中文摘要
氨基糖甙类抗生素(AmAn)耳毒性聋病机复杂,迄今尚未明了,防治甚为棘手,是因聋致残常见原因。以补肾健脾、活血通窍为治法的复方聪耳剂是我们临床治疗后天性感音神经性耳鸣耳聋有效验方,前期动物研究表明,它具有延缓老年性耳蜗毛细胞、螺旋神经节神经元凋亡的作用,其中部分药物具有拮抗庆大霉素耳毒性聋的作用,但原方及拆方对比作用与机制仍不清楚。据此提出假说:原方从脾肾瘀论治对抗AmAn耳毒性优于拆方从肾或从脾论治,同时通过优势治法干预研究,探明相关因子的调控影响。鉴此,我们将利用耳蜗器官体外培养建立的AmAn耳毒性动物模型、配合在体模型,采用免疫组化、多重免疫荧光、PCR等为主的分子生物学技术,结合耳蜗铺片、耳蜗切片等方法,按照中医不同治则,对复方聪耳剂及其拆方进行比较,同时探讨相关因子调控影响,从分子、细胞等水平揭示其作用和机制,这对于验证中医理论,优化组方,指导临床用药,开发新药均具有重大意义。
英文摘要
Aminoglycoside antibiotics ( AmAn ) ototoxic mechanism is very complex, and many aspects of them is not yet clear, so prevention on the ototoxicity is very difficult. It was common reason of deafness and then disability induced by AmAn. Cong-er preparation of Chinese herbal compound based on the treating rules of Bushen-Jianpi-Huoxuetonqiao of TCM is our clinical effective prescription in treating sensorineural tinnitus and deafness. Previous animal experiments showed it could delay the apoptosis of age-related cochlear hair cells and spiral ganglion neuron, some herbal of them had also antagonism on gentamicin ototoxicity. By said above, we put forward the hypothesis: treating rule with Bushen-Jianpi-Huoxuetonqiao from the original prescription in resisting AmAn ototoxicity may be better than treating rule with Bushen- Huoxue, Jianpi- Huoxue from its disassembled prescriptions, at the same time, by the research in intervention of the dominant treating rules, ascertain influence of related factors regulation. To test and verify this hypothesis, through take animal AmAn ototoxic model in vitro based on the cochlear organic culture or in vivo, use molecular biology technology in immunohistochemistry, multiple immunofluorescence ,PCR, combine with the methods of cochlea preparation and cochlea section, the treating effect on the compound of TCM and its disassembled prescriptions will be compared according to TCM different treating rule, meanwhile, explore related factors regulating effects, reveal TCM effects and mechanism from cell level to molecular level. It is of great significance for verifying the meaning of TCM theoretical guidance, optimizing prescription, guiding clinical drugs use and developing new drugs.
