胶质细胞来源的神经营养因子对螺旋神经节神经元耳毒性损伤的保护作用

目的评价胶质细胞来源的神经营养因子(glial cell line-derived neurotrophic factor,GDNF)对耳毒性药物损伤豚鼠螺旋神经节神经元(spiral ganglion neuron,SGN)的保护作用。方法单剂量联合应用卡那霉素(kanamycin,KM)和利尿酸(ethacrynic acid,EA)致聋豚鼠,用药后21 d经微渗透压泵左耳鼓阶内连续灌注GDNF 26d,光镜下观察Corti器和SGN形态学变化,定量分析正常听力、用药后21 d、GDNF、GDNF组对侧耳和用药后47 d各组SGN细胞密度和细胞直径。结果系统性联合应用KM和EA可以导致耳蜗毛细胞严重和彻底的丢失,继发SGN进行性变性。GDNF组SGN形态与正常听力组比较无明显差别;细胞密度小于正常听力组,与用药后21 d组比较无显著性差异,大于GDNF组对侧耳和用药后47 d组;细胞直径比正常听力组小,但较其他组大。结论耳蜗内长期灌注GDNF对豚鼠耳毒性药物损伤后残余的SGN有保护作用,避免细胞进一步丢失,对损伤细胞可能有修复功能。

Protective Role of Glial Cell Line-Derived Neurotrophic Factor Following Ototoxic

Objective To evaluate the protective effect of glial cell line-derived neurotrophic factor(GDNF) on guinea pig spiral ganglion neurons(SGNs) after ototoxic damage.Methods Guinea pigs were deafened by systematically application of kanamycin(KM) and ethacrynic acid(EA).21 days post KM and EA administration,GDNF was infused daily for 26 days via microcannula-osmotic pump to the scala tympani of the left ear of the animal.The morphological changes of Corti's organ and SGN were observed under light microscope.Neuron density and cell diameter were measured and analysed.Results Some hair cells were severely and some were completely lost.Auditory nerves and SGNs were gradually degenerated secondary to the loss of hair cells.The morphology of SGNs in GDNF group was similar to the normal animal.Neuron density in GDNF group was lower than that in the normal group,the same as that in 21 days post KM and EA administration group,and significantly higher than both in GDNF untreated right ear and 47 days post KM and EA administration group.Cell diameter in GDNF group was shorter than that in normal group and longer than those in other groups.Conclusion Chronic intracochlear infusion of GDNF has protective effect on the SGN survival.It can prevent the further damage neurons and may act a role in repairing.