摘要
目的:探讨广西毛冬青(IPH)对放射性脑损伤的改善作用及其机制。方法:将40只SPF级昆明小鼠随机分为对照组、IPH、放射组和放射+IPH组,每组10只。采用γ射线建立放射性脑损伤模型,放射前、后连续灌胃给药14 d。采用Morris水迷宫实验、避暗实验检测小鼠认知功能,苏木精—伊红(HE)染色和尼氏染色观察脑组织病理形态变化,电镜观察胶质细胞超微结构,酶联免疫吸附试验(ELISA)法检测血清白介素-6(IL-6)水平,免疫组织化学染色法检测脑组织c-Jun氨基末端激酶(JNK)、磷酸化(p-)JNK、激活蛋白-1(AP-1)和单核细胞趋化蛋白-1(MCP-1)蛋白表达,免疫荧光检测脑组织星型胶质细胞标记物GFAP和小胶质细胞标记物Iba-1蛋白表达,western blotting法检测脑组织JNK和p-JNK蛋白表达。结果:与对照组相比,放射组小鼠放射后7 d体重减低,血清IL-6含量升高,脑组织AP-1、MCP-1表达水平及p-JNK/JNK比值升高,小胶质细胞Iba-1和GFAP表达水平升高(均P<0.05)。与放射组比较,放射+IPH组小鼠放射后7 d体重增加,血清IL-6含量降低,脑组织AP-1、MCP-1表达水平及p-JNK/JNK比值降低,小胶质细胞Iba-1和GFAP表达水平降低(均P<0.05)。HE染色和尼氏染色显示,放射组大量细胞和神经元出现核固缩现象,小胶质细胞激活,呈圆形;电镜下可见细胞内溶酶体增多,星形胶质细胞细胞核及胞质肿胀;经IPH干预后,小鼠脑组织神经元变性情况和胶质细胞形态明显改善。结论:广西IPH能改善放射性脑损伤小鼠的认知功能,减少小胶质细胞和星形胶质细胞激活,其机制可能与减轻神经炎症反应、抑制JNK/AP-1信号通路有关。
Objective:To explore the protective effect and mechanism of Ilex pubescens Hook.et Arn.(IPH)in radiation brain injury.Methods:Forty SPF Kunming mice were randomly divided into control group,IPH group,radiation group,and radiation+IPH group,with 10 mice in each group.The model of radiation brain injury was established byγ-rays,and the mice were given intragastric administration for 14 d before and after radiation.Morris water maze test and dark avoidance test were used to detect the cognitive function of mice.Hematoxylin-eosin(HE)staining and Nissl staining were used to observe the morphological changes of brain tissue,the ultra-electron microscope was used to observe the changes of glial cells,enzyme-linked immunosorbent assay(ELISA)was used to detect the serum level of interleukin-6(IL-6),immunohistochemical method was used to detect the protein expression of c-Jun amino-terminal kinase(JNK),phosphorylated JNK(p-JNK),activator protein-1(AP-1),monocyte chemoattractant protein-1(MCP-1)in brain tissue,immunofluorescence was used to detect the protein expression of astrocyte marker GFAP and microglia marker Iba-1 in brain tissue,and western blotting was used to detect the protein expression of JNK and p-JNK in brain tissue.Results:Compared with the control group,the weight of the mice in the radiation group was reduced,and the serum IL-6 content,the expression levels of AP-1,MCP-1 and p-JNK/JNK ratio,as well as the expression levels of Iba-1 and GFAP in the microglia were increased 7 d after radiation(all P<0.05).Compared with the radiation group,the weight of the mice in the radiation+IPH group was increased,and the serum IL-6 content,the expression levels of AP-1 and MCP-1 in brain tissue and p-JNK/JNK ratio,as well as the expression levels of Iba-1 and GFAP in microglia were decreased 7 d after radiation(all P<0.05).HE staining and Nissl staining showed that a large number of cells and neurons in the radiation group appeared karyopyknosis,and microglia were activated and round;under the electron microscope,incre
作者
何改改
李婷
张馨月
孔蔺莎
阮林
王绍军
韦力
HE Gaigai;LI Ting;ZHANG Xinyue;KONG Linsha;RUAN Lin;WANG Shaojun;WEI Li(School of Basic Medical Sciences,Guangxi Medical University,Nanning 530021,China;Department of Radiotherapy,the First Affiliated Hospital of Guangxi Medical University,Nanning 530021,China;Maternity and Child Health Care of Guangxi Zhuang Autonomous Region,Nanning 530005,China)
出处
《广西医科大学学报》
CAS
2024年第1期58-66,共9页
Journal of Guangxi Medical University
基金
广西自然科学基金资助项目(No.2018JJA140600)。
关键词
广西毛冬青
放射性脑损伤
JNK/AP-1
炎症反应
认知障碍
Ilex pubescens Hook.et Arn.
radiation brain injury
c-Jun amino-terminal kinase/activator protein-1
inflammatory response
memory impairment
