg/kg/天)或生理盐水作为对照,并在胰腺炎诱导后30、60和90天评估其效果。胰腺内注射生理盐水或未诱导胰腺炎而给予奥曲肽均未引起任何生化或组织学异常。牛磺胆酸钠诱导的胰腺炎之后出现显著的高血糖,奥曲肽可改善这种情况。胰腺炎诱导30天后,对照组和奥曲肽治疗组动物的血糖水平分别为269±21 mg/100 ml和153±17 mg/100 ml(P<0.02)。奥曲肽给药在60天和90天后与pH值升高相关(90天组P<0.05)。红细胞压积、钙和淀粉酶水平在30天后已在正常范围内,且不受奥曲肽影响。没有慢性外分泌功能不全的迹象,所有存活大鼠在随访期间体重增加。然而,奥曲肽治疗组动物的胰腺相对重量在IOP后30天高于对照组。组织病理学评估显示胰腺组织再生,胰岛数量增加且肥大。奥曲肽治疗48小时或96小时均无显著差异。奥曲肽显著提高了存活率;10%牛磺胆酸钠诱导的胰腺炎中,仅1只接受奥曲肽治疗的大鼠(2.5%)死亡,而6只(15%)对照动物死亡(P<0.05)。这些研究提供了急性胰腺炎后遗症的数据,并表明奥曲肽在该疾病中可能具有长期有益作用。