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Objective: To study the protective effects of metformin on noise-induced hearing loss (NIHL) and its differential protein omics expression profile. Methods: In January 2021, 39 male Wistar rats were randomly divided into control group, noise exposure group and metformin+noise exposure group, with 13 rats in each group. Rats in the noise exposure group and metformin+noise exposure group were continuously exposed to octave noise with sound pressure level of 120 dB (A) and center frequency of 8 kHz for 4 h. Rats in the metformin+noise exposure group were treated with 200 mg/kg/d metformin 3 d before noise exposure for a total of 7 d. Auditory brainstem response (ABR) was used to test the changes of hearing thresholds before noise exposure and 1, 4, 7 d after noise exposure in the right ear of rats in each group. Tandem mass tag (TMT) quantitative proteomics was used to identify and analyze the differentially expressed protein in the inner ear of rats in each group, and it was verified by immunofluorescence staining with frozen sections. Results: The click-ABR thresholds of right ear in the noise exposure group and metformin+noise exposure group were significantly higher than those in the control group 1, 4, 7 d after noise exposure (P<0.05) . The click-ABR threshold of right ear in the metformin+noise exposure group were significantly lower than that in the noise exposure group (P<0.05) . Compared with the noise exposure group, 1035 up-regulated proteins and 1145 down-regulated proteins were differentially expressed in the metformin+noise exposure group. GO enrichment analysis showed that the significantly differentially expressed proteins were mainly involved in binding, molecular function regulation, signal transduction, and other functions. Enrichment analysis of KEGG pathway revealed that the pathways for significant enrichment of differentially expressed proteins included phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) signaling pathway, focal adhesion, diabetic cardiomyopathy, mitogen, and mitogen-activated protein kinase (MAPK) signaling pathway. Immunofluorescence experiments showed that compared with the noise exposure group, the fluorescence intensity of insulin-like growth factor 1 receptor (IGF1R) in the metformin+noise exposure group was increased, and the fluorescence intensity of eukaryotic translation initiation factor 4E binding protein 1 (eIF4EBP1) was decreased. Conclusion: Noise exposure can lead to an increase in rat hearing threshold, and metformin can improve noise-induced hearing threshold abnormalities through multiple pathways and biological processes.
Assuntos
Animais , Masculino , Ratos , Limiar Auditivo/fisiologia , Cóclea , Orelha Interna , Potenciais Evocados Auditivos do Tronco Encefálico/fisiologia , Perda Auditiva Provocada por Ruído/prevenção & controle , Metformina/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Ratos WistarRESUMO
<p><b>OBJECTIVE</b>To study the effect of chronic noise exposure on expression of N-methyl-D-aspartic acid receptor 2B (NR2B) and tau phosphorylation in hippocampus of rats.</p><p><b>METHODS</b>Twenty-four male SD rats were divided in control group and chronic noise exposure group. NR2B expression and tau phosphorylation in hippocampus of rats were detected after chronic noise exposure (100 dB SPL white noise, 4 h/d×30d) and their mechanisms underlying neuronal apoptosis in hippocampus of rats with TUNEL staining.</p><p><b>RESULTS</b>The NR2B expression decreased significantly after chronic noise exposure which resulted in tau hyperphosphorylation and neural apoptosis in hippocampus of rats. Immunohistochemistry showed that the tau hyperphosphorylation was most prominent in dentate gyrus (DG) and CA1 region of rat hippocampus.</p><p><b>CONCLUSION</b>The abnormality of neurotransmitter system, especially Glu and NR2B containing NMDA receptor, and tau hyperphosphorylation in hippocampus of rats, may play a role in chronic noise-induced neural apoptosis and cognition impairment.</p>
Assuntos
Animais , Masculino , Ratos , Apoptose , Hipocampo , Biologia Celular , Metabolismo , Neurônios , Biologia Celular , Metabolismo , Ruído , Fosforilação , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , Metabolismo , Proteínas tau , MetabolismoRESUMO
<p><b>OBJECTIVE</b>To explore the effects of retinol acid (RA) and triiodothyronine (T3) on alleviating the impairment of cognitive function by sleep deprivation (SD).</p><p><b>METHODS</b>Male Wistar rats were divided into 4 groups: control group (C group), sleep deprivation group (SD group), sleep deprivation + RA group (SD + RA group) and sleep deprivation + T3 group (SD + T3 group). Open field test (OFT) was used to observe the nervous behavior of the rats after SD and electrophysiological brain stereotactic method was used to test long-term potentiation (LTP) in dentate gyrus (DG) of the rats. Ng protein expression was determined by Western blot.</p><p><b>RESULTS</b>Compared with the SD group, the number of crossing in OFT, the changes of amplitude of population spike (PS) and the expression of Ng protein in hippocampus were higher significantly in the SD + RA and SD + T3 groups. All of these had not significant difference comparing with the C group.</p><p><b>CONCLUSION</b>RA and T3 may alleviate the restrain state of neural system after SD by augmenting the expression of Ng protein in hippocampus.</p>
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Animais , Masculino , Ratos , Cognição , Giro Denteado , Metabolismo , Potenciação de Longa Duração , Neurogranina , Metabolismo , Ratos Wistar , Privação do Sono , Metabolismo , Psicologia , Tri-Iodotironina , Farmacologia , Vitamina A , FarmacologiaRESUMO
<p><b>AIM</b>To study the effects of noise on event-related potential(ERP) and its mechanism in hippocampus in rats.</p><p><b>METHODS</b>Male SD rats were divided into 2 groups: control group (CG) and noise exposure group(NG). The rats in NG were exposed to white noise 105 dB SPL for 2.5 h/d x 20 d. P300 were recorded at parietal bone in rats. The Nissl body, NMDAR2B and [Ca2+]i of neurons in hippocampus were analyzed.</p><p><b>RESULTS</b>The peak latency (PL) of ERP P3a, P3 and P3b in NG were significantly longer than that in CG in the 14th and 20th exposure day. The amount of Nissl body in dentate gyrus (DG) and CA1 region and NMDAR2B in DG, CA1 and CA3 region of hippocampus of NG were significantly decreased than those of CG as well, while the concentration of Ca2+ in neurons increased markedly in NG.</p><p><b>CONCLUSION</b>Decreased Nissl body and NMDAR2B and increased [Ca2+]i in hippocampus in long-term noise exposed rats might cause the change of ERP P300.</p>
Assuntos
Animais , Masculino , Ratos , Cálcio , Metabolismo , Exposição Ambiental , Potenciais Evocados P300 , Fisiologia , Hipocampo , Metabolismo , Fisiologia , Neurônios , Metabolismo , Fisiologia , Corpos de Nissl , Metabolismo , Ruído , Distribuição Aleatória , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato , MetabolismoRESUMO
<p><b>AIM</b>To explore the protective effect of L-arginine on isolated rat heart with ischemia/reperfusion injury.</p><p><b>METHODS</b>24 wistar rats were randomly divided into 3 groups (each 8): control group, ischemia group, L-arginine group. The myocardiac relatively ischemia/reperfusion models in vitro were set up by using weak current stimulating isolated rat hearts. During the pre-ischemia, post-ischemia 15 min and post-ischemia 30 min, the coronary fluid was collected for testing contents of MDA and activities of both CK and LDH. Cardiac functional indexes were recorded through Pclab. At the time of 5 min, 10 min, 20 min, 30 min after ischemia, the recovery of PRP, + DP/dt(max) and - DP/dt(max) were calculated.</p><p><b>RESULTS</b>(1) During the reperfusion, L-arginine group achieved better recovery of cardiac function than that of the ischemia group. (2) MDA content, CK and LDH activities both in the coronary fluid and in the myocardium of L-arginine group were lower than those of the ischemia group, while SOD activities in the myocardium of L-arginine group were higher than that of the ischemia group.</p><p><b>CONCLUSION</b>To some extent, L-arginine could protect the myocardium from ischemia/reperfusion injury.</p>
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Animais , Masculino , Ratos , Arginina , Farmacologia , Coração , Traumatismo por Reperfusão Miocárdica , Miocárdio , Metabolismo , Ratos WistarRESUMO
<p><b>AIM</b>To investigate the mechanism of protection by sound conditioning from acoustic trauma.</p><p><b>METHODS</b>Sound conditioning experimental model of animals was established. The expression of CaM, HSP70 and F-actin in hair cells were examined with the method of immunohistochemistry. Free calcium concentration in hair cells was observed by LSCM at the same time. Quantitative investigation was devised to assess the changes of F-actin, CaM, HSP70 and intracellular calcium concentration in hair cells.</p><p><b>RESULTS</b>The expression of CaM, HSP70 and F-actin all showed an increased trend after noise exposure. HSP70 and F-actin expressed significantly more in group CH than that expressed in group H. Compared with group H, the expression of CaM showed an increased trend in group CH. Elevation of intracellular calcium concentration could be resulted from noise exposure. The calcium concentration in group H was significantly higher than that in group C and group CH.</p><p><b>CONCLUSION</b>A suitable sound conditioning can make the auditory system of guinea pig more resistant to noise trauma. The strengthened cytoskeleton system and the intracellular calcium homeostasis play a critical role in the protective mechanism of sound conditioning.</p>