Kling Pamela J, Taing K Muy, Dvorak Bohuslav, Woodward Suann S, Philipps Anthony F
Department of Pediatrics, Steele Memorial, Children's Research Center, The University of Arizona Health Sciences Center, Tucson, AZ 85724, USA.
Growth Factors. 2006 Sep;24(3):218-23. doi: 10.1080/08977190600783162.
Insulin-like growth factors I and II (IGF-I and IGF-II) are potent growth factors involved in development. IGF-I stimulates proliferation of erythropoietic progenitors and parenteral IGF-I administration stimulates in vivo erythropoiesis in animals. IGF-I and IGF-II are both present in mammalian milks and when milk-borne, are resistant to neonatal gastrointestinal degradation. Whether milk-borne IGF-I or IGF-II regulates neonatal erythropoiesis in not known. We hypothesized that physiological doses of enteral IGFs stimulate erythropoiesis in suckling rats.
Eight day-old Sprague Dawley rats were artificially fed for 4 days with rat milk substitute (RMS) or RMS supplemented with physiological levels of IGF-I or IGF-II. Rats fed IGF-I and IGF-II were compared to control RMS. Blood and marrow were collected; measures of red cell mass, measures of erythropoietic stimulus, and indices of iron status were measured.
Rats fed IGF-I had higher hemoglobin (Hb) levels (100 +/- 10 g/l), compared to those fed RMS (94 +/- 9) or IGF-II (91 +/- 6), p < 0.001. After IGF-I supplementation, red blood cell counts (RBC) (p < 0.04) and hematocrits (p < 0.002) were also higher. Plasma erythropoietin (Epo) levels, reticulocytes, plasma iron and erythrocyte iron incorporation were similar.
Intact enteral IGF-I reaches distal erythropoietic tissue resulting in greater red cell mass, but not by increasing plasma Epo levels or by altering cellular iron transport.
胰岛素样生长因子I和II(IGF-I和IGF-II)是参与发育的强效生长因子。IGF-I刺激红细胞生成祖细胞的增殖,肠外给予IGF-I可刺激动物体内的红细胞生成。IGF-I和IGF-II都存在于哺乳动物乳汁中,且经乳汁传递时,对新生儿胃肠道降解具有抗性。乳汁中的IGF-I或IGF-II是否调节新生儿红细胞生成尚不清楚。我们推测生理剂量的肠内IGF可刺激哺乳大鼠的红细胞生成。
用大鼠代乳品(RMS)或补充了生理水平IGF-I或IGF-II的RMS人工喂养8日龄的斯普拉格-道利大鼠4天。将喂食IGF-I和IGF-II的大鼠与对照组RMS进行比较。采集血液和骨髓;测量红细胞质量、红细胞生成刺激指标和铁状态指标。
与喂食RMS(94±9)或IGF-II(91±6)的大鼠相比,喂食IGF-I的大鼠血红蛋白(Hb)水平更高(100±10 g/l),p<0.001。补充IGF-I后,红细胞计数(RBC)(p<0.04)和血细胞比容(p<0.002)也更高。血浆促红细胞生成素(Epo)水平、网织红细胞、血浆铁和红细胞铁掺入情况相似。
完整的肠内IGF-I可到达远端红细胞生成组织,导致更大红细胞量,但并非通过提高血浆Epo水平或改变细胞铁转运来实现。