人类重组酸性成纤维细胞生长因子对新生大鼠生长发育的影响

Effect of human recombinant acidic fibroblast growth factor on growth and development in new-born rats

目的:比较野生酸性成纤维细胞生长因子(waFGF)和其核转位序列(NLS)敲除后的重组aFGF(raFGF)对新生大鼠生长发育的影响,评价raFGF的有丝分裂活性及其相关的生物学特性。方法:实验用Wistar新生大鼠,观察waFGF、raFGF和suramin对其体重、外观、存活率和睁眼时间的影响。结果:体重时程的变化表明,suramin+raFGF组大鼠在生后16 d内体重明显低于suramin+waFGF组,但两组均明显低于正常组和空白对照组,且明显高于suramin组。suramin组和suramin+raFGF组幼鼠背部有皮屑现象,出现不同程度的角弓反张症状。suramin组幼鼠生后均未睁眼,在16 d内全部死亡;而正常组幼鼠、空白对照、suramin+waFGF和suramin+raFGF组幼鼠分别在出生后14、14、19和22 d睁眼,21 d其存活率分别为99.3%、87.6%、66.7%和20.0%,后两者比较差异有显著性(P<0.05)。结论:suramin作为aFGF的抑制剂,可抑制机体的生长发育,在一定程度上可被外源waFGF反转,但raFGF作用较弱。提示,aFGF经过基因敲除核转位序列后,对新生大鼠发育影响较小,可能与其促细胞分裂性降低有关。

Objective To evaluate the biological effect of recombinant acidic fibroblast growth factor （raFGF） with nuclear traslocation sequence （NLS） knocked-out through comparing the effects of waFGF, raFGF and suramin on growth and development in new-born rats. Methods Wistar new-born rats were divided into 5 groups, namely normal, blank, suramin, suramin＋waFGF （s＋w） and suramin＋raFGF （s＋ r）, respectively. The differences of body weight （BW）, outlook, survival rate and time of opening eyes in new-born rats were observed. Results The BW in s＋r group at 16 d after birth of rats was significantly lower than that in s＋w group. However, the BW in s＋r and s＋w groups were significantly lower than those in normal and blank groups. There were the desquamate symptoms in the back of new-born rats in suramin and s＋ r groups and the opisthotonos in suramin and s＋ r groups with different degrees. All the rats in suramin group had not opened their eyes till death at 16 d after birth. Innormal, blank, s＋w and s＋r groups, the times of opening eyes in new-born rats were 14, 4, 19 and 22 d after birth, respectively. Their survival rates were 99.3%, 87.6%, 66.7% and 20. 0%, respectively, within 22 d after birth, and there was a significant difference between s＋w and s＋r groups （P〈0. 05）. Conolusion Acting as the antagonist of aFGF, suramin can inhibit body＇s growth and development, this inhibition can be turned over by exogeneous aFGF to some extent, and raFGF has no such significant effect. It suggests that the aFGF with NLS knocked-out affects new-born rats slightly and may lie in its decreased mitogenic activity.