Objective Autoimmune inner ear disease is one of the inner ear diseases that can be effectively treated clinically, and researches on it have significant clinical and practical value.This study explored the immunoregulating and therapeutic effects of the mi-croRNA-146a recombinant lentiviral vector (RLV) on immune-medicated inner ear disease (IMIED) in guinea pigs so as to avoid the adverse reactions of the currently used immunodepressants. Methods IMIED models were established in 30 guinea pigs by immuni-zation with keyhole limpet hemocyanin and divided into three groups: microRNA-146a RLV, empty lentiviral vector ( ELV) control, and surgery simulation control, microinjected via the scala tympani with microRNA-146a RLV, ELV, and PBS, respectively.Before and after immunization and at 7 days after microinjection, the auditory function and the level of specific anti-KLH antibodies in the ser-um were measured by auditory brainstem response ( ABR) audiometry and ELISA, respectively.Seven days after microinjection, 3 ani-mals in each group were subjected to HE staining and light microscopy, another 3 to fluoro-autography for realizing the situations of the inner ear transfected by the lentiviral vector, and the other 4 to measurement of the contents of microRNA-146a in the inner ear tissue. Results Compared with the baseline, immunization significantly increased the level of specific anti-KLH antibodies in the serum (0.09 ±0.01 vs 1.90 ±0.74 in the RLV group, 0.11 ±0.02 vs 2.20 ±0.75 in the ELV group, and 0.11 ±0.02 vs 2.10 ±0.64 in the surgery simulation control) as well as the average threshold of the ABRⅢwave (left ear 11.67 ±2.58 vs 61.67 ±5.16 and right ear 12.50 ±2.73 vs 60.00 ±4.47 in the RLV group;left ear 14.16 ±3.76 vs 64.33 ±9.17 and right ear 13.33 ±2.58 vs 60.83 ± 4.92 in the ELV group;left ear 15.83 ±3.76 vs 64.17 ±10.2 and right ear 15.00 ±5.47 vs 62.50 ±9.35 in the surgery simulation control) .The average threshold of the ABRⅢwave was decreased after local injection into the inner ear as compared with that after immunization, with no statistically significant difference between the ELV and surgery simulation control groups.Fluoro-autographic ob-servation showed that the main parts of the inner ear transfected with microRNA-146a recombinant lentiviruses were the spiral limbus, spiral ganglion afferent fibers, basal cells of the spiral ligament, Corti organ, and psalterial cords.The immune inflammatory reaction of the inner ear was significantly reduced in the RLV group as compared with the ELV and surgery simulation control groups, while the content of microRNA-146a in the inner ear tissue was obviously increased in the former group than in the latter two. Conclusion The microRNA-146a recombinant lentiviral vectors are widely distributed and transfected in the inner ear tissue after injected via the scala tympani.Injecting recombinant microRNA-146a lentiviral vectors into the inner ear can significantly reduce pathological damage and auditory dysfunction caused by inner ear immune inflammatory reaction.%目的：自身免疫性内耳病（ autoimmune inner ear disease， AIED）是目前临床上一部分可以有效治疗的内耳疾病，对其的研究工作具有重要的临床实际意义和实用价值，文中探讨microRNA-146a对免疫介导性内耳病（ immune-mediated inner ear disease， IMIED）的免疫调节作用、及其治疗效果。方法采用钥孔戚血蓝蛋白抗原在已致敏的豚鼠圆窗龛局部免疫，制成IMIED动物模型30只，按配对设计分为microRNA-146a重组慢病毒组、空载慢病毒对照组、模拟手术对照组3组。microRNA-146a重组慢病毒组：鼓阶内注射microRNA-146a重组慢病毒；空载慢病毒对照组：鼓阶内注射慢病毒空载体；模拟手术对照组：鼓阶内注射PBS溶液。分别于免疫前、免疫后和鼓阶注射1周后，测试听觉功能和血清抗KLH特异性抗体水平变化。鼓阶内注射后1周（ ABR试验后），每组3只动物行HE染色和光镜观察；另3只动物行荧光观察（慢病毒载体转染情况）；，4只动物并测试内耳局部组织microRNA-146a的含量及其变化。结果3组动物免疫后血清中特异性抗KLH抗体水平较免疫前升高，重组慢病毒载体组[（1．90±0．74） vs （0．09±0．01），P＜0．05]，空载体对照组[（2．20±0．75） vs （0．11±0．02），P＜0．05]，模拟手术组[（2．10±0．64） vs （0．11±0．03），P＜0．05]。与免疫前对应耳比较，免疫后、鼓阶注射后ABRⅢ波平均阈值均增加（P＜0．05）；与免疫后对应耳比较，重组慢病毒载体鼓阶内注射后ABRⅢ波平均阈值降低（P＜0．05）。重组慢病毒载体组内耳microRNA-146a含量（1290．0±660．0）较空载体对照组（369．5±73．9）和模拟手术组（476．6±148．0）明显升高，差异有统计学意义（P＜0．05）。荧光观察显示：micro-RNA146a重组慢病毒载体在内耳中分布在骨螺旋唇、螺旋神经节传入纤维、螺旋韧带基底细胞、Corti器、血管纹等，内耳光镜观察显示内耳免疫炎性反应较空载慢病毒对照组和模拟手术对照组明显减轻。结论 micro-RNA146 a重组慢病毒载体经鼓阶注射到内耳后，可在内耳广泛分布和转染，内耳组织中mi-croRNA-146a的含量明显升高。重组micro-RNA146a慢病毒载体内耳导入可显著减轻内耳免疫炎性病理损伤和听觉功能障碍。
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