CORM-3介导小胶质细胞ICAM-1抑制放射性脑损伤炎症反应  

The effects of CORM-3 on inflammation of radiation brain injury mediated by ICAM-1 expression of microglia

作　　者：卢奎[1] 张成[2] 吴文军[1] 周敏[1] 黎捷[3] 钟健强[3] 

机构地区：[1]中山市人民医院神经内科,广东省528403 [2]中山大学附属第一医院神经科,广州510080 [3]中山大学附属博济医院神经内科,广东增城511300

出　　处：《中华临床医师杂志（电子版）》2015年第4期75-79,共5页Chinese Journal of Clinicians(Electronic Edition)

基　　金：中国博士后科学基金(2013M542232);广东省医学科研基金(B2014445);中山市医学科研基金(2013J033);中山市科技计划项目(2014A1FC059)

摘　　要：目的本研究旨在探讨水溶性一氧化碳分子释放剂(CORM-3)对放射性脑损伤炎症反应的影响及其分子机制。方法 BV2系小胶质细胞,随机分为正常对照组、单纯照射组和照射加CORM干预组,通过ELISA法测定各组照射后24 h炎症因子TNF-α、IL-1β的表达情况;采用免疫荧光法判断各组小胶质细胞激活形态,TUNEL染色比较各组共培养后原代神经元凋亡情况,并用Western blot法检测P38 MAPK通路对CORM干预放射后细胞间黏附分子1(ICAM-1)蛋白表达的影响。结果 BV2细胞放射后24 h TNF-α、IL-1β表达明显增高;CORM-3可减轻放射后小胶质细胞活化程度及炎症表达,降低了放射后TUNEL阳性细胞百分比;CORM-3抑制了放射后BV2细胞磷酸化P38及ICAM-1蛋白的表达增加,而P38抑制剂进一步下调放射后BV2细胞ICAM-1的表达。结论 CORM-3通过P38 MAPK-ICAM-1通路抑制内源性小胶质细胞活化和外源性白细胞趋化的双重调控方式改善放射后脑损伤炎症反应,进而减轻放射后炎症所致神经元损伤,这为改善鼻咽癌放疗后脑损伤的治疗提供了有潜在前景的新途径。Objective The aim of this study was to investigate the effects and molecular mechanism of CORM-3 （carbon monoxide-releasing molecule-3） on inflammation of radiation brain injury. Methods BV2 microglial cells were randomly divided into three groups： controls, irradiated, irradiated with CORM therapy. Expression level of inflammatory factors （TNF-α, IL-1β） in microglia at 24 h of post radiation was detected by ELISA. The morphology of activated microglia was observed by immunofluorescence. TUNEL staining was used to mark and compare the rate of apoptosis of co-cultured primary hippocampal neurons with each group of BV2 cells. Western blot analysis was used to detect the effect of P38 MAPK signaling on variation of ICAM-1 expression. Results The release of TNF-α and IL-1βwere markedly increased at 24 h of post-radiation. CORM-3 alleviated microglia activation of post radiation and inflammatory expression, followed by decreased percentage of positive apoptotic cells in TUNEL staining. CORM-3 inhibited the upregulated ICAM-1 and phosphorylated P38 expression in BV2 cells of post-radiation. Further more, the inhibitor of P38 down-regulated ICAM-1 expression with CORM-3 intervention. Conclusion CORM-3 has double effects that inhibits the endogenous activation of microglia and exogenous leukocyte migration to improve inflammatory injury of post-radiation by P38 〈br〉 MAPK-ICAM-1 signal pathway, followed by inflammation-induced neuronal damage, which provides a potential promising approach for radiation brain injury of NPC.

关 键 词：一氧化碳: 脑损伤 小神经胶质细胞 胞间黏附分子1 P38 

分 类 号：R730.55[医药卫生—肿瘤]