成纤维细胞生长因子4在阿糖胞苷所致拇指多指畸形鼠体内表达变化的研究

Expression of fibroblast growth factor 4 in cytarabine-induced polydactyly of thumb

目的 研究成纤维细胞生长因子4 （FGF-4）在阿糖胞苷所致的拇指多指畸形鼠的肢芽中表达的变化;探索多指畸形的形成机制.方法 运用腹腔注射阿糖胞苷的方法建立拇指多指畸形鼠的动物模型,选择不同给药时间的孕鼠（11.5 d、12.5d、13.5d、14.5 d）,采用整体原位杂交的方法检测胚胎鼠肢芽的间充质细胞中FGF-4的表达;采用HE染色及软骨染色的方法检测胚胎鼠骨骼及软组织的发育情况;对正常出生的畸形鼠进行X线摄片,以进一步确定骨骼发育的畸形变化.结果 在给药组所产生的鼠胚中,通过整体原位杂交方法检测,FGF4表达在给药组中11.5d、12.5d、13.5d和14.5d时FGF4表达的相对面积分别为22.21％、84.81％、58.43％和47.59％,而空白组中各天数的FGF4表达相对面积分别为6.74％、30.80％、19.64％和15.44％.FGF-4在肢芽的表达比正常组明显增多,其所分布的范围比对照组广,持续的时间比对照组长.HE染色和软骨染色发现拇指多指畸形鼠的肢体骨骼呈现多掌骨及多指骨的畸形变化.结论 FGF-4在阿糖胞苷所致的拇指多指畸形鼠的肢芽呈现高表达.

Objective To explore the expression and mechanisms of fibroblast growth factor 4 （FGF-4） in cytarabine-induced polydactyly of thumb.Methods An intraperitoneal injection of cytarabine was used to establish a rat model of polydactyl and syndactyl.For different periods of gestational rats （11.5,12.5,13.5,14.5 days）,whole mount in situ hybridization was used to detect the expression of FGF-4 in polydactyly.The stains of hematoxylin ＆amp; eosin and cartilage were used to detect the embryonic development of skeleton and tissues.And radiology was employed for detecting the aberration of skeleton.Results In test group,the expression of FGF-4 was up-regulated in limb bud and its expanded domain persisted longer than control group.In test group,the FGF4 expression relative areas at Days 11.5,12.5,13.5 and 14.5 were around 22.21%,84.81%,58.43% and 47.59% versus 6.74%,30.80%,19.64% and 15.44% respectively.Conclusions FGF-4 is up-regulated in cytarabine-induced limb bud of polydactyl embryos.