^(125)I标记碱性成纤维细胞生长因子脑脊液途径用药在豚鼠耳蜗分布及影响

Distribution of basic fibroblast growth factor in inner ear of guinea pigs injected by different drug-approaches

目的探讨碱性成纤维细胞生长因子(basicfibroblastgrowthfactor,bFGF)进入内耳的途径及其在病理条件下对耳蜗及神经组织的保护作用机制。方法将125I标记bFGF(125IbFGF)采取侧脑室给药途径及生理和病理条件下肌肉给药途径注入豚鼠体内,测量相关组织γ放射计数率及耳蜗放射性自显影,观察125IbFGF在耳蜗分布及代谢情况。结果生理和病理条件下,豚鼠肌肉注射125IbFGF后血液和肝脏组织中γ放射性计数率明显高于本底,而脑组织、耳蜗和外淋巴γ放射性计数率与本底比较,变化不明显,耳蜗放射性自显影未见显影颗粒;侧脑室注入125IbFGF30min时,豚鼠血液、肝脏、脑组织、耳蜗及外淋巴γ放射性计数率均已增高,耳蜗放射自显影出现显影颗粒,脑及耳蜗组织γ计数率以2h和4h最高,8h明显下降,耳蜗放射性自显影仍可见显影颗粒,12hγ计数结果仍然高于本底,但耳蜗放射性自显影无明显显影颗粒,24h各脏器γ计数率接近本底;脑组织、耳蜗及血液γ放射性计数率始终保持平行变化。结论生理情况下,bFGF肌肉注射难以通过血脑屏障和血迷路屏障,而bFGF侧脑室注入后可迅速通过脑脊液与内耳之间的交通径路进入内耳,分布于外淋巴中,且在耳蜗内潴留时间较长;病理情况下如急性缺氧、氨基甙类抗生素耳中毒时。

Objective To investigate the approach of basic fibroblast growth factor(bFGF) entering inner ear, as well as its the protective mechanism to inner ear and nerve tissue in pathological situation. Methods ~125 I-bFGF was injected into guinea pigs body via the lateral ventricle and muscle under physical situation as well as pathological situation. Then the per minute γ-radioactive in blood, liver, thyroid gland, brain, cochlear and perilymph fluid was counted, and the distribution and metabolism of bFGF in the inner ear and autoradiography of the cochlea were also observed. Results γ-radioactive cpm of blood and liver increased significantly, while it did not change in brain, cochlea and perilymph after ~125 I-bFGF intramuscular injections. γ-radioactive cpm in blood, liver, brain, perilymph and cochlea had increased and autoradiography granules was found in the cochlea in 30 min after ~125 I-bFGF injected into CSF. In brain, perilymph and cochlea, a maximal value of γ-radioactive cpm was obtained between 2 h and 4 h, while that in 8 h decreased significantly. Autoradiography granules still were seen in 8 h. γ-radioactive cpm in 12 h was still higher than that in control group, but autoradiography granules can′t be seen. The result in 24 h was similar to that in control group. The time course of cpm in the blood, cochlea and perilymph always parallel changed. Conclusions bFGF has some difficulties in getting across blood-labyrinth barrier (BLB) and blood-brain barrier (BBB) under physical and pathological situation, such as acute anoxia, aminoglycoside-induced deafness. bFGF can reach inner ear, perilymph fluid, brain tissue and blood rapidly when it is injected into CSF and excreted slowly in those tissues. Permeability of BBB and BLB to bFGF is similar and has orientation.