NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage <italic style="font-style: italic">via</italic> PKC/ERK signaling pathway

Siming FU; Xuan WU; Zongyi XIE

doi:10.16016/j.1000-5404.202003316

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NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway

Neurosciences | 更新时间：2026-01-09

- NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway
- Journal of Third Military Medical University Vol. 42, Issue 16, Pages: 1633-1640(2020)
- 作者机构：
  
  1.400010 重庆，重庆医科大学附属第二医院神经外科
  2.400016 重庆，重庆医科大学基础医学院人体解剖学教研室
- 作者简介：
- 基金信息：
  
  the Project of Supporting Startups for Talents Returning from Overseas of Chognqing(CX2019156);the Kuan Ren Talent Program of the Second Affiliated Hospital of Chongqing Medical University(201959)
- DOI：10.16016/j.1000-5404.202003316
  CLC： R743.34;R965;R977.6
- Received：25 March 2020，
  
  Revised：2020-04-26，
  
  Published：30 August 2020
- 稿件说明：
移动端阅览
Siming FU, Xuan WU, Zongyi XIE. NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway[J]. Journal of Third Military Medical University, 2020, 42(16): 1633-1640.
DOI：

Siming FU, Xuan WU, Zongyi XIE. NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway[J]. Journal of Third Military Medical University, 2020, 42(16): 1633-1640. DOI： 10.16016/j.1000-5404.202003316.

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(

=22)、ICH组(

=46)、ICH+NDP-MSH组(

=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(

0.05)，同侧基底神经节和皮层中的水肿显著降低(

0.05)，ROS活性明显降低(

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(

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

Objective

To 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).

Methods

A total of 170 male mice were randomly assigned into sham-operated group (

=22)

ICH model group (

=46)

and ICH+NDP-MSH group (

=102). The modified Garcia score

Beam balance score

and brain water conte

nt 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.

Results

The 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 (

0.05)

decreased water content in the ipsilateral basal ganglia and the cortex (

0.05)

and lowered ROS activity in the brain tissue of the mice with ICH (

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 (

0.05).

Conclusion

NDP-MSH

by binding with Mc3r

ameliorates oxidative stress and neuronal apoptosis in mice with ICH

via

the PKC/ERK signaling pathway.

关键词

Keywords

references

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⁰

NDP-MSH activates melanocortin-3 receptor to attenuate oxidative stress and neuronal apoptosis in mice with intracerebral hemorrhage via PKC/ERK signaling pathway

DOI：10.16016/j.1000-5404.202003316

摘要

Abstract

关键词

Keywords

references