外源性瘦素通过上调星形胶质细胞GLT-1和GLAST的表达减轻小鼠脑缺血再灌注引起的谷氨酸兴奋毒性损伤

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中文摘要：目的探究外源性瘦素(Leptin)对小鼠局灶性脑缺血再灌注损伤的保护作用及其内在机制。方法将100只C57BL/6小鼠随机分为5组:假手术(Sham)组、脑缺血/再灌注模型组(I/R组)、瘦素低剂量组(Leptin-L组，0。5 mg/kg)、瘦素中剂量组(Leptin-M组，1 mg/kg)和瘦素高剂量组(Leptin-H组，2 mg/kg)，20只/组。采用改良线栓法复制小鼠局灶性脑缺血/再灌注模型，缺血1。5 h再灌注24 h后进行神经功能评分评估神经功能缺损程度，TTC染色测定脑梗死面积，HE染色观察皮层脑组织病理变化，退化神经元染色观察皮层神经元变性损伤程度，免疫组织化学染色测定皮层脑组织胶原酸性纤维蛋白的表达和形态变化，Western blot测定皮层脑组织胶原酸性纤维蛋白蛋白表达。在此基础上，另将45只C57BL/6小鼠随机分为Sham组、I/R组和Leptin组(1 mg/kg)，15只/组。谷氨酸检测试剂盒检测皮层脑组织谷氨酸含量，免疫组织化学染色测定皮层谷氨酸-天冬氨酸转运体(GLAST)和谷氨酸转运体1(GLT-1)表达，Western blotting测定GLAST、GLT-1蛋白表达。结果与I/R组比较，瘦素明显降低小鼠神经功能缺损评分(P<0。0001)，缩小脑梗死面积(P<0。001)，减轻皮层脑组织病理损伤程度，降低皮层神经元损伤程度(P<0。0001)，维持星形胶质细胞正常形态及降低星形胶质细胞的过度增生和表达(P<0。01)，使GLT-1、GLAST表达上调(P<0。01、P<0。05)，脑组织谷氨酸含量降低(P<0。01)。结论外源性瘦素对小鼠脑缺血再灌注损伤具有明显的神经保护作用，其机制可能与调节星形胶质细胞过度增生和上调GLT-1、GLAST的表达从而降低谷氨酸的兴奋毒性损伤有关。

外文标题：Exogenous leptin improves cerebral ischemia-reperfusion-induced glutamate excitotoxic injury in mice by up-regulating GLT-1 and GLAST expression in astrocytes

外文摘要：Objective To investigate the protective effect of exogenous leptin against focal cerebral ischemia-reperfusion(I/R)injury in mice and explore the underlying mechanism.Methods A total of 100 C57BL/6 mice were randomly divided into 5 groups,including a sham-operated group,cerebral I/R model group,and 3 leptin treatment groups with intraperitoneal injections of 0.5,1.0 or 2.0 leptin immediately after occlusion of the internal carotid artery.At 24 h after reperfusion,neurological function scores of the mice were assessed,and TTC staining was used to determine the area of cerebral infarction.The pathological changes in the cortical brain tissue of the mice were observed using HE staining,and degenerative damage of the cortical neurons were assessed with Fluoro-Jade C staining.The expression of glial fibrillary acidic protein in cortical brain tissues was detected using immunohistochemistry and Western blotting.In another 45 C57BL/6 mice with sham operation,I/R modeling,or leptin(1 mg/kg)treatment,glutamic acid in the cortical brain tissue was detected using glutamate assay,and cortical glutamate-aspartate transporter(GLAST)and glutamate transporter-1(GLT-1)protein expressions were detected using immunohistochemistry.Results Compared with the I/R model mice,the leptin-treated mice had significantly lower neurological deficit scores,smaller cerebral infarct area,milder pathologies in the cortical brain tissue,and lessened cortical neuronal damage with normal morphology and less excessive proliferation of the astrocytes.Leptin treatment significantly up-regulated the expressions of GLT-1 and GLAST and lowered the content of glutamic acid in the brain tissue of the I/R mice.Conclusion Exogenous leptin has obvious neuroprotective effect against cerebral I/R injury in mice,mediated probably by controlling excessive astrocyte proliferation and up-regulating cortical GLT-1 and GLAST expressions to reduce glutamate-mediated excitotoxic injury of the astrocytes.

外文关键词：

leptincerebral ischemia-reperfusion injuryastrocytesglutamate transporter-1glutamate-aspartate transporterexcitotoxicity

作者：

陈洁、刘晨旭、王春、李丽、陶伟婷、徐婧茹、唐红辉、黄丽

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作者单位：

蚌埠医科大学病理生理学教研室,安徽蚌埠 233000

蚌埠医科大学心脑血管疾病基础与临床重点实验室,安徽蚌埠 233000

蚌埠医科大学第二附属医院全科医学科,安徽蚌埠 233000

蚌埠医科大学临床医学院,安徽蚌埠 233000

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关键词：

瘦素脑缺血再灌注损伤星形胶质细胞 GLT-1 GLAST 兴奋性毒性

基金：

安徽省教育厅自然科学重点研究项目安徽省教育厅自然科学重点研究项目蚌埠医学院"512人才培育计划"安徽省教育厅自然科学重大研究项目安徽省研究生创新创业实践项目蚌埠医学院研究生科研创新计划项目国家级大学生创新项目

项目编号：

KJ2021A06962022AH051456by51202204KJ2021ZD00912022cxcysj169Byycx22008202210367060

出版年：

2024

DOI：

10.12122/j.issn.1673-4254.2024.06.08

南方医科大学学报

南方医科大学

南方医科大学学报

CSTPCD北大核心

影响因子：1.654

ISSN：1673-4254

年,卷(期)：2024.44(6)

参考文献量33