双过氧钒通过激活ERK1/2信号通路调节自噬来保护脊髓损伤。
Bisperoxovanadium protects against spinal cord injury by regulating autophagy via activation of ERK1/2 signaling.
作者信息
Tang Yu-Jin, Li Kai, Yang Cheng-Liang, Huang Ke, Zhou Jing, Shi Yu, Xie Ke-Gong, Liu Jia
机构信息
Department of Orthopaedics, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangxi, China,
Academy of Orthopedics, The Third Affiliated Hospital of Southern Medical University, Guangzhou, Guangdong, China.
出版信息
Drug Des Devel Ther. 2019 Feb 1;13:513-521. doi: 10.2147/DDDT.S187878. eCollection 2019.
BACKGROUND
Spinal cord injury (SCI) is a disease of the central nervous system with few restorative treatments. Autophagy has been regarded as a promising therapeutic target for SCI. The inhibitor of phosphatase and tensin homolog deleted on chromosome ten (PTEN) bisperoxovanadium (bpV[pic]) had been claimed to provide a neuroprotective effect on SCI; but the underlying mechanism is still not fully understood.
MATERIALS AND METHODS
Acute SCI model were generated with SD Rats and were treated with control, acellular spinal cord scaffolds (ASC) obtained from normal rats, bpV(pic), and combined material of ASC and bpV(pic). We used BBB score to assess the motor function of the rats and the motor neurons were stained with Nissl staining. The expressions of the main autophagy markers LC3B, Beclin1 and P62, expressions of apoptosis makers Bax, Bcl2, PARP and Caspase 3 were detected with IF or Western Blot analysis.
RESULTS
The bpV(pic) showed significant improvement in functional recovery by activating autophagy and accompanied by decreased neuronal apoptosis; combined ASC with bpV(pic) enhanced these effects. In addition, after treatment with ERK1/2 inhibitor SCH772984, we revealed that bpV(pic) promotes autophagy and inhibits apoptosis through activating ERK1/2 signaling after SCI.
CONCLUSION
These results illustrated that the bpV(pic) protects against SCI by regulating autophagy via activation of ERK1/2 signaling.
背景
脊髓损伤（SCI）是一种中枢神经系统疾病，治疗方法有限。自噬被认为是脊髓损伤有前景的治疗靶点。十号染色体上缺失的磷酸酶及张力蛋白同源物（PTEN）的双过氧钒化合物（bpV[pic]）据称对脊髓损伤具有神经保护作用；但其潜在机制仍未完全明确。
材料与方法
用SD大鼠建立急性脊髓损伤模型，并分别给予对照组、来自正常大鼠的脱细胞脊髓支架（ASC）、bpV（pic）以及ASC与bpV（pic）的复合材料进行治疗。我们用BBB评分评估大鼠的运动功能，并用尼氏染色法对运动神经元进行染色。通过免疫荧光（IF）或蛋白质免疫印迹分析检测主要自噬标志物LC3B、Beclin1和P62的表达，以及凋亡标志物Bax、Bcl2、PARP和Caspase 3的表达。
结果
bpV（pic）通过激活自噬显著改善功能恢复，并伴有神经元凋亡减少；ASC与bpV（pic）联合使用增强了这些效果。此外，在用细胞外信号调节激酶1/2（ERK1/2）抑制剂SCH772984治疗后，我们发现bpV（pic）在脊髓损伤后通过激活ERK1/2信号通路促进自噬并抑制凋亡。
结论
这些结果表明，bpV（pic）通过激活ERK1/2信号通路调节自噬来保护脊髓免受损伤。
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