肠道菌群通过次生代谢调控心血管老化的机制研究

心血管年龄是机体年龄的真实体现，肠道菌群可能在衰老中发挥关键作用，短链脂肪酸(SCFA)是菌群产生的次生代谢物。我们前期研究表明，机体衰老过程伴随着肠道菌群的老化及SCFA的减少，老年菌群移植可以导致小鼠发生心血管老化、内皮功能不良、高血压易感、血管壁纤维化增加、平滑肌层增厚，伴随着SCFA减少及LKB1-AMPK-自噬信号抑制。本研究拟在前期基础上，绘制菌群-SCFA-心血管老化的增龄性变化动态图谱，寻找衰老早期阶段的关键调节子，应用无菌鼠模型、菌群移植、宏基因组学、功能代谢组学、组织特异性敲除小鼠、分子心脏病学等方法研究肠道微生态和细胞内外环境稳态，重点阐明肠道菌群-SCFA通过LKB1-p21和AMPK-自噬信号通路调控心血管自噬/老化平衡和机制；使用青年菌群和单一菌移植防治衰老，并探寻新的治疗方法。

The degree of cardiovascular aging represents the true age of the body. The gut microbiota may play a key role in aging and short-chain fatty acids (SCFAs) are secondary metabolites produced by the microbiota. Our previous studies have shown that the aging process of the human body is accompanied by the aging of the gut microbiota and the reduction of SCFA. The transplantation of elderly microbiota can lead to cardiovascular aging, endothelial dysfunction, sensitivity to hypertension, increased fibrosis of the vascular wall and thickening of the smooth muscle layer. At the same time, it is accompanied by the reduction of SCFA and the inhibition of LKB1-AMPK autophagy signal. This study aims to draw a dynamic map of the aging changes of the microbiota-SCFA-cardiovascular aging on the basis of previous studies to discover the key regulatory factors of early aging, and apply germ-free mouse model, microbiota transplantation, metagenomics, functional metabolomics, tissue-specific knockout mice, molecular cardiology and other methods to study intestinal microecology and homeostasis of the internal and external cellular environment. We are committed to elucidating the mechanism by which the gut microbiota-SCFA regulates cardiovascular autophagy/aging balance through the LKB1-p21 and AMPK autophagy signaling pathways. We use youth microbiota and single bacterial transplantation to prevent aging and explore new treatment methods.