Scopa C D, Koureleas S, Tsamandas A C, Spiliopoulou I, Alexandrides T, Filos K S, Vagianos C E
Department of Pathology, University of Patras, School of Medicine, Greece.
J Am Coll Surg. 2000 Apr;190(4):423-31. doi: 10.1016/s1072-7515(99)00285-9.
This study was undertaken to investigate the effect of growth hormone (GH) and insulin-like growth factor I (IGF-I), two well-known growth factors, on bacterial translocation, endotoxemia, enterocyte apoptosis, and intestinal and liver histology in a model of experimental obstructive jaundice in rats.
One hundred six male Wistar rats were divided into five groups: I (n = 21), controls; II (n = 22), sham operated; III (n = 22), bile duct ligation (BDL); IV (n = 21), BDL and GH treatment; and V (n = 20), BDL and IGF-I administration. By the end of the experiment, on day 10, blood bilirubin was determined, and mesenteric lymph nodes, liver specimens, and bile from the bile duct stump were cultured. Endotoxin was measured in portal and aortic blood. Tissue samples from the terminal ileum and liver were examined histologically and apoptotic body count (ABC) in intestinal mucosa was evaluated. Mucosal DNA and protein content were also determined.
Bilirubin increased significantly after BDL (p < 0.001). Bile from the bile duct was sterile. In group III, MLN and liver specimens were contaminated by gut origin bacteria (significant versus group I and II, p < 0.001, respectively). GH reduced significantly positive cultures (p < 0.01), and IGF-I had no effect. BDL resulted in significant increase in portal and aortic endotoxemia (p < 0.001); treatment with GH and IGF-I reduced it (p < 0.001). Mucosal DNA and protein content were reduced in animals with BDL and after treatment with GH or IGF-I; an increase to almost normal levels was noted in DNA, but not in protein. Overall the ileal architecture remained intact in all animal groups. The ABC increased after BDL. After GH and IGF-I administration, the ABC decreased significantly, and there was no difference between GH and IGF-I treated animals. After BDL, liver biopsies displayed typical changes of biliary obstruction, which were significantly improved after administration of GH and IGF-I.
Treatment with GH and IGF-I in rats with experimental obstructive jaundice reduces endotoxemia, and it improves liver histology. Apoptosis, in the intestinal epithelium, may serve as a morphologic marker of the ileal mucosal integrity, demonstrating the proliferative potential of GH and IGF-I in cases of obstructive jaundice, and this might be of potential value in patients with such conditions.
本研究旨在探讨生长激素（GH）和胰岛素样生长因子I（IGF-I）这两种著名的生长因子对大鼠实验性梗阻性黄疸模型中细菌移位、内毒素血症、肠上皮细胞凋亡以及肠道和肝脏组织学的影响。
106只雄性Wistar大鼠分为五组：I组（n = 21）为对照组；II组（n = 22）为假手术组；III组（n = 22）为胆管结扎（BDL）组；IV组（n = 21）为BDL + GH治疗组；V组（n = 20）为BDL + IGF-I给药组。实验结束时，即第10天，测定血胆红素，培养肠系膜淋巴结、肝脏标本及胆管残端胆汁。检测门静脉和主动脉血中的内毒素。对回肠末端和肝脏的组织样本进行组织学检查，并评估肠黏膜中的凋亡小体计数（ABC）。还测定了黏膜DNA和蛋白质含量。
BDL后胆红素显著升高（p < 0.001）。胆管胆汁无菌。III组中，肠系膜淋巴结和肝脏标本被源自肠道的细菌污染（与I组和II组相比有显著差异，分别为p < 0.001）。GH显著降低了阳性培养率（p < 0.01），而IGF-I无作用。BDL导致门静脉和主动脉内毒素血症显著增加（p < 0.001）；GH和IGF-I治疗可降低内毒素血症（p < 0.001）。BDL动物以及GH或IGF-I治疗后，黏膜DNA和蛋白质含量降低；DNA含量增加至几乎正常水平，但蛋白质含量未增加。总体而言，所有动物组的回肠结构均保持完整。BDL后ABC增加。给予GH和IGF-I后，ABC显著降低，且GH和IGF-I治疗的动物之间无差异。BDL后，肝活检显示典型的胆道梗阻变化，给予GH和IGF-I后显著改善。
在实验性梗阻性黄疸大鼠中，GH和IGF-I治疗可降低内毒素血症，并改善肝脏组织学。肠上皮细胞凋亡可能作为回肠黏膜完整性的形态学标志物，表明GH和IGF-I在梗阻性黄疸病例中的增殖潜力，这可能对此类患者具有潜在价值。
