Department of Neurology, The Affiliated Hospital of Youjiang Medical University for Nationalities, Baise City, Guangxi Province, China.
Department of Neurology, Youjiang Medical College for Nationalities, Baise City, Guangxi Province, China.
Brain Behav. 2022 Jan;12(1):e2450. doi: 10.1002/brb3.2450. Epub 2021 Dec 13.
To evaluate and identify the effects and explore the mechanisms of pyruvate kinase M2 (PKM2) on stroke-induced post stroke depression (PSD).
Rats were separated into six different groups, including sham + saline, Stroke + saline, PSD + saline, PSD + recombinant pyruvate kinase M2 (rPKM2) (112 ng/kg), PSD + rPKM2 (224 ng/kg), and PSD + rPKM2 (224 ng/kg) + bevacizumab. Then, the body weight, sucrose preference rate, immobility time, horizontal movement, and vertical movement were determined to evaluate the effect of PKM2 on improving the depressive behavior of PSD rats. Subsequently, the proliferation of oligodendrocytes in subventricular zone (SVZ) of rats in each group was examined by western blot and immunofluorescent staining. Furthermore, the mRNA and protein expression levels of TNF-α, IL-6, and IL-1β were also detected by qPCR and ELISA to verify the anti-inflammatory effects of PKM2 on PSD rats. In addition, the protein expression levels of MDA, LDH, and NO were tested to reveal that PKM2 can reduce oxidative stress in PSD rats. The western blot and IHC assays were employed to examine the protein expression levels of VEGF, PKM2, and ERK in PSD rats.
In this study, the results showed that PKM2 can improve the depressive behavior and proliferation of oligodendrocytes in PSD rats. In addition, PKM2 has anti-inflammatory and anti-oxidative stress effects on PSD rats. Meanwhile, PKM2 activated the expression level of VEGF/MAPK/ERK pathway.
PKM2 improves symptoms of post-ischemic stroke depression by activating VEGF-mediated MAPK/ERK pathway.
评估和确定丙酮酸激酶 M2（PKM2）对缺血性脑卒中后抑郁（PSD）的影响，并探讨其机制。
将大鼠分为六组，分别为假手术+生理盐水组、脑卒中+生理盐水组、PSD+生理盐水组、PSD+重组丙酮酸激酶 M2（rPKM2）（112ng/kg）组、PSD+rPKM2（224ng/kg）组和 PSD+rPKM2（224ng/kg）+贝伐单抗组。然后，通过测量体重、蔗糖偏好率、不动时间、水平运动和垂直运动来评估 PKM2 改善 PSD 大鼠抑郁行为的效果。接着，通过 Western blot 和免疫荧光染色检测各组大鼠侧脑室下区（SVZ）中少突胶质细胞的增殖。此外，通过 qPCR 和 ELISA 检测 TNF-α、IL-6 和 IL-1β 的 mRNA 和蛋白表达水平，以验证 PKM2 对 PSD 大鼠的抗炎作用。另外，还检测了 MDA、LDH 和 NO 的蛋白表达水平，以揭示 PKM2 可以减轻 PSD 大鼠的氧化应激。Western blot 和 IHC 检测用于评估 PSD 大鼠中 VEGF、PKM2 和 ERK 的蛋白表达水平。
本研究结果表明，PKM2 可改善 PSD 大鼠的抑郁行为和少突胶质细胞增殖。此外，PKM2 对 PSD 大鼠具有抗炎和抗氧化应激作用。同时，PKM2 激活了 VEGF/MAPK/ERK 通路的表达水平。
PKM2 通过激活 VEGF 介导的 MAPK/ERK 通路改善缺血性脑卒中后抑郁症状。
