基于SCFAs介导的组蛋白乙酰化与GH-IGF1轴研究温肾通督方调节肠道微生态促进脊髓损伤修复的作用机制

根据脊髓损伤“督脉受损、脏腑受累”的病机，我们构建了温肾通督方，前期研究表明其确切疗效与上调胰岛素样生长因子1（IGF1）水平、调控小胶质细胞活化有关，但具体机制仍欠清晰。我们通过进一步研究又发现温肾通督方能调节肠道微生态，而短链脂肪酸（SCFAs）作为肠道微生物的代谢产物，可以影响脊髓损伤后的运动功能，并与神经细胞组蛋白乙酰化、生长激素（GH）-IGF1轴介导的小胶质细胞活化有关。由此，我们提出科学假说：温肾通督方可调节SCFAs的含量，进而通过调控GH-IGF1轴、组蛋白乙酰化上调IGF1水平，协同激活小胶质细胞，促进脊髓损伤修复。本项目拟通过代谢组学技术检测SCFAs含量，宏基因组学技术分析温肾通督方对肠道微生物组成与功能的调节作用，检测组蛋白乙酰化水平，评估GH-IGF1轴活力，寻找调节肠道微生态治疗脊髓损伤的候选靶点，从另一层面探索温肾通督方“通督脉、调脏腑”的作用机制。

Wenshen Tongdu Prescription is designed according to the pathogenesis of spinal cord injury, which is Du Meridian and viscera damage. Previous studies have shown that its curative effect is related to up-regulation of insulin-like growth factor 1 (IGF1) and regulation of microglia activation. However, the mechanism remains unclear. Through further research, we found that Wenshen Tongdu Prescription can regulate intestinal microecology, and short-chain fatty acids (SCFAs), as metabolites of intestinal microbes, can affect motor function after spinal cord injury. SCFAs are also involved in histone acetylation in nerve cells, growth hormone (GH)-IGF1-axis-mediated microglia activation. Therefore, we propose a scientific hypothesis: Wenshen Tongdu Prescription can change the content of SCFAs, and then up-regulates IGF1 level by regulating the GH-IGF1 axis and histone acetylation, synergistically activates microglia, and promotes spinal cord injury repair. This study intends to detect the content of SCFAs by metabolomics technology. The regulation of microbiota by Wenshen Tongdu Prescription will be analyzed by metagenomics. The level of histone acetylation and activity of GH-IGF1 axis will also be detected. We hope to find a candidate gene target for spinal cord injury treatment by regulating intestinal microecological, and explore the mechanism of spinal cord injury treatment by Wenshen Tongdu Prescription from another level.