Kohno Y, Shiraki K, Mura T
Department of Pediatrics, Tottori University School of Medicine, Yonago, Japan.
Pediatr Res. 1991 Mar;29(3):251-5. doi: 10.1203/00006450-199103000-00006.
We studied the effect of human milk on DNA synthesis of neonatal hepatocytes to elucidate the physiologic role of human milk in growth of the liver. Neonatal hepatocytes were isolated from 5-d-old rats and cultured in serum-free medium. Human milk stimulated DNA synthesis of these hepatocytes in a concentration-dependent manner. The stimulatory activity of 7.5% (vol/vol) human milk plus 0.1 mumol/L insulin was five times that of control and was almost the same as that of 20 micrograms/L human epidermal growth factor (hEGF) plus insulin. The effect of human milk was additive with treatment with hEGF and insulin. The milk associated with prolonged jaundice of infants was significantly more active than the milk that was not associated with jaundice, although the concentration of hEGF was not different between the two types of milk. The mitogenic activity of milk was heat-labile, inactivated by DTT and stable after treatment with trypsin. Three peaks of the activity were detected in milk by gel filtration and the fraction containing proteins of molecular weight between 36,000 and 76,000 showed the highest activity. Anti-hEGF antibody did not inhibit this activity completely. These results suggested the presence of mitogens other than hEGF or a more active form of hEGF in human milk. The milk associated with breast-milk jaundice exerts a different influence on cell growth and may affect maturation of the liver function related to bilirubin metabolism. The mitogenic activity of milk might be important for growth and development of the liver in infants.
我们研究了人乳对新生大鼠肝细胞DNA合成的影响，以阐明人乳在肝脏生长中的生理作用。从5日龄大鼠分离出新生肝细胞，并在无血清培养基中培养。人乳以浓度依赖的方式刺激这些肝细胞的DNA合成。7.5%（体积/体积）人乳加0.1μmol/L胰岛素的刺激活性是对照组的5倍，几乎与20μg/L人表皮生长因子（hEGF）加胰岛素的刺激活性相同。人乳的作用与hEGF和胰岛素联合处理具有相加性。与婴儿长时间黄疸相关的乳汁比与黄疸无关的乳汁活性明显更高，尽管两种乳汁中hEGF的浓度没有差异。乳汁的促有丝分裂活性对热不稳定，可被二硫苏糖醇（DTT）灭活，用胰蛋白酶处理后稳定。通过凝胶过滤在乳汁中检测到三个活性峰，含有分子量在36,000至76,000之间蛋白质的组分显示出最高活性。抗hEGF抗体不能完全抑制这种活性。这些结果表明人乳中存在除hEGF以外的有丝分裂原或更具活性形式的hEGF。与母乳性黄疸相关的乳汁对细胞生长产生不同影响，并可能影响与胆红素代谢相关的肝功能成熟。乳汁的促有丝分裂活性可能对婴儿肝脏的生长和发育很重要。
