目前，我国重金属铅污染形势十分严峻，铅中毒可以引起或加重人类的听力障碍。本课题组前期实验发现铅暴露可以引起新生大鼠耳蜗螺旋神经元（SGN）凋亡，而对基底膜的内外毛细胞无明显破坏作用，其具体机制不详；同时，本课题组前期用羟基磷灰石纳米颗粒（nHAT）作为内耳基因治疗载体的研究取得多项阶段性进展。本项目拟在前期研究基础上，通过观察铅暴露所致SGN损伤过程中凋亡、氧化应激及自噬相关基因和蛋白的差异性表达从而揭示SGN铅毒性损伤的可能机制；并观察长期铅暴露对大鼠听力的具体影响及铅暴露与SGN损害程度的相关性分析；进一步在体内外实验中应用改良型nHAT载体介导相关治疗基因转染SGN，评估载体-基因复合物在SGN中的转染效率及对SGN铅毒性损伤的保护作用。

At present, the situation of heavy metal (lead) pollution in China is very serious, and the lead poisoning can cause or aggravate human hearing disorders. Our previous studies found that lead exposure can induce neonatal rats' cochlear spiral ganglion neurons (SGN) apoptosis, but neither inner hair cells nor outer hair cells in cochlear basilar membrane appeared obvious damage. However, the detailed mechanism is not clear. Besides, the studies on hydroxyapatite nanoparticles (nHAT) as a gene vector for inner ear gene therapy has made many progress in our group. Based on the previous studies, this project will observe the differential expression of related genes of apoptosis, oxidative stress and autophagy in SGN after lead exposure by means of RT-PCR array and western blot, in order to reveal the probable mechanism of SGN injury induced by lead exposure. This project will also investigate the effect of long-term lead exposure on hearing function of rats and analyze the relationship between lead exposure and SGN damage. Meanwhile, we will transfect the therapeutic genes mediated by modified nHAT into SGN in vivo and in vitro, in order to assess transfection efficiency of vector-gene compound in SGN and protective effect of transfection on lead-induced SGN injury.