基于“肾-脑-目”系统探讨肾阳虚证对实验性近视豚鼠发病的影响及分子机制

China has the highest prevalence rate of juvenile myopia in the world. And the high rate of myopia has become a major social and scientific issue in recent years. Clinical results show that Traditional Chinese Medicine is effective in preventing and treating myopia. TCM theory argues that the pathogenesis of myopia is related to Yang deficiency and liver and kidney deficiency, and “kidney - brain - eye "is closely linked, the vision of the eye is produced by the brain, whose root is kidney. Its biological mechanism is not clear although. Many studies have shown that adolescent myopia patients are accompanied by kidney deficiency, and the visual center of the brain is strongly related to the occurrence and development of myopia. In our previous study, we successfully constructed a kidney-Yang deficiency syndrome myopic animal model and found that kidney-Yang deficiency syndrome affects the process of myopia through remodeling the thickness of posterior sclera of lens-induced myopia guinea pigs. And on the base of that, this study is proposed to detect the expression of neurotransmitters such as GABA and their receptors in the visual cortex of the brain and retina, and the expression of MMP-2 and its inhibitor TIMP-2 in the sclera to explore the molecular mechanism of Kidney-Yang deficiency syndrome on myopic guinea pigs induced by lens; and study the impact of bushen medicine and acupuncture intervention on progress of myopia in lens-induced myopia kidney-yang deficiency guinea pigs to clear the causal relationship of kidney-yang deficiency, brain and myopia. This study is to finally clarify the effects and molecular mechanism of "Kidney - brain - eye" system in the pathogenesis of myopia. It would be helpful for providing new ideas for preventing and treating myopia in the future.

我国是青少年近视患病率最高的国家，近视已成为重大的社会与科学问题。临床结果显示：中医防治近视疗效显著。中医理论认为，“肾-脑-目”密切联系，明确地将眼的视觉归结于肾精所生之脑，然其生物学机制尚不清楚。近视的基本病机是阳气不足和肝肾亏虚，研究显示，青少年近视患者多见肾虚体质，且大脑视觉中枢对近视的发生发展有重要影响。本项目在前期研究中已构建肾阳虚动物近视模型，发现肾阳虚体质通过影响负透镜诱导豚鼠的巩膜重塑使其近视程度加深，现拟在此基础上，通过分析大脑视皮层和视网膜中神经递质GABA等因子及其受体表达的变化规律，并检测巩膜中MMP-2及其抑制因子TIMP-2的表达变化，探讨关键因子的变化与近视发病的关系；使用补肾药和针刺的方法进行干预，观测其对近视发病的作用效果和作用机制，明确其因果关系，最终阐明“肾-脑-目”系统在近视发病中的作用及其机制，为今后青少年近视防控提供新的思路。

我国是青少年近视患病率最高的国家，近视已成为重大的社会与科学问题。中医理论认为，“肾-脑-目”密切联系，明确地将眼的视觉归结于肾精所生之脑，然其生物学机制尚不清楚。本项目联合利用氢化可的松腹腔注射法和负透镜诱导法构建肾阳虚近视豚鼠模型，分别采用针刺肾俞穴和金匮肾气丸水煎剂灌胃的方法对肾阳虚近视动物进行干预，结果显示肾阳虚近视动物近视程度更深，眼轴更长，而针刺肾俞穴和金匮肾气丸均可通过改善肾阳虚近视动物体质有效延缓其近视发展程度，使视网膜双调蛋白表达降低，眼轴生长减缓，且这一变化与脑、眼组织中的多巴胺、GABA等神经递质及受体表达水平变化有关。这一结果提示我们应重视青少年体质的变化，通过及时调合偏颇体质可以有效阻抑中低度近视向高度近视发展，从而避免高度近视伴发的各类并发症的发生，为我国近视防控提供了新的思路。