D-半乳糖对神经元和成纤维细胞拟老化作用的实验研究

STUDIES ON CELL SENESCENCE INDUCED BY D GALACTOSE IN CULTURED NEURONS AND FIBROBLASTS

实验用体内、外相结合的方法，观察了Ｄ－半乳糖（Ｄ－ｇａｌａｃｔｏｓｅ，Ｄ－ｇａｌ．）对细胞的促老化作用。结果表明，Ｄ－ｇａｌ使培养大鼠胎脑神经元出现生长发育缓慢、突起脱落、死亡率增高等退行性变；大鼠肺成纤维细胞的体外分裂代数减少；人胎儿肺二倍体成纤维细胞（ＨＢＳ）分裂周期中Ｇ２－Ｍ期细胞减少、Ｇ－Ｇ１期细胞增加、ＤＮＡ含量下降，细胞增殖速度减慢；大鼠胎脑神经细胞和ＨＢＳ中ＳＯＤ含量降低，丙二醛（ＭＤＡ）水平升高，这些结果与次黄瞟呤（ＨＰＸ）－黄瞟呤氧化酶（ＸＯＤ）系统产生的超氧阴离子自由基（Ｏ－２·）作用一致。提示，Ｄ－ｇａｌ抑制细胞生长发育和分裂繁殖，加速细胞老化，其机理可能与Ｏ－２·等活性氧（ＲＯＳ）过荷引起的脂质过氧化有关。

The cell senescence induced by D galactose(D gal) in cultured rat fetal brain neurons and human fetal lung fibroblast was investigated in vivo and in vitro. The results showed pronounced decreases in nerve cell diameters, number of process and percentage of multiprocess neurons including'pyramidal'and 'stellate' shaped and a rather high level of mortality rate observed in D gal treated (8g/L) neurons. Lessening of the proliferating population of lung fibroblast taken from rat treated with D gal(50mg/kg·d, subcutanous injection for 6 weeks) was observed. We have also determined the changes of cell cycle in human fetal lung fibroblast cells treated with D gal (8g/L): the proportion of the G o G 1 cells increased but the G 2 M and DNA level and the results showed that decreased and the cell growth rate declined in comparison with those of the control. Lipid peroxidation was observed in both kinds of cells because D gal was proved to have action of decreasing SOD activity and increasing MDA content, the results found in D gal treated rats were similar to those observed in hypoxanthine xanthine oxidation reaction system(O - 2· ), indicating that reactive oxygen was generated in the course of D gal metabolism. It is concluded that D gal has the hastening effect on cell senescence and oxidative stress might be responsible for this aging effect.