本文關(guān)鍵詞： Ouabain 毛細(xì)胞 螺旋神經(jīng)節(jié) 聽力損失　出處：《南京醫(yī)科大學(xué)》2013年碩士論文　論文類型：學(xué)位論文

【摘要】：Ouabain是一種有效的Na+/K+-ATP酶抑制劑，曾作為臨床治療心衰的藥物使用，其地位現(xiàn)已經(jīng)被地高辛所取代。在內(nèi)耳中，同樣分布著大量的Na+/K+-ATP酶，其對維持內(nèi)、外淋巴鉀離子梯度及各細(xì)胞功能穩(wěn)定起著重要作用。研究顯示，將Ouabain應(yīng)用于動物內(nèi)耳，可造成不同程度的螺旋神經(jīng)節(jié)細(xì)胞和毛細(xì)胞損害。在沙鼠，Ouabain可特異性損傷螺旋神經(jīng)節(jié)I型神經(jīng)元，制造出聽神經(jīng)病動物模型，進(jìn)一步用于聽神經(jīng)病發(fā)病機(jī)制及治療方法的研究；而在豚鼠，ouabain主要損傷耳蝸毛細(xì)胞。貴州小型豬與人類的種屬差異性更小，在很多疾病與人類有共同的發(fā)病機(jī)制，，在內(nèi)耳疾病研究中，小型豬與嚙齒類動物相比也具有很多優(yōu)勢。本實(shí)驗(yàn)中選用在進(jìn)化上與人類更為接近的小型豬，進(jìn)一步研究ouabain對大體型動物內(nèi)耳的影響。 目的：探討短時間局部應(yīng)用不同濃度ouabain溶液對貴州小型豬內(nèi)耳的作用，分析內(nèi)耳形態(tài)及聽力改變與藥物濃度關(guān)系。 方法：于圓窗龕處局部應(yīng)用不同濃度ouabain或生理鹽水，實(shí)驗(yàn)動物分為1mMouabain組、0.1mMouabain組、生理鹽水對照組及空白對照組。采用聽性腦干反應(yīng)（auditorybrainstemresponse，ABR）測定、免疫組織化學(xué)染色等方法，觀察各組動物在應(yīng)用藥物后3天、一周及兩周時耳蝸內(nèi)螺旋神經(jīng)節(jié)和毛細(xì)胞的形態(tài)、數(shù)目及聽功能變化。 結(jié)果：生理鹽水對照組及空白對照組在術(shù)后內(nèi)耳形態(tài)及聽功能方面無明顯變化。與空白對照組相比，1mM組螺旋神經(jīng)節(jié)細(xì)胞明顯減少，0.1mM組損傷相對較輕；術(shù)后兩周時，1mM組毛細(xì)胞排列紊亂，數(shù)量無明顯減少，0.1mM組毛細(xì)胞基本無變化；1mM組及0.1mM組ABR閾值均較對照組顯著升高（P0.01），其中1mM組比0.1mM組升高更明顯（P0.05）。 結(jié)論：不同濃度ouabain溶液對貴州小型豬螺旋神經(jīng)節(jié)細(xì)胞均有損害作用，損傷程度與藥物濃度呈正相關(guān)，耳蝸毛細(xì)胞受損相對較輕，而對聽功能的影響較為明顯。
[Abstract]:Ouabain is an effective Na / K -ATPase inhibitor, which has been used as a clinical drug for the treatment of heart failure, and its status has been replaced by digoxin. There are also a large number of Na / K-ATPase, which plays an important role in maintaining the gradient of potassium ions in the endolymphatic and perilymphatic and the functional stability of the cells. It has been shown that Ouabain is used in the inner ear of animals. In the gerbils, the spiral ganglion type I neurons were specifically damaged, and the animal model of auditory neuropathy was made. To further study the pathogenesis and treatment of auditory neuropathy; However, in guinea pigs, the cochlear hair cells were mainly damaged. The difference between Guizhou miniature pigs and human species was even smaller, and there were common pathogenesis between many diseases and human beings, and in the study of inner ear diseases. Compared with rodents, miniature pigs have many advantages. In this study, the effects of ouabain on the inner ear of large animals were studied. Objective: to investigate the effects of local administration of different concentrations of ouabain solution on the inner ear of Guizhou miniature pig, and to analyze the relationship between the shape of the inner ear and the changes of hearing and drug concentration. Methods: the animals were divided into 1 m Mouabain group and 0.1 m Mouabain group with different concentrations of ouabain or normal saline. The auditory brainstem response (ABR) and immunohistochemical staining were used in normal saline control group and blank control group. The morphology, number and auditory function of spiral ganglion and hair cells in cochlea were observed 3 days, 1 week and 2 weeks after administration. Results: there were no significant changes in the shape and auditory function of the inner ear in the saline control group and the blank control group, but the number of spiral ganglion cells decreased significantly in the 1 mm group compared with the blank control group. The injury was relatively mild in 0.1 mm group. At two weeks after operation, the hair cells in the 1st mm group were disordered, and the number of hair cells in 0.1 mm group was not significantly decreased. The ABR threshold of 1mm group and 0.1 mm group were significantly higher than that of the control group, especially the 1mm group was significantly higher than the 0.1 mm group. Conclusion: different concentrations of ouabain solution can damage spiral ganglion cells of Guizhou miniature pigs. The degree of injury is positively correlated with the concentration of drug, and the damage of cochlear hair cells is relatively mild. But the effect on hearing function is obvious.
【學(xué)位授予單位】：南京醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2013
【分類號】：R764.4;R965

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