Cool Johanna C, Dyer Jodie L, Xian Cory J, Butler Ross N, Geier Mark S, Howarth Gordon S
Cooperative Research Centre for Tissue Growth and Repair, Australia.
Growth Horm IGF Res. 2005 Feb;15(1):72-82. doi: 10.1016/j.ghir.2004.12.002. Epub 2005 Jan 21.
Insulin-like growth factor-I (IGF-I) has been demonstrated to enhance mucosal repair following intestinal damage induced by chemotherapeutic agents (intestinal mucositis). However, the potential for prophylactic IGF-I to protect the intestine remains undefined. We investigated the effects of IGF-I pre-treatment on chemotherapy-induced mucositis in rats. Male Sprague Dawley rats were treated for 7 days with 0 or 4.3mg/kg/day IGF-I delivered systemically via osmotic mini-pump. Rats received an intraperitoneal injection of 0 or 150 mg/kg 5-fluorouracil (5-FU) on day 7 and were killed 48 h later for assessment of intestinal damage and repair. Compared to normal controls, 5-FU decreased epithelial proliferation by 86%, concurrently increasing the incidence of apoptosis 87-fold, whilst decreasing small intestinal (SI) length by 14%, SI weight by 30% and total gut weight by 24%. 5-FU decreased villus height in the duodenum (23%), jejunum (20%) and ileum (30%) with crypt depths decreased by 31%, 27% and 33% in these gut regions. These effects were less profound in IGF-I pre-treated rats in which apoptosis was increased 48-fold, with SI length decreased by 7%, SI weight by 18% and total gut weight by 15% accompanied by decreases in villus height of 8% (duodenum), 14% (jejunum) and 21% (ileum), and crypt depth decreases of 23%, 16% and 17% for the same gut regions, compared to normal controls. We conclude that IGF-I pre-treatment only partially attenuates features of intestinal mucositis when assessed 48 h after 5-FU chemotherapy.
胰岛素样生长因子-I（IGF-I）已被证明可增强化疗药物诱导的肠道损伤（肠黏膜炎）后的黏膜修复。然而，预防性使用IGF-I保护肠道的潜力仍不明确。我们研究了IGF-I预处理对大鼠化疗诱导的黏膜炎的影响。雄性Sprague Dawley大鼠通过渗透微型泵以0或4.3mg/kg/天的剂量全身给予IGF-I，持续7天。在第7天，大鼠腹腔注射0或150mg/kg的5-氟尿嘧啶（5-FU），并在48小时后处死，以评估肠道损伤和修复情况。与正常对照组相比，5-FU使上皮细胞增殖减少86%，同时使细胞凋亡发生率增加87倍，而小肠（SI）长度减少14%，SI重量减少30%，总肠道重量减少24%。5-FU使十二指肠（23%）、空肠（20%）和回肠（30%）的绒毛高度降低，这些肠道区域的隐窝深度分别降低31%、27%和33%。在IGF-I预处理的大鼠中，这些影响不那么明显，与正常对照组相比，细胞凋亡增加48倍，SI长度减少7%，SI重量减少18%，总肠道重量减少15%，同时十二指肠（8%）、空肠（14%）和回肠（21%）的绒毛高度降低，相同肠道区域的隐窝深度分别降低23%、16%和17%。我们得出结论，在5-FU化疗后48小时进行评估时，IGF-I预处理仅部分减轻肠黏膜炎的特征。
