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硫酸卡那霉素聯(lián)合呋塞米快速致聾大鼠模型的研究

發(fā)布時(shí)間:2019-04-02 20:20
【摘要】:目的觀察硫酸卡那霉素(kanamycin sulfate,KM)與呋塞米(furosemide,Fur)聯(lián)合用藥建立藥物性快速致聾大鼠動(dòng)物模型的效果。方法 32只SD大鼠隨機(jī)分為A組(KM+Fur后1天組)、B組(KM+Fur后7天組)、C組(KM+Fur后14天組)、D組(對照組),每組8只動(dòng)物。A、B、C三組分別經(jīng)一次性腹腔注射KM 500mg/kg,30分鐘后再經(jīng)腹腔注射Fur 0.2ml/kg,空白對照組按體重給予相同劑量生理鹽水。各組在相應(yīng)的時(shí)間點(diǎn)完成聽性腦干反應(yīng)(auditory brainstem response,ABR)檢測當(dāng)天,分別行耳蝸基底膜鋪片及掃描電鏡觀察耳蝸毛細(xì)胞損傷情況,免疫熒光染色觀察螺旋神經(jīng)節(jié)細(xì)胞亡情況。結(jié)果 A、B、C組各頻率ABR閾值較正常對照組明顯升高(P0.05);而A、B、C組各頻率ABR反應(yīng)閾差異無統(tǒng)計(jì)學(xué)意義(P0.05)。A、B、C組耳蝸底回外毛細(xì)胞明顯缺失,纖毛排列紊亂,螺旋神經(jīng)節(jié)細(xì)胞的半胱氨酸天冬氨酸蛋白酶-3(cleaved caspase-3)的表達(dá)量較正常對照組均明顯增加(P0.05)。結(jié)論硫酸卡那霉素和呋塞米聯(lián)合單次腹腔用藥24小時(shí)后大鼠ABR反應(yīng)閾明顯增高,并可見耳蝸底回毛細(xì)胞的明顯缺失,KM+Fur聯(lián)合應(yīng)用是簡單、快速而有效的大鼠耳聾動(dòng)物模型建模方法。
[Abstract]:Objective To observe the effect of Kanamycin sulfinate (KM) and furosemide (Fur) on the establishment of an animal model of drug-induced rapid deafness. Methods 32 SD rats were randomly divided into group A (1 day after KM + Fur), group B (7 days after KM + Fur), group C (14 days after KM + Fur), group D (control group), and 8 animals in each group. The three groups of A, B and C were intraperitoneally injected with KM 500 mg/ kg and then injected into the abdominal cavity for 0.2 ml/ kg for 30 minutes, and the blank control group was given the same dose of physiological saline according to the weight. The results of auditory brainstem response (ABR) were performed at the corresponding time points, and the damage of the hair cells of the cochlea was observed by scanning the basal membrane of the cochlea and the scanning electron microscope, respectively, and the apoptosis of the spiral ganglion cells was observed by immunofluorescence staining. Results The ABR threshold in group A, B and C was significantly higher than that in the normal control group (P0.05). The difference of ABR threshold in group A, B and C was not significant (P0.05). The expression of caspase-3 in the spiral ganglion cells increased significantly in the control group (P0.05). Conclusion The response threshold of the ABR in the rat is obviously increased after 24 hours of single intraperitoneal administration of kanamycin and pemide, and the obvious deletion of the back hair cells in the cochlea is found. The combined application of KM + Fur is a simple, rapid and effective model for modeling the rat's deafness.
【作者單位】: 第四軍醫(yī)大學(xué)西京醫(yī)院耳鼻咽喉頭頸外科;新疆生產(chǎn)建設(shè)兵團(tuán)醫(yī)院(石河子大學(xué)醫(yī)學(xué)院第二附屬醫(yī)院)耳鼻咽喉科;蘭州軍區(qū)臨潼療養(yǎng)院第二療養(yǎng)區(qū)耳鼻咽喉科;
【基金】:國家自然科學(xué)基金青年項(xiàng)目(81100713);國家自然科學(xué)基金海外重大合作項(xiàng)目(81120108008) 國家“973”項(xiàng)目課題(2011CB504505)資助
【分類號】:R764.43

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