上转换纳米颗粒介导的光动力疗法修复大鼠脊髓损伤的研究

Treatment of spinal cord injury(SCI) has become a worldwide problem.Studies have shown that glial scar formation after spinal cord injury significantly impede axonal regeneration and functional recovery.Therefore, how to reduce the glial scar after SCI has become the hot point.Lots of foreign studies have confirmed that x-ray radiation therapy can be effective in reducing glial scar formation after SCI.But the inaccurate target localization and related side effects limited its clinical application.In recent years, photodynamic therapy is concerned, it is mainly used in the treatment of various malignant tumor and the disease such as arthritis,acne ect.In this study,photodynamic therapy is introduced for the treatment of spinal cord injury.To solve the problem of insufficient tissue penetration depth of the emission light,we combined the photodynamic therapy with upconversion nanoparticle to prepare a new type of upconversion nanoparticle. In vitro, MTT detection,cytochrome c release test ect will be applied to observe its killing effect when co-culturing with astrocytes. Then,such particles will be injected into the surrounding area of the lesion site of the injured spinal cord. BBB score and footprint analysis will be used for the observation of function recovery of the injured rats, HE and GFAP staining for glial scar size, GAP-43 dye, BDA neural tracing, nerve electrophysiological examination and electron microscopic observation ect for axonal regeneration and finally we hope our research will provide a new idea for the clinical treatment of spinal cord injury in the future.

脊髓损伤的治疗一直是世界性难题。研究表明，胶质瘢痕的形成极大程度阻碍了损伤轴突的再生和功能恢复。因此，如何减少脊髓损伤后胶质瘢痕的形成已成为目前研究的热点。国外研究证实，X线放疗可以有效的减少脊髓损伤后胶质瘢痕形成。但其难以精确的靶向定位和相关副作用限制了其临床应用。近年来，光动力疗法备受关注，它主要用于治疗多种恶性肿瘤以及关节炎、痤疮等疾病。本研究将光动力疗法引入治疗脊髓损伤。为解决其发射光组织穿透深度不足的问题，我们将其与上转换纳米颗粒相结合制备出新型上转换纳米颗粒。在体外运用MTT检测、细胞色素C释放试验等方法观察其对星形胶质细胞的杀伤作用。然后将此种颗粒注射到大鼠脊髓损伤区周围，用BBB评分，脚印分析观察大鼠行为功能恢复，HE和GFAP染色观察胶质瘢痕大小，GAP-43染色、BDA神经示踪，神经电生理检查及电镜观察等方法观察损伤轴突再生情况，进而为临床治疗脊髓损伤提供新的思路。

脊髓损伤的治疗一直是世界性难题。研究表明，胶质瘢痕的形成极大程度阻碍了损伤轴突的再生和功能恢复。因此，如何减少脊髓损伤后胶质瘢痕的形成已成为目前研究的热点。国外研究证实，X线放疗可以有效的减少脊髓损伤后胶质瘢痕形成。但其难以精确的靶向定位和相关副作用限制了其临床应用。近年来，光动力疗法备受关注，它主要用于治疗多种恶性肿瘤以及关节炎、痤疮等疾病。本研究将光动力疗法引入治疗脊髓损伤。为解决其发射光组织穿透深度不足的问题，我们将其与上转换纳米颗粒相结合制备出新型上转换纳米颗粒。在体外运用MTT检测、细胞色素C释放试验等方法观察其对星形胶质细胞的杀伤作用。然后将此种颗粒注射到大鼠脊髓损伤区周围，用BBB评分，脚印分析观察大鼠行为功能恢复，HE和GFAP染色观察胶质瘢痕大小，GAP-43染色、BDA神经示踪，神经电生理检查及电镜观察等方法观察损伤轴突再生情况，进而为临床治疗脊髓损伤提供新的思路。