| INTRODUCTIONHeat shock proteins are a group of highly conserved proteins induced or increasingly expressed by a variety of physical, chemical and biologic injuries. They are important for tissue and cells against ischemia , hypoxia or cytotoxic drug, especially against oxidative injury. As a immanent self - preservation system, HSPs can lead to acquisition of more natural tolerance than with pharmacological approaches. A study has shown that upregulation of heat shock proteins protected the ear from acoustic injury. Considering the potent cytoprotective action of HSPs, nontoxic chaperone inducers may be of great therapeutic benefit as a new generation of drugs for the treatment of diseases. Salicylates have been among the most commonly used medications in the world. Because they could affect the auditory system, they were known as the ototoxic drugs. But recent studies have demonstrated that sodium sa-licylate could attenuated noise - or gentamicin - induced ototoxicity. Some studies have shown that sodium salicylate potentiated and induced the expression of HSP70. Because of the protective effect of HSP, we thought that sodium salicylate could induce HSP in rat cochleae. So this study was to study the induction of HSP70 in rat cochleae and to evaluate the effects of sodium salicylate on the protection to the injuries.MATERIALS AND METHODSMaterial: 57 healthy male Wistar rats with normal Preyer's reflexes weighting 220 - 260 g were divided into 6 groups of nine animals each at random and heat shock treatment as positive control group with three animals. 100mg/kgSS group: 100mg/kgSS, ip. 250mg/kgSS group:250 mg/kgSS,ip. 500mg/kgSS group:500 mg/kgSS,ip. Control group;the same amount of physiological saline, ip. 37 group: placed in an ambient environment of 37 for 30 min, recovered at room temperature. 100mg/kgSS - plus - 37 group: 100 mg/kgSS, ip, 60 min prior to their placement at 37 for 30 min, recovered at room temperature. Positive control group: placed in a 45.6 constant temperature water bath, after the core body temperature reached 42. 5 for 15 min, recovered at room temperature. Methods; (1) Measurement of auditory brainstem response ( ABR) : We determined the ABR thresholds before, 4 hours and 24 hours after administration of all kinds of drugs. Three animals of each group were anesthetized with 3% sodium pentobarbital 40mg/kg mtraperitoneally. Reference electrodes were placed subcutaneously below the ipsilateral pinna, active electrodes at the vertex, and ground electrodes at below the con-tralateral pinna. Stimuli were generated by a generator of Danac -7. ABR thresholds were recorded using click at 2KHz. The stimulator produced the stimulus sound beginning with 95 dB, and detected the P3 wave to confirm the ABR thresholds. (2) Immunohistochemical staining and image analyses: After 6 hours of the treatments, others were deeply anesthetized and systemically perfused through the heart with physiological saline, followed by 4% paraformaldehyde fixative.The cochleae were dissected from the temporal bones, and each cochleae was immersed in the same fixative for 24 hours at 4 . Subsequently the cochleae were rinsed in PBS, then decalcified for 7 days at room temperature. After Decalcification, the cochleae were cryopro-tected in a 30% sucrose/PBS solution at 4 overnight. Each cochleae was then infiltrated with OCT compound, and 5 - ujm cryostat sections were collected on gelatinsubbed slides. The sections were in 0. 5% H2O2 in PBS at room temperature, then incubated with A liquid and B liquid, and developed using DAB as the chromogen. Dehydration was performed in a graded ethanol. Then the slides were cover-slipped with resin. We used the image quantitative analysis technique to determine the optical density average of HSP70 immunoreactivity. The data were analyzed with the Dunnett t test and the SNK test.RESULTS1. The ABR auditory thresholds were transiently increased in 250mg/kg sodium salicylate group and 500mg/kg sodium salicylate group. The ABR auditory thresholds were s... |
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