解放军医学杂志2023，Vol.48Issue(12)：1395-1402,8.DOI:10.11855/j.issn.0577-7402.1297.2023.0524
CysLT2受体拮抗剂HAMI3379对大鼠脑缺血损伤的保护作用及其机制
Protective effect of CysLT2 receptor antagonist HAMI3379 on cerebral ischemia injury of rats and its mechanism
摘要
Abstract
Objective To explore the protective effects and mechanisms of cysteinyl leukotriene 2(CysLT2)receptor antagonist HAMI3379 on cerebral ischemia injury in rats.Methods 30 male SD rats were randomly divided into sham operation group,model group,and HAMI3379 group,with 10 rats in each group.The rats of model group were subjected to middle cerebral artery occlusion(MCAO)to construct the cerebral ischemia injury model,while HAMI3379 group received intraperitoneal injection of HAMI3379(0.2 mg/kg)before and after MCAO 30 min.The rats after cerebral ischemia injury were scored for neurological symptoms.The infarction volume of rats was observed by TTC staining,the activation marker Iba1 of microglia was detected by immunofluorescence staining,the mRNA level of M1/M2 polarized phenotype molecules of microglia was detected by Real-time PCR,the number of neurons was observed by NeuN staining,and neuronal degeneration was observed by Fluoro-Jade B staining.Western blotting assay was used to detect the expression of CysLT2 protein and nuclear factors κB-related protein Cα(PKCα),IκBα,p65 and p50 proteins in brain tissue.Results Compared with sham operation group,the neurological symptom score and cerebral infarction volume of model group were significantly increased(P<0.05).Compared with model group,the neurological symptom score and cerebral infarction volume of HAMI3379 group were significantly decreased(P<0.05).The results of immunofluorescence staining showed that the expression of microglia activation marker Iba1 was increased in brain tissue of rats after cerebral ischemia injury(P<0.05).Compared with sham operation group,mRNA expression of M1 polarized molecules(CD86,IL-1β,TNF-α)and M2 polarized molecules(CD206,TGF-β,IL-10)were significantly increased in the ischemic central brain tissue of model group(P<0.05).Compared with model group,the expression of M1 polarized molecules in HAMI3379 group was significantly downregulated(P<0.05),while the expression of M2 polarized molecules was significantly upregulated(P<0.05).Compared with sham operation group,the expressions of PKCα,IκBα,p65 and p50 in brain tissue of model group were significantly up-regulated(P<0.05);compared with model group,the expressions of PKCα,IκBα,p65,and p50 in HAMI3379 group were significantly down-regulated(P<0.05).The NeuN staining results showed that the number of neurons in the brain tissue of model group was decreased when compared with sham operation group(P<0.05),while the number of degenerated neurons was increased(P<0.05).Compared with model group,the number of neurons in HAMI3379 group was increased(P<0.05),while the number of degenerated neurons was decreased(P<0.05).Conclusions CysLT2 receptor antagonist HAMI3379 may regulate PKCα/IκBα/NF-κB signaling pathway,inhibits M1 polarization activation of microglia and promotes its transition to M2 polarization,inhibits neuronal degeneration,and plays a neuroprotective role.关键词
脑缺血损伤/CysLT2受体/小胶质细胞激活/M1/M2极化/神经元损伤Key words
cerebral ischemia injury/cysLT2 receptor/activation of microglia/M1/M2 polarization/neurons injury分类
医药卫生引用本文复制引用
李明星,应苗法,顾胜龙,赵蕊..CysLT2受体拮抗剂HAMI3379对大鼠脑缺血损伤的保护作用及其机制[J].解放军医学杂志,2023,48(12):1395-1402,8.基金项目
This work was supported by the Natural Science Foundation of Zhejiang Province(LYY20H310002,LYY21H310002,LYY19H310010),and the Traditional Chinese Medicine Science and Technology Plan Project of Zhejiang Province(2023ZF124) 浙江省自然科学基金(LYY20H310002,LYY21H310002,LYY19H310010) （LYY20H310002,LYY21H310002,LYY19H310010）
浙江省中医药科技计划项目(2023ZF124) （2023ZF124）
