Pyruvate kinase M2 (PKM2) improve symptoms of post-ischemic stroke depression by activating VEGF to mediate the MAPK/ERK pathway

丙酮酸激酶 M2 (PKM2) 通过激活 VEGF 介导 MAPK/ERK 通路改善缺血性中风后抑郁症的症状

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作者:Yun Feng, Xuebin Li, Jie Wang, Xiaohua Huang, Lanqing Meng, Jianmin Huang

Conclusion

PKM2 improves symptoms of post-ischemic stroke depression by activating VEGF-mediated MAPK/ERK pathway.

Methods

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.

Purpose

To evaluate and identify the effects and explore the mechanisms of pyruvate kinase M2 (PKM2) on stroke-induced post stroke depression (PSD).

Results

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.

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