晚发型抑郁症（LOD）是常见的老年病，极易发展为老年痴呆症，严重影响老年人的生活质量并加剧患者家庭和社会的负担。认知功能损害是增加LOD治疗难度的主要原因之一。本课题以认知功能损害为切入点，从“脉络丛（CP）衰老—叶酸脑转运—海马神经发生—认知功能”这一新视角，提出“补肾治法方药可通过改善CP衰老，增强叶酸脑转运，促进海马神经发生，进而修复认知功能，发挥其整体有效的抗LOD效应”的科学假说。通过整体实验和体外实验，探讨补肾治法方药二仙汤对LOD大鼠CP结构与功能、叶酸脑转运、海马DG区神经干细胞增殖分化的影响，阐明中医补肾治法方药发挥整体有效抗LOD效应的作用靶点及机理。本研究不仅对中医“肾—脑髓体系”理论有所丰富和创新，而且也是对补肾治法方药在老年性精神疾病防治中的创新运用。本研究亦将为今后补肾治法方药防治 LOD的转化医学研究提供科学依据。

Late-onset depression(LOD)is a common senile disease with higher risk of dementia, which seriously affects the life quality of the elderly people and aggravates the burden of both family and society. Cognitive function impairment is one of the main reasons for increasing the difficulty of LOD treatment. Taking the cognitive function impairment as the breakthrough point, from a new perspective of "Plexus choroid(CP) aging-Folate's brain transport-Hippocampal neurogenesis- Cognitive function", we put forward the scientific hypothesis: "kidney-tonifying therapy and prescription could exert effective and integral anti-LOD effects by improving CP aging, enhancing folate's brain transporter, promoting hippocampal neurogenesis and repairing cognitive function. By in vivo and in vitro experiments, in LOD model rats, the effects of kidney-tonifying therapy and prescription(Erxiantang) on structure and function of CP, folate's brain transporter and the stem cell proliferation and differentiation in DG area of hippocampus were investigated, thereby clarifying the targets and mechanisms of anti LOD effects of kidney-tonifying therapy and prescription. The study would not only enrich and innovate of the theory of "kidney-brain system" in traditional Chinese medicine, but also innovatively apply kidney-tonifying therapy and prescription into prevention and treatment of mental illness in the elderly people. The study is helpful to further clarify and reveal the scientific value, characteristics and advantages of kidney-tonifying therapy and prescription in prevention and treatment of mental disease. In addition, the study would provide scientific evidence for translational medicine research on kidney-tonifying therapy and prescription in the prevention and treatment of LOD.