中文摘要
线粒体产能是脾主运化的重要环节之一。研究发现,应激刺激极易诱发线粒体基因突变,导致异常蛋白聚积和自由基大量产生,损伤线粒体。但细胞可通过线粒体动力学对抗基因突变,上调Lon蛋白酶降解异常蛋白,增强线粒体自噬以清除损伤线粒体,本研究称之为线粒体动力学-Lon蛋白酶-自噬机制。研究显示,脾气虚时多种细胞的线粒体出现基因突变、结构损伤和功能紊乱,原因不明。前期工作发现,脾气虚大鼠空肠和心肌细胞线粒体内出现蛋白聚积;胃和空肠Lon蛋白酶表达上调;海马和下丘脑神经元线粒体损伤,但基础自噬减弱。据此提出,脾气虚的发生与线粒体动力学-Lon蛋白酶-自噬机制紊乱有关。为证明假说,本项目以大鼠为对象,主要采用电镜和分子生物学技术,通过检测线粒体的结构和基本功能,评估相关细胞的脾气虚参与度,探讨脾的细胞定位,进而从线粒体动力学、Lon蛋白酶表达和自噬等方面研究脾气虚的发生机制,为揭示脾的科学内涵奠定基础。
英文摘要
Mitochondrial producing energy is one of the important links of spleen governing transportation and transformation. Studies find that, stress stimuli easily induce mitochondrial DNA (mtDNA) mutation, resulting in the accumulation of abnormal proteins and free radical production, damaging mitochondria. However, mitochondrial dynamics can opposite mtDNA mutation, Lon protease hydrates abnormal protein and mitophagy rids of dysfunctional mitochondria in cells, and these activities are combined termed the mitochondrial dynamics-Lon protease-mitophagy machinery in this study. Reports show that there are mtDNA mutation and mitochondrial dysfunction in varied cells in spleen qi deficiency, but its mechanism is unknown. Our preliminary works found that, in rats of spleen qi deficiency, abnormal protein aggressed in mitochondria of myocardiac and jejunum cell, Lon protease expressions in stomach and jejunum were increased, the mitochondrial structure was damaged and basal mitophagy was reduced in hippocampal and hypothalamic neurons. Thereby, it is presumed that the dysfunction of the mitochondrial dynamics-Lon protease-mitophagy machinery in related cells implicates the development of spleen qi deficiency. To prove this hypothesis, rats will be used in the study to valuate the related cellular engagements in spleen qi deficiency according to alternations of mitochondrial structure and basal functions, attempting to explore the cellular location of spleen, and then study changes of mitochondrial dynamics, Lon protease expression and mitophagy, trying to detect the mechanism of spleen qi deficiency. We hope that this study can lay foundation for revealing the essence of spleen.
