Pillai S B, Hinman C E, Luquette M H, Nowicki P T, Besner G E
Department of Surgery, The Ohio State University and Children's Hospital, Columbus, Ohio 43205, USA.
J Surg Res. 1999 Dec;87(2):225-31. doi: 10.1006/jsre.1999.5764.
We have shown previously that heparin-binding epidermal growth factor (EGF)-like growth factor (HB-EGF) is cytoprotective for intestinal epithelial cells exposed to hypoxia in vitro. We now examine the effects of HB-EGF on the recovery of small intestine from ischemic injury in vivo.
Segmental intestinal ischemia of 60-min duration was produced in adult rats by occlusion of a first-order branch of the superior mesenteric artery. Recombinant HB-EGF (100 microg) was injected intraluminally into the proximal small bowel after 45 min of ischemia in experimental animals, and buffered saline was injected in control animals. Animals were sacrificed after 48 h, and the affected bowel was resected, processed, and examined microscopically, with histologic grading of the ischemic injury. Additional animals were allowed to recover for up to 1 month to evaluate mortality differences.
Intraluminal administration of HB-EGF resulted in significantly decreased extent and severity of ischemia/reperfusion injury, with significantly decreased grade of injury in the HB-EGF-treated compared with nontreated animals (average injury grade 0.66 compared with 2.44, respectively). Moreover, the mortality rate was significantly lower in the HB-EGF-treated animals compared with nontreated animals (0% vs 25%, respectively). HB-EGF-treated animals had increased weight gain in the postischemia recovery period.
We conclude that HB-EGF, given intraluminally, reduces both the amount and the severity of ischemia/reperfusion injury in the small bowel, reduces the mortality associated with intestinal ischemia, and may enhance intestinal recovery. The in vitro and in vivo cytoprotective effects of this growth factor suggest that it may, in the future, be clinically useful in treating patients with intestinal ischemia.
我们之前已经表明，肝素结合表皮生长因子（EGF）样生长因子（HB-EGF）对体外暴露于缺氧环境的肠道上皮细胞具有细胞保护作用。我们现在研究HB-EGF对体内小肠缺血损伤恢复的影响。
通过阻断肠系膜上动脉的一级分支，在成年大鼠中造成持续60分钟的节段性肠缺血。在实验动物缺血45分钟后，将重组HB-EGF（100微克）腔内注射到近端小肠，对照动物注射缓冲盐水。48小时后处死动物，切除受影响的肠段，进行处理并进行显微镜检查，对缺血损伤进行组织学分级。另外让动物恢复长达1个月以评估死亡率差异。
腔内给予HB-EGF导致缺血/再灌注损伤的程度和严重程度显著降低，与未治疗动物相比，HB-EGF治疗组的损伤分级显著降低（平均损伤分级分别为0.66和2.44）。此外，与未治疗动物相比，HB-EGF治疗组的死亡率显著降低（分别为0%和25%）。HB-EGF治疗组动物在缺血后恢复期体重增加。
我们得出结论，腔内给予HB-EGF可减少小肠缺血/再灌注损伤的数量和严重程度，降低与肠缺血相关的死亡率，并可能促进肠道恢复。这种生长因子的体外和体内细胞保护作用表明，它未来可能在临床上用于治疗肠缺血患者。
