Experimental Study On The Regulation Of Autophagy-related Protein Expression In The Cochlea Of Rats With Cisplatin-induced Deafness By Ligustrazin

Objective In this study,cisplatin(Carboplatin,DDP)induced deafness rats were used as models,and(Tetramethylpyrazine,TMP)was injected to interfere with the model.To observe the effects of TMP on the expression of autophagy related proteins LC3-Ⅰ,LC3-Ⅱ and P62 in cochlea of DDP-induced hearing loss rats,and further discuss the intervention effect and mechanism of TMP on DDP-induced hearing loss rats.This test can reveal the possible mechanism that TMP can inhibit DDP induced deafness in rats,so as to prevent both disease and disease in the future clinical application of DDP.Material and method A total of 110 healthy SD rats with normal hearing were randomly divided into two groups after 7 days of routine adaptive breeding.The model group(n=65)was injected with cisplatin.The control group(n=45)was intraperitoneally injected with the same amount of normal saline.After 5 days of continuous infusion,5 rats in each group were injected into the abdominal cavity with 10% chloral hydrate(3ml/kg)for anesthesia,and the Dantec-REVOL brain stem induced potentiometer was operated in the sound insulation room for model evaluation.The control group was randomly assigned to the normal control group and the ligustrazine control group.Model group was randomly assigned to model control group(n=20),tetramethylpyrazine treatment group(n=20)and 3-MA group(n=20)for 7 consecutive days.On the next day of the last administration,the rats were killed by excessive anesthesia,and their heads were severed immediately,and the remaining structures and tissues were stripped away,leaving only the intact cochlea.In this study,the expression levels of autophagy proteins LC3-Ⅰ,LC3-Ⅱ and P62 in cochlear tissues of rats in each experimental group were detected by immunohistochemical and Western-blot methods.spss23.0 software was used for statistical analysis."±s" was used for measurement data in the results.One-way analysis of variance was used for data comparison among multiple groups,and "P<0.05" was used for statistical difference.Results Compared with 3-MA group,the ratio of LC3-Ⅱ/LC3-Ⅰ in blank control group and Ligustrazine control group was slightly increased(P<0.05).Compared with blank control group,the expression level of P62 protein in cochlea tissue decreased in model control group and ligustrazine treatment(P<0.01).Compared with model control group,the expression level of P62 protein in cochlea decreased after ligustrazine treatment,while the protein expression level in 3-MA group increased,with statistically significant differences(P<0.01).Compared with blank control group,the protein expression levels of LC3-Ⅰ and LC3-Ⅱ in cochlea tissue increased in model control group and ligustrazine treatment,with statistically significant difference(P<0.01).Compared with the protein expression levels of LC3-Ⅰ and LC3-Ⅱ in cochlear tissues of model control group,the histone expression level of ligustrazine treatment increased,while the histone expression level of 3-MA decreased,with statistically significant difference(P<0.01).Conclusion The up-regulated expression levels of autophagy related proteins LC3-Ⅰand LC3-Ⅱ and down-regulated expression levels of P62 in rat cochlea may be relate d to the important mechanism that TMP can regulate DDP induced deafness in rats.T MP can promote the occurrence of protective autophagy in cochlea,thereby inhibiting cisplatin-induced hearing damage.