围绝经期向心性肥胖是与下丘脑AgRP神经元过度活化相关的脂肪组织稳态失衡病征，增加急慢性疾病风险。研究显示，肠道微生物结构紊乱可促进下丘脑AgRP神经元过度活化，提示调控“微生物-肠-脑轴”是维持脂肪组织稳态的新思路。中医学认为“肝肾阴虚”是该病主要病机，前期证实补益肝肾方“二至丸”可改善肠道微生物结构、减少白色脂肪过度堆积，但其深入机制未明。据此提出假说：提升肠道产生短链脂肪酸的微生物含量，抑制下丘脑AgRP神经元过度活化，进而提高能量代谢，是该方发挥作用的潜在机制。拟以去卵巢向心性肥胖小鼠为模型、胃饥饿素激活AgRP神经元为研究对象，观察二至丸在体通过“资脾气”而提升短链脂肪酸含量、“养脑神”而调控AgRP神经元活化水平，离体研究其具体作用靶点，最终阐明二至丸改善“微生物-肠-脑轴”功能以提高能量代谢，治疗围绝经期向心性肥胖的作用靶点与机制，为临床提供实验依据，并拓展补益肝肾理论内涵。

Perimenopausal central obesity is an imbalance of adipose tissue homeostasis closely related to excessive AgRP neuronal activation in hypothalamus, increasing the risk of acute and chronic diseases. The research showed that the disorder of gut microorganism could induce the over activation of AgRP neurons in hypothalamus. It was suggested that the regulation of microbiot-gut-brain axis would be a new idea to maintain the steady state of adipose tissue. “Yin deficiency of liver and kidney” is its main pathogenesis. Previous studies have confirmed that Erzhi Pill could improve gut microbiota and reduce the centripetal accumulation of white adipose, but the underlying mechanism has not been explained. Therefore, the hypothesis was put forward that “ increasing the amount of microbes in the gut that producing short-chain fatty acids, inhibiting the over activation of AgRP neurons in the hypothalamus and improving the energy metabolism will be the potential mechanism of this prescription”. We intend to replicate the ovariectomized mice with centripetal obesity and the AgRP neurons activated by ghrelin as the research object to observe whether Erzhi Pill increase the SCFAs by aiding spleen qi, and regulate AgRP neuron activation levels by nourishing brain spirit. And we will take vitro experiments to study its specific targets. Finally, we clarify the target and mechanism of Erzhi Pill in improving energy metabolism in the treatment of perimenopausal centriolar obesity based on improving microbiot-gut-brain axis’ function , which can provide clinical experimental basis and expand the theoretical connotation of tonifying liver and kidney.