血管紧张素II及血管紧张素（1-7）对肝星状细胞自噬的调控：肝纤维化的新机制

Autophagy is hot research area resulting in liver fibrosis. Excessive production of reactive oxygen species can promote the occurrence of hepatic stellate cells autophagy, which activates hepatic stellate cells. Angiotensin II (AngII) and angiotensin (1-7) (Ang(1-7)) are the new therapeutic targets of liver fibrosis. However, the regulation mechanism of AngII and Ang(1-7) on hepatic stellate cells autophagy remains unclear. Our previous research showed that AngII promoted the production of reactive oxygen species which could be reversed by Ang(1-7). Consequently, we hypothesize that AngII activates AMPK/TSC2/mTOR pathway by inducing reactive oxygen species production, leading to autophagy and hepatic stellate cells activation. At the same time, the effects can be inhibited by Ang(1-7). We prepare to observe the effects of AngII and Ang(1-7) on hepatic stellate cells oxidation, autophagy, activation, and AMPK/TSC2/mTOR pathway, and explore the mechanism of autophagy mediating the effects of AngII and Ang(1-7) on hepatic stellate cells in vivo and in vitro. Our research has important significance for improving the mechanism of Renin-Angiotensin System (RAS) regulating liver fibrosis, and provides a new strategy for the prevention and treatment of liver fibrosis.

自噬是目前致肝纤维化的研究热点。活性氧过度生成可以促进自噬的发生，肝星状细胞自噬可以促使其活化。血管紧张素II(AngII)和血管紧张素（1-7）(Ang(1-7))是目前肝纤维化治疗的新靶点，然而它们对肝星状细胞自噬的的调控机理仍未明确。我们前期研究发现，AngII可以促进肝脏活性氧的生成，Ang(1-7)可以抑制上述作用。因此我们设想：AngII通过促进活性氧的生成，激活AMPK/TSC2/mTOR通路，诱导肝星状细胞发生自噬进而促使其活化。同样，上述作用可以被Ang(1-7)抑制。本课题拟从体内外两个层面观察AngII与Ang(1-7)对肝星状细胞氧化、自噬、活化以及AMPK/TSC2/mTOR通路的影响，探究自噬介导AngII与Ang(1-7)对肝星状细胞调控的作用机制。本研究对于完善肾素-血管紧张素系统（RAS）调控肝纤维化的机理有重要意义，为肝纤维化的防治提供新策略。

自噬是目前致肝纤维化的研究热点。活性氧过度生成可以促进自噬的发生，肝星状细胞自噬可以促使其活化。血管紧张素II(AngII)和血管紧张素（1-7）(Ang(1-7))是目前肝纤维化治疗的新靶点，然而它们对肝星状细胞自噬的的调控机理仍未明确。我们的研究发现，AngII可以促进肝脏活性氧的生成，Ang(1-7)可以抑制上述作用。我们的结果证明：AngII通过促进活性氧的生成，激活AMPK/TSC2/mTOR通路，诱导肝星状细胞发生自噬进而促使其活化。同样，上述作用可以被Ang(1-7)抑制。本课题从体内外两个层面观察AngII与Ang(1-7)对肝星状细胞氧化、自噬、活化以及AMPK/TSC2/mTOR通路的影响，探究自噬介导AngII与Ang(1-7)对肝星状细胞调控的作用机制。本研究对于完善肾素-血管紧张素系统（RAS）调控肝纤维化的机理有重要意义，为肝纤维化的防治提供新策略。