铁必复颗粒治疗老年性聋的临床疗效与分子机制研究

目的观察铁必复颗粒治疗老年性聋的临床疗效，通过实验探讨该方对肾虚耳聋治疗作用的分子机制。方法老年性聋患者136例，随机分两组，铁必复颗粒组70例（138耳），西药对照组66例（129耳），前者接受铁必复颗粒冲服，后者口服尼莫地平等。实验研究选用Wistar大鼠120只，随机分为两组。正常对照大鼠组，喂标准饲料16W；缺铁大鼠组，采用缺铁饲料喂养8W后，再分成肾虚耳聋组、铁必复颗粒组，肾虚耳聋组继续喂以缺铁饲料8W，铁必复颗粒治疗组喂以添加铁必复颗粒的缺铁饲料8W。取大鼠耳蜗膜性组织进行蛋白质组学分析，比较各组蛋白质表达差异。结果老年性聋患者铁必复颗粒组显效21耳，有效42耳，有效率45．65％；西药对照组有效10耳，有效率7．75％，前者有效率高于后者，两组疗效差异有统计学意义（P〈0．01）。实验研究表明，肌动蛋白、肌球蛋白、细胞骨架蛋白等在铁必复颗粒治疗组耳蜗膜性组织中高表达，与正常组和肾虚耳聋组相比，蛋白表达都有上调。铁必复颗粒组出现特异性高表达46kDaprotein、48kDaprotein等尚未命名的蛋白。结论铁必复颗粒治疗老年性聋有效，其作用机制可能与调控耳蜗肌动、肌球、细胞骨架蛋白等的表达水平有关。

Clinical effectiveness of Tiebifu Granule in the treatment of presbycusis and its molecular mechanism in experimental study

Objective To observe the clinical effectiveness of Tiebifu Granule in the treatment of presbycusis and its molecular mechanism in experimental study. Methods Clinical data of 136 patients with presbycusis were randomly divided into two groups. In group of Tiebifu Granule, 70 patients （138 ears） were medicationed by Tiebifu Granule. In control group of western medicine, 66 patients （129 ears） were given vitamin B6, nimodipine, etc. In experimental study, 120 Wistar rats with no ear disease were randomly divided into two groups. The rats of normal control group were fed with normal dietary for 16 weeks. The rats of experiment group were fed with iron deficiency diet for 8 weeks to make iron deficiency hearing loss models that ABR threshold raising ≥ 15dB at least in one ear. They were then divided into 2 groups. In group of Shenxu-hearing loss, the animals were fed with iron deficiency diet for another 8 weeks. The rats of Tiebifu Granule group were fed with iron deficiency diet plus Tiebifu Granule for 8 weeks. The proteins of cochlea were examined to find the differences and to search for proteomic profile using BIOWORKS software. Results Among the 138 affected ears in 70 patients treated by Tiebifu Granule, and 129 affected ears in 66 patients in the control group treated by western medi- cine, the total effective rates were 45.65 % and 7.75 %, respectively. The significant difference in the rates of effectiveness was found between the above two groups. The results of experimental study showed that actin, aortic smooth muscle; actin, cytoplasmic 1 ; isoform 1 of titin were significantly up-regulated in Tiebifu Granule group as compared to Shenxu-hearing loss group and normal controls. The higher cover percent and specific up-regulated 46 kDa protein, 48 kDa protein and other new proteins were found in the Tiebifu Granule group. Conclusion The effectiveness of Tiebifu Granule in the treatmerit of presbycusis is observed in clinical data, which molecular mechanism maybe linked with the expression levels of actin, myosin, titin and cochlin precursor in cochlea.