The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats.
The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats.
复制标题
微创血肿清除术对实验性脑出血大鼠JNK信号转导通路的影响
DOI：
10.3390/ijms17050710
复制
发表时间：
2016-05-13
影响因子：
5.6
通讯作者：
Guo Y
中科院分区：
文献类型：
--
作者：
Pei H;Jiang T;Liu G;Li Z;Luo K;An J;Li G;Guo Y
目的：探讨微创血肿抽吸术（MIHA）对脑出血（ICH）后c-Jun氨基末端激酶（JNK）信号转导通路的影响。方法：将300只成年雄性Wistar大鼠随机分为假手术组、脑出血组和MIHA组。每组60只大鼠用于本实验指标检测，其余40只大鼠用于替代达到排除标准（意外死亡或手术失败）的大鼠。脑出血组和MIHA组均采用自体动脉血70 μL脑内注射诱导脑出血，MIHA组仅在脑出血后6 h给予MIHA治疗。假手术组大鼠脑内不注射任何药物，与脑出血组大鼠相同，不进行任何处理。每组随机抽取6只大鼠，持续观察脑出血后6、24、48、72、96、120 h的Bederson评分。其余各组大鼠按处死时间分为3个亚组（24、72、120 h）。采用湿重/干重比值法测定脑含水量的变化。HE染色观察皮层神经元形态。采用免疫组化（IHC）和Western blotting（WB）方法检测血肿周围脑组织中磷酸化c-Jun氨基末端激酶（pJNK）和JNK的表达。结果如下：与脑出血组相比，MIHA组pJNK表达在各时间点均明显降低（p < 0.05），Bederson评分和BWC降低，皮质神经元损伤减轻。JNK的表达水平在不同的组中没有改变。IHC和WB获得的数据显示了高度的一致性，这为检测结果提供了一定的可靠性。结论：脑出血后JNK信号转导通路被激活，pJNK表达增加。MIHA可减轻神经细胞的组织病理损伤，减轻脑水肿和神经功能缺损，其神经保护作用可能与抑制JNK信号转导通路有关。
Objective: To explore the effect of minimally invasive hematoma aspiration (MIHA) on the c-Jun NH2-terminal kinase (JNK) signal transduction pathway after intracerebral hemorrhage (ICH). Methods: In this experiment, 300 adult male Wistar rats were randomly and averagely divided into sham-operated group, ICH group and MIHA group. In each group, 60 rats were used in the detection of indexes in this experiment, while the other 40 rats were used to replace rats which reached the exclusion criteria (accidental death or operation failure). In ICH group and MIHA group, ICH was induced by injection of 70 µL of autologous arterial blood into rat brain, while only the rats in MIHA group were treated by MIHA 6 h after ICH. Rats in sham-operated group were injected nothing into brains, and they were not treated either, like rats in ICH group. In each group, six rats were randomly selected to observe their Bederson’s scales persistently (6, 24, 48, 72, 96, 120 h after ICH). According to the time they were sacrificed, the remaining rats in each group were divided into 3 subgroups (24, 72, 120 h). The change of brain water content (BWC) was measured by the wet weight to dry weight ratio method. The morphology of neurons in cortex was observed by the hematoxylin–eosin (HE) staining. The expressions of phospho-c-Jun NH2-terminal kinase (pJNK) and JNK in peri-hematomal brain tissue were determined by the immunohistochemistry (IHC) and Western blotting (WB). Results: At all time points, compared with the ICH groups, the expression of pJNK decreased obviously in MIHA groups (p < 0.05), while their Bederson’s scales and BWC declined, and neuron injury in the cortex was relieved. The expression level of JNK was not altered at different groups. The data obtained by IHC and WB indicated a high-level of consistency, which provided a certain dependability of the test results. Conclusion: The JNK signal transduction pathway could be activated after intracerebral hemorrhage, with the expressions of pJNK increasing. MIHA could relieve the histo-pathological damage of nerve cells, reducing brain edema and neurological deficits, and these neuroprotective effects might be associated with suppression of JNK signal transduction pathway.