| Research BackgroundWith the development of social industrialization,the probability of human exposure to noise is increasing.The epidemiological investigation shows that noise is the most common cause which caused occupational hearing damage and disability,noise has become the first of world's seven public nuisances.At present,the morbidity rate of noise induced hearing loss(noise-induced hearing loss,NIHL)is still growing,which is next only to presbycusis.Acute acoustic trauma(acute acoustic trauma,AAT)causes hearing damage,tinnitus and aural fullness during or after exposure to noise.AAT can be caused by exposure to steady-state noise or impulse noise.Steady-state noise usually generated by heavy equipment,and it is the most common steady-state noise in social environment.Impulse noise generated by stamping,forging hammer,explosion,guns etc.It lasts less than 0.5 second and intervals more than 1 second.sound pressure level of impulse noise increase rapidly,and do more harmful than that caused by steady-state noise.Noise not only do harm to human health,but also causes financial burden to society[1-5].Therefore,it is very important to reduce and prevent AAT.The mechanism of NIHL consist of mechanical and metabolic injury.It is consensus that metabolic injury following mechanical injury.Many studies have shown that AAT is related to oxidative damage,and reactive oxygen species(reactive oxygen species,ROS)plays a key role in oxidative damage.Changes of the cochlear oxidation state(Dynamic balance of production and elimination of ROS in cochlea under physiological conditions,but ROS increases dramatically under noise exposure),the reduction of cochlear blood flow(cochlear blood flow,CBF),the membrane damage of hair cells and the influence of free radicals(such as ROS,active nitrogen),changes of the cochlear oxidation state and the reduction of cochlear blood flow can induces the accumulation of ROS,ROS damages molecules such as DNA,induces gene mutation and mitochondrial damage,and results in hair cell dysfunction and hearing loss.Rhodiola is a traditional herb,which have pharmacological effects of anti-hypoxia,anti-oxidation,anti-fatigue,anti-aging[6-10].Salidroside is the most active component of rhodiola that extracted from roots and stems of Rhodiola rosea,salidroside is one of phenylpropanoid glycoside that protect cells through anti hypoxia and anti-oxidation.ObjectiveGuinea pigs were treated with Nuodikang Capsule(the component of Nuodikang Capsule is rhodiola)orally before noise exposure,antagonistic effect of Rhodiola on NIHL in guinea pigs was investgated.MethodsForty guinea pigs were randomly divided into four groups,10 guinea pigs in each group:group 1(experimental control group),treated with placebo pill(starch slices)for 3 days before noise exposure,group 2(experimental group),treated with Nuodikang Capsule for 3 days before noise exposure,guinea pigs in group 1 and group 2 was exposed to impulse noise with the same condition simultaneously,group 3(rhodiola group),only pretreated with Nuodikang Capsule for 3 days,without any other treatment and group 4(saline group),only pretreated with normal saline for 3 days,without any other treatment.Auditory brainstem response(ABR,auditory brainstem response)threshold was measured in all the guinea pigs before and after the experiment respectively.The cilium of hair cells were observed by scanning electron microscopy in the left cochlea.The expression of hypoxia-inducible factor-1 a(HIF-1 a,hypoxia-inducible factor-1 a),caspase-3 and 4-hydroxynonenal(4-hydroxynonenal,4-HNE)were detected by enzyme-linked immunosorbent assay(enzyme-linked immunosorbent assay,ELISA)in the right cochlea.changes of hearing threshold and the cilium of hair cells before and after the experiment and the expression of caspase-3,HIF-l?,4-HNE in different groups were compared among groups.Statistical analysisThe data were analyzed by SPSS version 20.0 software,the measurement data was expressed with the means ± standard deviation for each group.ABR thresholds were analyzed by paired sample t test and one-way ANOVA.The levels of caspase-3,HIF-1 ? and 4-HNE in cochlea were analyzed by one-way ANOVA.The correlation among caspase-3,HIF-1 alpha and 4-HNE in the cochlea was analyzed by Pearson analysis.LSD test was used to compare inter-group variables.The difference was significant(P<0.05).Results1.Hearing threshold:before the experiment,hearing threshold in group 1 was 10.50 ± 1.58dB,hearing threshold in group 2 was 11.50 ± 2.1 1dB,hearing threshold in group 3 was 10.25 ± 1.42dB,hearing threshold in group 4 was 11.00 ± 1.29dB.24 hours after the experiment,hearing threshold in group 1 was 49.50 ± 2.84dB,hearing threshold in group 2 was 27.75 ± 1.42dB,hearing threshold in group 3 was 10.75 ±1.67dB,hearing threshold in group 4 was 10.75 ± 1.21dB.There was no significant difference in ABR threshold among group 1,group 2,group 3 and group 4(P>0.05)before the experiment.24 hours after the experiment,there was significant difference in ABR threshold between group 1 and group 2(P<0.05),20dB of ABR threshold shift between group 1 and group 2 after the experiment,and there was significant difference(P<0.05).2.Morphological changes of cochlea:in group 1,there were large area deletions in cilium of outer hair cells in the cochlea observed by high power microscope.In group 2,the cilium of outer hair cells were damaged individually and scattered,there was no obvious damage in group 3 and group 4,and no cilium of inner hair cells were observed in four groups.3.The expression of caspase-3,HIF-1 alpha and 4-HNE in the cochlea:Content of caspase-3:content of caspase-3 in group 1 was 6.64 ± 0.54ng/g,content of caspase-3 in group 2 was 5.62 ± 0.41ng/g,content of caspase-3 in group 3 was 4.10 ± 0.40ng/g,content of caspase-3 in group 4 was 3.85 ± 0.48ng/g,the expression of caspase-3 in group 1 was significantly higher than that of group 2(P<0.05),group 3(P<0.05)and group 4(P<0.05),the expression of caspase-3 in group 2 was significantly higher than that of group 3(P<0.05),group 4(P<0.05),there was no significant difference between group 3 and group 4(P>0.05).Content of HIF-1 a:content of HIF-1 a in group 1 was 8.40 ± 0.56ug/g,content of HIF-1 a in group 2 was 5.29 ± 0.43ug/g,content of HIF-1 a in group 3 was 3.33 ± 0.20ug/g,content of HIF-1 a in group 4 was 3.55 ± 0.43ug/g,the expression of HIF-1 a in group 1 was significantly higher than that of group 2(P<0.05),group3(P<0.05)and group 4(P<0.05),the expression of HIF-1 a in group 2 was significantly higher than that of group 3(P<0.05),group 4(P<0.05),there was no significant difference between group 3 and group 4(P>0.05).Content of 4-HNE:content of 4-HNE in group 1 was 760.35 ± 51.30ug/g,content of 4-HNE in group 2 was 587.45 ± 44.00ug/g,content of 4-HNE in group 3 was 418.65 ± 39.00ug/g,content of 4-HNE in group 4 was 414.31 ± 14.30ug/g,the expression of 4-HNE in group 1 was significantly higher than that of group 2(P<0.05),group3(P<0.05)and group 4(P<0.05),the expression of 4-HNE in group 2 was significantly higher than that of group 3(P<0.05),group 4(P<0.05)4,there was no significant difference between group 3 and group 4(P>0.05).There were significantly different in the expression of caspase-3,HIF-1 alpha and 4-HNE respectively(F=24.674,P<0.05;F=90.258,P<0.05;F=51.663,P<0.05)among four groups,and the expression of caspase-3,HIF-1 alpha and 4-HNE in group 1 and group 2 were significantly higher than group 3 and group 4(P<0.05),and the expression of caspase-3,HIF-1 alpha and 4-HNE in group 1 was higher than group 2(P<0.05).The correlation analysis of caspase-3,HIF-1 alpha and 4-HNE among the four groups was no significantly correlated(P>0.05).ConclusionRhodiola can significantly reduce the ABR threshold after exposure to impulse noise,reduce the expression of caspase-3,HIF-1 alpha and 4-HNE in the cochlea,decrease the loss of cochlear outer hair cell cilium,it is conclude that rhodiola reduce NIHL through anti hypoxia and anti-oxidation. |
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