动物造模 z-bio 2022-03-01 258

　　Objective: To observe the relationship between guinea pig cochlear autophagy-related proteins beclin1 and LC3, Na+-K+-2Cl- co-transporter (NKCC1) mRNA, endothelin (ET) expression and cochlear gentamicin (GM) injury and piperphentonamine hydrochloride (PPTA) protection against injury and its mechanism.

　　METHODS: Sixty guinea pigs were randomly divided into control group, model group, concurrent treatment group, post-modeling control group, and post-treatment group. The control group was given NS+artificial perilymph, the model group was given GM+artificial perilymph, and the treatment group was given GM+PPTA (all were administered continuously for 7 d). Then artificial perilymph and PPTA were continuously injected for 7 days. All guinea pigs underwent surgical intubation of auditory bubbles before administration, NS and GM (160 mg·kg-1·d-1) were injected intraperitoneally, and artificial perilymph and PPTA were injected into auditory bubbles. After administration of guinea pigs in each group, the ABR test was used to analyze the hearing, and the expressions of beclin1 and LC3, NKCC1 mRNA and ET-1 were detected.

　　Results: There was no significant difference in the ABR results between the model group and the control group after modeling (P>0.05), but both were significantly higher than the other three groups (P<0.05). The ABR threshold of the guinea pigs in the treatment group at the same period was significantly lower than that in the later period. Treatment group (P<0.05); the expression levels of LC3Ⅱ and Beclin1 in the model group were significantly higher than those in the other 4 groups, and the expressions of LC3Ⅱ and Beclin1 in the later treatment group were lower than those in the control group after modeling; the expression of NKCC1 mRNA in the model group was higher than that in the other 4 groups significantly increased (P<0.05), and the expression of NKCC1 mRNA in the late treatment group was significantly lower than that in the control group after modeling (P<0.05). The expression of ET-1 in each part of the model group was significantly higher than that of the other 4 groups, the expression of ET-1 in each part of the control group was lower than that of the other 4 groups, and the expression of ET-1 in each part of the later treatment group was lower than that of the control group after modeling.

　　Conclusion: PPTA can inhibit the expression of autophagy, NKCC1 and ET-1 in cochlear cells, thus playing a protective effect on cochlear gentamicin damage; PPTA has a better effect against gentamicin cochlear damage in the early stage, suggesting that GM may have a protective effect on auditory cells. produce irreversible damage.