Bloechle C, Kusterer K, Konrad T, Hosch S B, Izbicki J R, Knoefel W T, Broelsch C E, Usadel K H
Abteilung für Allgemeinchirurgie, Universitäts-Krankenhaus Eppendorf, Universität Hamburg, Germany.
Horm Metab Res. 1994 Jun;26(6):270-5. doi: 10.1055/s-2007-1001682.
Changes in glucose metabolism mediated by natural somatostatin and two derivatives (octreotide, 008) were studied in hypoxic ischemic cell injury of the isolated perfused rat liver. The tested somatostatin and its analogues were previously shown to exert protective actions in liver damage induced by hypoxic ischemia and reperfusion. In isolated perfused livers of rats starved for 24 hours and unstarved rats flow rate was reduced and oxygen supply interrupted for 180 min. Then the livers were normoxically reperfused for 30 min. Glucose and lactate concentration, as well as LDH and GLDH activity, were determined in the effluent. In starved and unstarved rat livers hypoxic ischemia resulted in a substantial enzyme release. In livers harvested from unstarved rats hepatic glucose release was noticed which ceased towards prolonged low flow ischemia. In livers harvested from starved rats containing low hepatic glycogen concentration only minimal hepatic glucose release was present. In starved and unstarved rats pretreatment with somatostatin, octreotide, and 008 significantly reduced LDH and GLDH release (p < 0.001). In unstarved rats natural somatostatin and octreotide pretreatment resulted in a substantial output of glucose during the hypoxic ischemic perfusion period (p < 0.001), whereas livers with 008 pretreatment did not show any difference in glucose release compared to controls. In livers harvested from starved rats neither somatostatin nor octreotide nor 008 pretreatment led to a difference in glucose output observed in controls. Natural somatostatin and octreotide cause a strong hepatic glucose release even under hypoxic ischemic conditions in rat livers with filled glycogen stores. The protective action of natural somatostatin, octreotide, and 008 is not mediated by changes in glucose metabolism, and is not related to endocrine activity.
在离体灌注大鼠肝脏的缺氧缺血性细胞损伤中，研究了天然生长抑素及其两种衍生物（奥曲肽、008）介导的葡萄糖代谢变化。先前已表明，所测试的生长抑素及其类似物在缺氧缺血和再灌注诱导的肝损伤中发挥保护作用。在饥饿24小时的大鼠和未饥饿大鼠的离体灌注肝脏中，降低流速并中断氧气供应180分钟。然后将肝脏在常氧条件下再灌注30分钟。测定流出液中的葡萄糖和乳酸浓度以及乳酸脱氢酶（LDH）和谷氨酸脱氢酶（GLDH）活性。在饥饿和未饥饿的大鼠肝脏中，缺氧缺血导致大量酶释放。在未饥饿大鼠的肝脏中，观察到肝葡萄糖释放，而在长时间低流量缺血时停止。在糖原浓度低的饥饿大鼠肝脏中，仅存在极少的肝葡萄糖释放。在饥饿和未饥饿的大鼠中，用生长抑素、奥曲肽和008预处理可显著降低LDH和GLDH释放（p<0.001）。在未饥饿的大鼠中，天然生长抑素和奥曲肽预处理导致缺氧缺血灌注期间葡萄糖大量输出（p<0.001），而用008预处理的肝脏与对照组相比，葡萄糖释放没有差异。在饥饿大鼠的肝脏中，生长抑素、奥曲肽和008预处理均未导致与对照组观察到的葡萄糖输出差异。即使在糖原储备充足的大鼠肝脏缺氧缺血条件下，天然生长抑素和奥曲肽也会引起强烈的肝葡萄糖释放。天然生长抑素、奥曲肽和008的保护作用不是由葡萄糖代谢变化介导的，也与内分泌活性无关。
