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目的观察一氧化氮合酶抑制剂——N-硝基左旋精氨酸甲酯(N~G-nitro-L-argininemethyl ester,L-NAME)和神经营养因子3(neurotrophin 3,NT3)对噪声性听力损失的保护作用。方法80只雄性杂色豚鼠按区组随机分为非噪声组(n=20)和噪声暴露组(n=60),噪声暴露组又分为生理盐水组(n=20)、L-NAME 组(n=20)、L-NAME+NT3组(n=20)。L-NAME 组和 L-NAME+NT3组动物在噪声暴露(4 kHz 倍频程、声压级115 dB,5 h)之前2 d 和噪声暴露前30 min 给予 L-NAME10 mg/kg(腹腔注射),生理盐水组动物给予等体积的生理盐水。NT3(10μ/ml)在噪声暴露前4 d 经微量渗透泵(200μl,0.5 μl/h)输入到 L-NAME+NT3组动物的右侧耳蜗鼓阶,持续到噪声暴露后10 d。噪声暴露前和暴露后10 d 测试听性脑干反应(auditory brainstem response,ABR),暴露后3 d 测试耳蜗组织一氧化氮(nitric oxide,NO)水平,最后一次 ABR 测试后计数耳蜗毛细胞的存活率。结果无噪声暴露组动物无明显的听力改变和毛细胞缺失;生理盐水组动物的 ABR 阈移、毛细胞缺失率及耳蜗组织 NO 水平均高于 L-NAME 组和 L-NAME+NT3组,差异有统计学意义(P 值均<0.01);与 L-NAME 组相比,L-NAME+NT3组豚鼠的 ABR 阈移减小,差异有统计学意义(P<0.01),而耳蜗组织NO 水平和毛细胞缺失率差异则没有统计学意义(P=0.197及 P=0.095)。结论与单独给予 L-NAME 相比,联合使用 NT3可以更大程度减轻噪声对豚鼠耳蜗的损伤。
Objective To observe the effects of nitric oxide synthase inhibitor N-G-nitro-L-arginine methyl ester (L-NAME) and neurotrophin 3 (NT3) Sexual hearing loss protection. Methods Eighty male pigmented guinea pigs were randomly divided into non-noise group (n = 20) and noise exposure group (n = 60). The noise exposure group was further divided into normal saline group (n = 20), L-NAME group (n = 20), L-NAME + NT3 group (n = 20). L-NAME group and L-NAME + NT3 group were given L-NAME 10 mg / kg (ip) intraperitoneally before noise exposure (4 kHz octave, sound pressure level 115 dB, 5 h) and 30 min before noise exposure ), Saline group animals were given equal volume of saline. NT3 (10μ / ml) was infiltrated into the right cochlea of L-NAME + NT3 animals through micro osmotic pump (200μl, 0.5μl / h) 4 days before noise exposure for 10 days. The auditory brainstem response (ABR) was measured before noise exposure and at 10 days after exposure. The levels of nitric oxide (NO) in the cochlea were measured 3 days after exposure. The cochlear hair cells were counted after the last ABR test Survival rate. Results There was no significant change in hearing and hair loss in the animals without noise exposure. ABR threshold shift, loss of hair cells and NO level in cochlear of saline group were higher than those in L-NAME group and L-NAME + NT3 group (P <0.01). Compared with L-NAME group, the ABR threshold of guinea pigs in L-NAME + NT3 group was significantly lower than that in L-NAME group (P <0.01) And hair loss rate difference was not statistically significant (P = 0.197 and P = 0.095). Conclusions Compared with L-NAME alone, the combined use of NT3 can reduce the damage of guinea pig cochlea to a greater extent.