Effect of recombinant human interleukin-1 receptor antagonist on metabotropic glutamate receptor 5 of the hippocampus following global cerebral ischemia reperfusion
- VernacularTitle:全脑缺血再灌注过程中人重组白细胞介素1受体拮抗剂对大鼠海马神经元代谢性谷氨酸受体5的影响
- Author:
Yun XIANG
;
Hao LEI
- Publication Type:Journal Article
- From:
Chinese Journal of Tissue Engineering Research
2005;9(40):158-161
- CountryChina
- Language:Chinese
-
Abstract:
BACKGROUND: Interleukin-1 receptor antagonist can relieve damage of neuron and protect nerve. Aminoglutaric acid can induce exitotoxicity through activating some kinds of aminoglutaric acid receptor, at the same time, can protect nerve through some receptors. But the relationship between them was unclear during the process of cerebral ischemia reperfusion.OBJECTIVE: To investigate the effect of neuroprotective actions of interleukin-1 receptor antagonist on hippocampal neurons, and the relationship between interleukin-1 receptor antagonist and metabotropic glutamate receptor 5 within the process of cerebral ischemic reperfusion injury.DESIGN: Completed randomized controlled study.SETTING: State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences; School of Medicine & Life, Jianghan University.MATERIALS: The experiment was performed at State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Science from May 2004 to January 2005. Totally 32 well-being pure breed male Wistar rats were selected.METHODS: Totally 32 rats were divided into four groups by method of the simple random sampling: normal group (n=8) received no surgical treatment, sham operated group (n=8) subjected to only dorsal and ventral neck midline incisions and gently dissection of the bilateral common carotid arteries free of surrounding nerve fibers without occlusion of the both vertebral arteries and common carotid arteries, saline group (n=8) suffered from the permanently occlusion of the both vertebral arteries by electrocauterization and transient (20 minutes) occlusion of bilateral common carotid arteries respectively, and received the treatment of a 2 μL normal saline injection into right lateral ventricle at the rate of 0.4 μL/minute following a needle withdrawal within 5 minutes, and experiment group (n=8) offered the same procedure of the saline group but for that the equivalent amount of rhIL-1ra took the place of normal saline into the lateral ventricle. Hematein-eosin staining was applied to observe pathological changes and immunohistochemistry (ABC) was used to survey the IR of mGluR5 varieties of the hippocampal neurons.MAIN OUTCOME MEASURES: ① Basic pathological changes of hip pocampus and cerebral cortex; ② mGluR5 immunoreactivity (IR) of hippocampus, the sensitive area to cerebral ischemia.RESULTS: Two rats were excluded from the experiment on account of their convulsion during reperfusion (one of the experiment group, another of the saline group), data of 30 rats was entered final analysis. ①Basic pathological changes of hippocampus and cerebral cortex: The Hemateineosin (H.E) staining showed that there is little pathological discrepancy between the normal group and the sham operated group, apparent neuronal degeneration such as peripheral edema around neurons, pyknosis, karyorrhexis and so onin the hippocampus and cortex of the rats of the saline group compared with those of the previous groups, and also the pronounced lower degree of neuronal degenerationin the rats of the experiment group.② mGluR5 immunoreactivity (IR) of hippocampus, the sensitive area to cerebral ischemia (absorbency): The immunohistochemistry presented that the mGluR5 immunoreactivity (IR) of CA1, CA3 areas of the normal group and sham group rats was strong positive (CA1: 0.54±0.12, 0.54±0.05; CA3:0.57±0.02, 0.58±0.08;P ＞ 0.05) Compared with of the normal group and sham group, the mGluR5 IR of the saline and the experiment groups reduced apparently (CA1: 0.30±0.03, 0.40±0.04; CA3: 0.30±0.04, 0.42±0.06;P ＜ 0.01), but the mGluR5 IR of the experiment group was quite stronger than that of the saline one (P ＜ 0.05).CONCLUSION: IL-1ra, one member of the Interleukin-1 family (system)of the cytokines, and mGluR5, one subtype of the metabotropic glutamate receptors were both involved in the pathophysiological process of the global cerebral ischemia reperfusion injury of the rat. Also, as the antagonist of the proimflammatory medium intetleukin-1 receptor, IL-1ra may show neuroprotection by affecting the mGluR5 expression of the CA1 and CA3 areas of the rat hippocampus within the process of cerebral ischemic reperfusion injury. Furthermore, here it demonstrated that besides IL-1ra, other factors might regulate the expression of mGluR5.
