[Protective and rescue effects of transgenic bFGF/GFP expression mediated by cationic liposome on gentamicin-induced guinea pig cochlear toxicity].
OBJECTIVE
To observe the expression of cationic stearylamine (SA) liposome mediated basic fibroblast growth factor/green fluorescence protein (bFGF/GFP) gene in the cochlea of guinea pig, and evaluate the protection and rescue action of bFGF against the damage caused by gentamicin.


METHODS
Thirty-six guinea pigs were divided into 3 experimental groups. Prevention group with inoculation of SA-bFGF/GFP complexes through the round window of right ear and injection of gentamicin 150 mg.kg(-1).d(-1) one day after for 8 days and rescue group with injection of gentamicin for 8 days and infusion of SA-bFGF/GFP complexes in the same way on the ninth day, and control group with only injection of gentamicin for 8 days. Auditory brainstem responses (ABR) was measured prior to and after the administration and before the animals were killed respectively. The animals were killed after the experiment and ABR test, and specimens and slices of chochleae were made to examine the absence of outer and inner hair cells. The expression of GFP in cochlea shown by green fluorescence was observed with fluorescent microscopy.


RESULTS
Fluorescent microscopy showed green fluorescence in the cochleae of guinea pigs in prevention and rescue groups. There was no significant difference in ABR threshold between the left and right ears of animals in each group before and after experiment, among both ears of animals in the 3 groups before experiment, and between prevention and rescue group groups before killing (all P > 0.05). However, the ABR thresholds in prevention group and rescue group were significantly lower than that in control group before the animals were killed (P < 0.01 and P < 0.05). The average number of lost outer hair cells was 5 106 +/- 299 cells and 5 605 +/- 109 cells in prevention group and rescue group respectively, without a significant difference between them (P > 0.05). The average amount of missing inner hair cells was 301 +/- 64 cells and 487 +/- 92 cells in prevention group and rescue group respectively, without a significant difference between them (P > 0.05), and significantly lower than that in control group (1 062 +/- 67, P < 0.01 and P < 0.05). The average amount of missing outer hair cells in control group was 6 248 +/- 119 cells, significantly higher than that in prevention group (5 106 +/- 299, P < 0.01) and that in rescue group (5 605 +/- 109, P < 0.05).


CONCLUSIONS
SA-liposome mediated bFGF/GFP gene, which was perfused in one ear, can be expressed highly in both cochleae of the guinea pig, and may protect and rescue cochlea against gentamicin ototoxicity.
Yin
Jinshu
J
Department of Otorhinolaryngology, Railway General Hospital, Beijing 100038, China.
Zhai
Suoqiang
S
Guo
Wei
W
Hu
Yinyan
Y
Shi
Li
L
D000588:Amines / Q000008:administration & dosage / Q000737:chemistry; D000818:Animals; D030801:Animals, Genetically Modified; D000900:Anti-Bacterial Agents / Q000633:toxicity; D003051:Cochlea / Q000378:metabolism / Q000473:pathology; D015834:Cochlear Diseases / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics* / Q000502:physiology; D015870:Gene Expression; D005839:Gentamicins / Q000633:toxicity; D049452:Green Fluorescent Proteins; D006168:Guinea Pigs; D008081:Liposomes / Q000008:administration & dosage / Q000737:chemistry; D008164:Luminescent Proteins / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage / Q000235:genetics
D000588:Amines; D000900:Anti-Bacterial Agents; D005839:Gentamicins; D008081:Liposomes; D008164:Luminescent Proteins; D011993:Recombinant Fusion Proteins; C115688:sterylamine; D016222:Fibroblast Growth Factor 2; D049452:Green Fluorescent Proteins