[1]傅思铭,吴旋,谢宗义.NDP-MSH激活黑皮质素3受体通过PKC/ERK信号通路减轻小鼠脑出血后氧化应激和神经元凋亡[J].第三军医大学学报,2020,42(16):1633-1640.
 FU Siming,WU Xuan,XIE Zongyi.NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway [J].J Third Mil Med Univ,2020,42(16):1633-1640.
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NDP-MSH激活黑皮质素3受体通过PKC/ERK信号通路减轻小鼠脑出血后氧化应激和神经元凋亡(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
42卷
期数:
2020年第16期
页码:
1633-1640
栏目:
神经科学
出版日期:
2020-08-30

文章信息/Info

Title:
NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway
 
作者:
傅思铭吴旋谢宗义
重庆医科大学附属第二医院神经外科 ;重庆医科大学基础医学院人体解剖学教研室
 
Author(s):
FU Siming WU Xuan XIE Zongyi
Department of Neurosurgery, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010; 2Department of Human Anatomy, College of Basic Medical Sciences, Chongqing Medical University, Chongqing, 400016, China
 
关键词:
脑出血氧化应激神经元凋亡NDP-MSH黑皮质素受体-3
Keywords:
intracerebral hemorrhage oxidative stress neuronal apoptosis Nle4-MSH melanocortin-3 receptor
分类号:
R743.34; R965; R977.6
文献标志码:
A
摘要:
目的探讨Nle4-D-Phe7-α-MSH(NDP-MSH)激活黑皮质素受体-3(Mc3r)在小鼠脑出血(intracerebral hemorrhage,ICH)后氧化应激和神经元凋亡中的作用。方法170只小鼠按随机数字表法分为3组:Sham组(n=22)、ICH组(n=46)、ICH+NDP-MSH组(n=102),建立小鼠ICH模型。ICH后24 h进行改良Garcia评分、Beam balance评分和脑含水量测定,双标免疫荧光检测小鼠脑血肿周围组织中Mc3r和Neun共定位,ELISA检测ICH小鼠血肿周围组织的MDA、SOD、CAT含量,Western blot检测脑组织中Mc3r、PKC、ERK1/2、Bcl-2、caspase-3的表达。结果Mc3r在术后24 h达到表达高峰,在神经元中广泛分布。NDP-MSH治疗后,改良的Garicia评分和Beam balance评分显著提高(P<0.05),同侧基底神经节和皮层中的水肿显著降低(P<0.05),ROS活性明显降低(P<0.05)。下调脑组织中Mc3r和PKC的表达后p-PKC,p-ERK1/2,Bcl-2的表达明显降低,c-caspase-3升高(P<0.05)。结论NDP-MSH激活黑皮质素-3受体通过PKC/ERK信号通路改善小鼠脑出血后的氧化应激和神经元凋亡。
 
Abstract:

ObjectiveTo investigate the inhibitory effect of Nle4-D-Phe7-α-MSH (NDP-MSH) that binds to melanocortin-3 receptor (Mc3r) on oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage (ICH). MethodsA total of 170 male mice were randomly assigned into sham-operated group (n=22), ICH model group (n=46), and ICH+NDP-MSH group (n=102). The modified Garcia score, Beam balance score, and brain water content of the mice were measured 24 h after ICH. Dual-label immunofluorescence assay was used to detect the colocalization of Mc3r and the neuronal marker NeuN, and ELISA was used to detect the contents of MDA, SOD and CAT contents in the surrounding tissues of cerebral hematoma of the mice. Western blotting was performed to detect the expression of Mc3r, PKC, ERK1/2, Bcl-2, and caspase-3 in the brain tissue of the mice. ResultsThe peak level of Mc3r expression in the brain tissue of the mice occurred 24 h after ICH with a diffuse distribution in the neurons. Treatment with NDP-MSH significantly increased the modified Garcia score and Beam balance score (P<0.05), decreased water content in the ipsilateral basal ganglia and the cortex (P<0.05), and lowered ROS activity in the brain tissue of the mice with ICH (P<0.05). Down-regulation of the expressions of Mc3r and PKC using a Mc3r siRNA and staurosporinein (a PKC inhibitor), respectively, significantly decreased the expressions of p-PKC, p-ERK1/2,   and Bcl-2 and enhanced the expression of c-caspase-3 in the brain tissue of the mice (P<0.05). ConclusionNDP-MSH, by binding with Mc3r, ameliorates oxidative stress and neuronal apoptosis in mice with ICH via the PKC/ERK signaling pathway.

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更新日期/Last Update: 2020-08-17