| 摘要: |
| 目的探讨Humanin衍生物（[Gly14]-Humanin，HNG）预处理对大鼠局灶性脑缺血再灌注损伤后炎症反应、细胞凋亡的影响及其机制。方法将96只健康雄性SD大鼠按随机数字法分为HNG组、生理盐水组、模型组及假手术组，每组24只。采用改良的Zea-longa线栓法制备大脑中动脉缺血再灌注损伤模型，HNG组大鼠术前5d给予HNG（2滋l/kg），生理盐水组与假手术组大鼠予0.9%氯化钠溶液（2ml/kg）,均为股静脉注射，1次/d；模型组不作处理。各组大鼠在再灌注24h后进行神经功能缺损评分（NDS），采用ELISA法测定大鼠脑组织核因子-资Bp65（NF-资Bp65）及干扰素-酌（IFN-酌）水平，原位末端标记染色观察凋亡细胞数及尼氏染色检测健存神经细胞数。结果HNG组、生理盐水组、模型组及假手术组NDS分别为1.5（1.0,2.0）分、3.0（2.0,3.0）分、3.0（2.0,3.0）分和0.0（0.0,0.0）分，假手术组NDS低于另外3组，HNG组NDS低于模型组和生理盐水组（均P＜0.05）。与假手术组比较，HNG组、生理盐水组及模型组大鼠的NF-资Bp65水平[（13.48±0.85）、（22.15±0.96）、（22.62±0.64）pg/mg]，IFN-酌水平[（5.17±0.67）、（10.83±0.34）、（10.81±0.19）pg/mg]及凋亡细胞的百分率[（48.09±7.62）%、(70.19±8.33）%、（69.02±9.07）%]均较高，不重叠高倍镜视野中尼氏小体的数量[（10.57±0.51）、（5.16±0.56）和（5.65±0.98）个]较少，差异有统计学意义（P＜0.05）；HNG组大鼠的NDS、NF-资Bp65和IFN-酌水平及细胞凋亡率均低于生理盐水组及模型组，尼氏小体数多于生理盐水组及模型组，差异有统计学意义（P＜0.05）；HNG组大鼠IFN-酌与NF-资Bp65水平呈正相关（r=0.873，P＜0.01）。结论[Gly14]-Humanin可抑制脑缺血再灌注损伤过程中的局部炎症反应、减少细胞的凋亡，从而减轻临床神经功能的缺损。其机制可能与下调脑组织NF-κBp65的释放，进一步减少IFN-γ的表达有关。 |
| 关键词: [Gly14]-Humanin 脑缺血再灌注 核因子 -资B p65 干扰素 -酌 细胞凋亡 |
| DOI：10.12056/j.issn.1006-2785.2017.39.22.2016-1561 |
| 分类号: |
| 基金项目:浙江省医药卫生科技项目（201482575）；杭州市科技发展计划项目（20140633B66） |
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| Effect of [Gly14]-Humanin on inflammation and cell apoptotic in brain tissue after focal cerebral ischemia-reperfusion in rats |
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Chun’an First People's Hospital
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| Abstract: |
| Objective To investigate the effect of [Gly14]-Humanin (HNG)on inflammation and cell apoptosis in brain
tissue after focal cerebral ischemia-reperfusion injury in rats. Methods Ninety-six male Sprague-Dawley rats were randomly divided into sham-operation group, model group, normal saline (NS) group and HNG group with 24 rats in each group. The ischemia-reperfusion model was induced by middle cerebral artery occlusion(MCAO)with Zea-longa suture embolism method in rats. HNG (2滋l/kg) or normal saline (2ml/kg) were given to rats in HNG and NS group 5 days before operation (i.v. qd x5), respectively. After 4.5h of cerebral ischemia and 24h of reperfusion, neurological deficit score (NDS)was assessed, the NF-κB p65 and IFN-γ levels in cerebral tissue were measured by ELISA, neuron apoptosis was detected by Nissl and TUNEL staining; the correlation between IFN-γ and NF-κB p65 levels in cerebral tissue was analyzed. Results The median NDS values in HNG, NS, model and sham-operation groups were 1.5(1.0, 2.0), 3.0(2.0, 3.0), 3.0(2.0, 3.0)and 0.0(0.0, 0.0), respectively; the NDS
of sham-operation group was significantly lower than those of other three groups, the NDS of HNG group was significantly lower than that of model group and normal saline group (all P＜0.05). Compared with sham-operation group, the levels of NF-κB p65
in HNG group, normal saline group and model group (13.48±0.85, 22.15±0.96 and 22.62±0.64pg/mg), the levels of IFN-γ
（5.17±0.67, 10.83±0.34 and10.81±0.19pg/mg), the ratio of apoptotic neurocyte (48.09±7.62, 70.19±8.33 and 69.02±9.07) were significantly increased, and the number of neurons (10.57±0.51, 5.16±0.56 and 5.65±0.98)was significantly decreased(all P＜0.05). The NDS, NF-κB p65 and IFN-γ levels, ratio of apoptotic neurocytes in HNG group were significantly lower than those in NS group and model group; while the number of neurons was significantly higher than that in normal saline group and model group (all P＜0.05).The levels of IFN-γ was positively correlated with NF-κB p65 in HNG group (r=0.873, P＜0.01). Conclusion [Gly14]-Humanin can alleviate the inflammation and neuron apoptosis in brain tissue and mitigate the neurologic deficit after focal cerebral ischemia reperfusion injury, which may be associated with down-regulating NF-κB p65 and reducing IFN-γ levels. |
| Key words: [Gly14]-Humanin Cerebral ischemia/reperfusion NF-资B p65 IFN-酌 Cell apoptosis |
