庆大霉素对耳蜗血管纹细胞ET-A表达的影响及阿魏酸钠的保护作用
发布时间：2019-07-02 15:20
【摘要】： 研究背景和目的：庆大霉素是一种临床应用较为普遍的氨基糖甙类抗生素,其耳毒性所致的感音神经性聋较为常见,但其耳毒性机理尚不清楚,目前尚无理想的方法进行预防。本课题通过构建庆大霉素致聋大鼠模型,观察庆大霉素致耳毒性过程中耳蜗基底膜毛细胞的形态变化情况,耳蜗外侧壁血管纹毛细血管网的病理改变及ET-A的表达变化情况,以研究庆大霉素耳毒性的可能机制,并进一步探讨阿魏酸钠对庆大霉素耳毒性的保护作用,从而寻求降低庆大霉素耳毒性的方法。 研究方法：将32只Wistar大鼠随机分成三组：对照组(n=8只)、庆大霉素组(n=13只,150 mg／kg肌注7天)、庆大霉素(150 mg／kg肌注7天)和阿魏酸钠(50 mg／kg肌注7天)联合用药组(n=11只),分别建立动物模型。应用脑干诱发电位仪检测各组大鼠用药前后的脑干诱发电位听阈(auditory brainstem response, ABR)变化；分别采用基底膜铺片和血管纹铺片观察各组大鼠耳蜗毛细胞及微循环的形态变化情况；应用免疫组化SP法观察各组药物对耳蜗外侧壁内皮素A(ET-A)受体的表达情况的影响。采用SPSS13.0统计软件对ABR变化情况的组间比较和各组ET-A的表达变化比较均采用校正t检验进行统计分析。 研究结果：肌注庆大霉素组大鼠ABR听阈较对照组显著提高(P0.05)且庆大霉素组的ABR变化显著高于联合用药组ABR的听阈变化,差异具有统计学意义(P＜0.05)；联合用药组ABR变化略高于对照组ABR变化,P0.05,差异无统计学意义(P＞0.05)。庆大霉素组毛细胞排列杂乱、出现明显缺失,血管纹毛细血管网呈明显收缩缺血状态；联合用药组毛细胞排列紊乱、散在缺失,血管纹毛细血管网无明显收缩缺血改变。ET-A主要分布于血管纹中间细胞和微血管壁周围细胞,对照组与联合用药组呈弱阳性(+),庆大霉素组呈强阳性(+++)。 研究结论： 1.庆大霉素肌肉注射可显著提高大鼠的听阈,引起明显的听力下降,阿魏酸钠可有效拮抗庆大霉素对大鼠的耳毒性作用,保护大鼠听力。 2.庆大霉素可引起耳蜗毛细胞的坏死凋亡及耳蜗外侧壁血管纹毛细血管网强烈收缩,提示庆大霉素可引起耳蜗外侧壁微循环障碍,推测耳蜗外侧壁微循环障碍参与庆大霉素耳毒性作用；阿魏酸钠与庆大霉素联合用药可有效保护毛细胞减轻损伤,改善耳蜗外侧壁微循环。 3.耳蜗外侧壁ET-A可能参与庆大霉素致耳毒性的过程,阿魏酸钠可能通过抑制ET-A作用来拮抗庆大霉素的毒副作用。 4.庆大霉素耳毒性引起的耳蜗外侧壁微循环障碍和ET-A表达的增加可能为明确氨基糖甙类药物致耳毒性的机制提供理论依据,阿魏酸钠的有效保护作用可能为临床氨基糖甙类药物致耳毒性的预防治疗提供新的治疗策略。
[Abstract]:The background and purpose of the study: Gentamicin is a common amino-sugar-type antibiotic in clinical application. The sensorineural hearing loss caused by ototoxicity is more common, but the mechanism of ototoxicity is not clear, and there is no ideal method for prevention at present. In this study, a model of gentamicin-induced deafness was constructed to observe the morphological changes of the hair cells in the basilar membrane of the cochlea during the ototoxicity of the gentamicin, the pathological changes of the capillary network of the external wall of the cochlea and the change of the expression of ET-A. To study the possible mechanism of gentamicin ototoxicity, and to further study the protective effect of sodium ferulate on the ototoxicity of gentamicin, the method of reducing the ototoxicity of gentamicin was sought. Methods:32 Wistar rats were randomly divided into three groups: control group (n = 8), gentamicin group (n = 13,150 mg/ kg muscle injection for 7 days), gentamicin (150 mg/ kg intramuscular injection for 7 days) and sodium ferulate (50 mg/ kg intramuscular injection for 7 days). 1), respectively set up A brain-stem evoked potential (BAEP) was used to detect the changes of the auditory brainstem response (ABR) in the rat's cochlea before and after the treatment. The expression of endothelin A (ET-A) receptor in the outer wall of the cochlea was observed by immunohistochemical SP method. The effect of the statistical software of SPSS13.0 on the change of the ABR and the change of the expression of ET-A in each group were compared with the corrected t-test. The results of the study showed that the ABR threshold in the gentamycin group was significantly higher than that in the control group (P0.05), and the ABR change of the gentamycin group was significantly higher than that of the ABR in the combination group (P <0.05). The ABR of the combined group was slightly higher than that of the control group. The difference was not significant (P <0.05) (P <0.05). P> 0.05). The hair cells of the gentamycin group were arranged in a disorder, the appearance of the hair cells in the vein was obviously absent, and the capillary network of the blood vessel was in the state of ischemia. The arrangement of hair cells in the combination group was disordered, and the capillary network of the vein pattern was not clear. ET-A was mainly distributed in the peripheral cells of the vessel and the peripheral cells of the microvessel wall. The control group and the combination group showed a weak positive (+) and the gentamycin group was strong. Positive (+ + Conclusion:1. The results of the study:1. The intramuscular injection of gentamicin can significantly improve the hearing threshold of the rat, cause a significant decrease in the hearing, and the sodium ferulate can effectively antagonize the gentamicin. 2. Gentamicin can cause the necrosis of the hair cells of the cochlea and the strong contraction of the capillary network of the external wall of the cochlea, suggesting that the gentamicin can cause the microcirculation disturbance of the outside wall of the cochlea, and the cochlea can be presumed. The microcirculatory disturbance of the lateral wall is involved in the ototoxicity of gentamicin; the combination of sodium ferulate and gentamicin can be effectively preserved. 3. The lateral wall ET-A of the cochlea may be involved in the ototoxicity of the gentamicin, and the sodium ferulate may Can antagonize the toxic and side effects of gentamicin by inhibiting the effect of ET-A. It is possible to provide a theoretical basis for the mechanism of the ototoxicity of a clear amino sugar drug, and the effective protection of sodium ferulate may
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764.35
[Abstract]:The background and purpose of the study: Gentamicin is a common amino-sugar-type antibiotic in clinical application. The sensorineural hearing loss caused by ototoxicity is more common, but the mechanism of ototoxicity is not clear, and there is no ideal method for prevention at present. In this study, a model of gentamicin-induced deafness was constructed to observe the morphological changes of the hair cells in the basilar membrane of the cochlea during the ototoxicity of the gentamicin, the pathological changes of the capillary network of the external wall of the cochlea and the change of the expression of ET-A. To study the possible mechanism of gentamicin ototoxicity, and to further study the protective effect of sodium ferulate on the ototoxicity of gentamicin, the method of reducing the ototoxicity of gentamicin was sought. Methods:32 Wistar rats were randomly divided into three groups: control group (n = 8), gentamicin group (n = 13,150 mg/ kg muscle injection for 7 days), gentamicin (150 mg/ kg intramuscular injection for 7 days) and sodium ferulate (50 mg/ kg intramuscular injection for 7 days). 1), respectively set up A brain-stem evoked potential (BAEP) was used to detect the changes of the auditory brainstem response (ABR) in the rat's cochlea before and after the treatment. The expression of endothelin A (ET-A) receptor in the outer wall of the cochlea was observed by immunohistochemical SP method. The effect of the statistical software of SPSS13.0 on the change of the ABR and the change of the expression of ET-A in each group were compared with the corrected t-test. The results of the study showed that the ABR threshold in the gentamycin group was significantly higher than that in the control group (P0.05), and the ABR change of the gentamycin group was significantly higher than that of the ABR in the combination group (P <0.05). The ABR of the combined group was slightly higher than that of the control group. The difference was not significant (P <0.05) (P <0.05). P> 0.05). The hair cells of the gentamycin group were arranged in a disorder, the appearance of the hair cells in the vein was obviously absent, and the capillary network of the blood vessel was in the state of ischemia. The arrangement of hair cells in the combination group was disordered, and the capillary network of the vein pattern was not clear. ET-A was mainly distributed in the peripheral cells of the vessel and the peripheral cells of the microvessel wall. The control group and the combination group showed a weak positive (+) and the gentamycin group was strong. Positive (+ + Conclusion:1. The results of the study:1. The intramuscular injection of gentamicin can significantly improve the hearing threshold of the rat, cause a significant decrease in the hearing, and the sodium ferulate can effectively antagonize the gentamicin. 2. Gentamicin can cause the necrosis of the hair cells of the cochlea and the strong contraction of the capillary network of the external wall of the cochlea, suggesting that the gentamicin can cause the microcirculation disturbance of the outside wall of the cochlea, and the cochlea can be presumed. The microcirculatory disturbance of the lateral wall is involved in the ototoxicity of gentamicin; the combination of sodium ferulate and gentamicin can be effectively preserved. 3. The lateral wall ET-A of the cochlea may be involved in the ototoxicity of the gentamicin, and the sodium ferulate may Can antagonize the toxic and side effects of gentamicin by inhibiting the effect of ET-A. It is possible to provide a theoretical basis for the mechanism of the ototoxicity of a clear amino sugar drug, and the effective protection of sodium ferulate may
【学位授予单位】：山东大学
【学位级别】：硕士
【学位授予年份】：2010
【分类号】：R764.35
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相关期刊论文 前10条
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