中文摘要
早期糖尿病视网膜病变包括神经病变与血管病变,且神经病变可能早于并加剧血管病变的发生。然而现有的治疗方式大多靶向血管病变且疗效有限。从“气血亏虚,血瘀络阻”的病机角度出发,我们发现当归补血汤加味方(RRP)可有效缓解早期糖尿病视网膜的血管病变。基于“多靶向,多机制”的复方特点,RRP能否改善神经病变从而更早更全面地缓解该疾病呢?预实验发现:RRP可缓解糖尿病视网膜神经节细胞(RGC)损伤及其内质网应激(ER stress)的激活;抑制ER stress可缓解缺氧引起的RGC凋亡,提示RRP可能通过抑制ER stress介导的RGC损伤改善糖尿病视网膜病变。本课题计划运用I型糖尿病大鼠模型和RGC-5细胞缺氧诱导模型深入阐明ER stress介导RGC凋亡的上下游分子机制及RRP的作用靶点,为早期糖尿病视网膜病变治疗和RRP的运用提供新的科学依据。
英文摘要
Microvascular and neural dysfunction are hallmarks of Diabetic retinopathy (DR), in which neural dysfunction may occur earlier and exacerbate microvascular dysfunction. So far, most treatments for DR are targeting microvascular dysfunction, however, with limited effects indicating that more attention for neural dysfunction are required. Based on Chinese traditional medicine theory, we proposed and proved that an aqueous extract of Radix Astragali, Angelica sinensis, and Panax notoginseng (RRP) was protective in preventing vascular lesions in DR. Of note, our preliminary data suggested that RRP could prevent not only vascular lesions but also retinal ganglion cell (RGC) lesions in DR, together with ER stress inhibition. Inhibition of ER stress could ameliorate hypoxia induced RGC apoptosis. These results indicated that RRP could possibly ameliorate DR progress by preventing ER stress mediated RGC lesions. Thus, we proposed a further investigation on the underlying molecular mechanisms mediating ER stress effect on RGC apoptosis as well as the molecular targets of RRP treatment in STZ induced type 1 diabetic animal model and hypoxia stimulated RGC-5 culture model. This study will help to elucidate the mechanisms and therapy potentials of RRP application on DR.
