MST4 激酶抑制剂 Hesperadin 通过脑内出血小鼠中的 MST4/AKT 通路减弱自噬和行为障碍。

MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice.

机构信息

Key Laboratory of Noncoding RNA Transformation Research of Anhui Higher Education Institution (Wannan Medical College), The First Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.

Department of Neurology, The Second Affiliated Hospital of Wannan Medical College, Wuhu, 241000 Anhui, China.

出版信息

Behav Neurol. 2020 Feb 3;2020:2476861. doi: 10.1155/2020/2476861. eCollection 2020.

BACKGROUND

The aim of this study was to explore the role of hesperadin in intracerebral hemorrhage (ICH) mice, with the involvement of the mammalian ste20-like kinase 4 (MST4)/AKT signaling pathway.

METHODS

All mice were divided into four groups: sham group, sham+hesperidin group, ICH group, and ICH+hesperadin group. The effects of hesperadin were assessed on the basis of brain edema and neurobehavioral function. Furthermore, we observed MST4, AKT, phosphorylation of AKT (pAKT), and microtubule-associated protein light chain 3 (LC3) by western blotting. Protein localization of MST4 and LC3 was determined by immunofluorescence.

RESULTS

The expression of MST4 was upregulated at 12 h and 24 h after ICH. Brain edema was significantly decreased and neurological function was improved in the hesperadin treatment group compared to the ICH group ( < 0.05). Hesperadin decreases the expressions of MST and increases pAKT after ICH. Autophagy significantly increased in the ICH group, while hesperadin reduced this increase.

CONCLUSION

Hesperadin provides neuroprotection against ICH by inhibiting the MST4/AKT signaling pathway.

背景

本研究旨在探讨 hesperadin 在脑出血（ICH）小鼠中的作用，涉及哺乳动物 STE20 样激酶 4（MST4）/AKT 信号通路。

方法

所有小鼠分为 4 组：假手术组、假手术+hesperadin 组、ICH 组和 ICH+hesperadin 组。基于脑水肿和神经行为功能评估 hesperadin 的作用。此外，我们通过 Western blot 观察 MST4、AKT、AKT 磷酸化（pAKT）和微管相关蛋白轻链 3（LC3）的表达。通过免疫荧光法确定 MST4 和 LC3 的蛋白定位。