葛根素对庆大霉素毒性小鼠p53-ROS通路和螺旋神经元的细胞学的影响机制研究

A Study on the Mechanisms of Puerarin’s Effects on the p53-ROS Pathway and Spiral Neurons in Gentamicin Toxic Mice

摘要: 目的：探讨葛根素注射液在庆大霉素毒性小鼠中的作用效果及对p53-ROS通路和螺旋神经元细胞学的影响。方法：购置SPF级C57BL/6J小鼠30只，随机取10只为空白对照组；其余小鼠建立庆大霉素耳毒性模型，建模成功后随机分为模型对照组和葛根素组各10只。空白对照组和模型对照组不采取任何措施，葛根素组采用葛根素注射液腹腔注射，比较3组小鼠听力水平、耳蜗形态学变化及p53-ROS通路关键蛋白水平。结果：葛根素组ABR低于模型对照组(P < 0.05)；高于空白对照组(P < 0.05)；模型对照组ABR高于空白对照组(P < 0.05)；葛根素组干预14 d后听力水平0.75 kHz、1.0 kHz、2.0 kHz、4.0 kHz及8.0 kHz小鼠DPOAE水平高于模型对照组(P < 0.05)；HE染色结果表明，葛根素组经药物干预后耳蜗部位毛细胞数量减少，耳蜗底转血管纹细胞未见水肿，形态正常。葛根素组Bax、Bcl-2及Cytochrome C mRNA及相关蛋白水平低于模型对照组(P < 0.05)。结论：葛根素用于庆大霉素毒性小鼠动物模型中效果显著，能抑制p53-ROS通路，改善螺旋神经元的细胞学水平，有助于提升小鼠听力水平。

Abstract: Objective: To explore the effects of puerarin injection on gentamicin induced toxicity in mice and its effects on the p53-ROS pathway and spiral neuron cytology. Method: 30 SPF grade C57BL/6J mice were purchased, and 10 mice were randomly selected as the blank control group; The remaining mice were established with gentamicin ototoxicity models, and after successful modeling, they were randomly divided into a model control group and a puerarin group, with 10 mice in each group. No measures were taken in the blank control group and model control group, while the puerarin group was injected intraperitoneally with puerarin injection. The hearing levels, cochlear morphological changes, and key protein levels of the p53-ROS pathway were compared among the three groups of mice. Result: The ABR of the puerarin group was lower than that of the model control group (P < 0.05) and higher than the blank control group (P < 0.05); The ABR of the model control group was higher than that of the blank control group (P < 0.05); After 14 days of intervention with puerarin, the DPOAE levels in mice with hearing levels of 0.75 kHz, 1.0 kHz, 2.0 kHz, 4.0 kHz, and 8.0 kHz were higher than those in the model control group (P < 0.05); The HE staining results showed that after drug intervention, the number of hair cells in the cochlea of the puerarin group decreased, and there was no edema in the vascularized striated cells at the cochlea floor, with normal morphology. The levels of Bax, Bcl-2, Cytochrome C mRNA and related proteins in the puerarin group were lower than those in the model control group (P < 0.05). Conclusion: Puerarin has a significant effect in a mouse model of gentamicin toxicity, inhibiting the p53-ROS pathway, improving the cytological lev-el of spiral neurons, and helping to enhance the hearing level of mice.