Mechanism of Guangxi Ilex pubescens Hook.et Arn.in radiation brain injury based on JNK/AP-1 signaling pathway
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 by γ-rays,and the mice were given intragastric administration for 14 d before and after radiation.Mor-ris 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-elec-tron 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 pro-tein 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 lev-els 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 de-creased 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 elec-tron microscope,increased lysosomes were observed,with swelling of the nucleus and cytoplasm of astrocytes;after IPH intervention,the degeneration of neurons and the morphology of glial cells in the brain tissue of mice were significantly improved.Conclusion:Guangxi IPH can improve the cognitive function of mice with radia-tion brain injury and reduce the activation of microglia and astrocytes.The mechanism may be related to reducing neuroinflammatory response and inhibiting JNK/AP-1 signaling pathway.
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