大麻二酚对多重脑震荡大鼠NLRP3炎性小体表达的影响
The effects of cannabidiol on the expression of NLRP3 inflammasome following multiple cerebral concussions in rats
于春泽 1杨丽芳 2段兆达 2杨毓甲 2吴春云 2于建云 3杨力2
作者信息
- 1. 昆明医科大学基础医学院人体解剖与组织胚胎学系,昆明 650500;本溪市中心医院麻醉科,本溪 117099
- 2. 昆明医科大学基础医学院人体解剖与组织胚胎学系,昆明 650500
- 3. 昆明医科大学法医学院,昆明 650500
- 折叠
摘要
目的:探究大麻二酚(CBD)对多重脑震荡(MCC)大鼠NOD样受体热蛋白结构域相关蛋白3(NLRP3)炎性小体表达的影响.方法:制备大鼠多重脑震荡模型,分为Sham组、MCC组、溶剂组(MCC+TW)、CBD-L组(10 mg/kg)及CBD-H组(40 mg/kg).应用免疫荧光双标染色法观测脑内NLRP3与小胶质细胞的变化,并用Western Blot检测NLRP3炎性小体的表达变化.结果:免疫荧光双标染色显示,MCC后皮质区大量lec-tin 阳性小胶质细胞激活,胞体增大,小胶质细胞中NLRP3的免疫荧光强度明显升高(P＜0.05);给予CBD可下调激活的小胶质细胞内NLRP3的表达,且CBD-H组较CBD-L组效果更明显(P＜0.05).Western Blot显示,大鼠MCC后皮质、海马及基底节中NLRP3、半胱氨酸天冬氨酸蛋白酶-1(caspase-1)和凋亡相关斑点样蛋白(ASC)的表达水平显著升高(P＜0.05),且皮质区升高最明显;CBD-L组和CBD-H组中上述蛋白表达下降(P＜0.05).结论:大麻二酚可抑制多重脑震荡大鼠脑内NLRP3炎性小体表达,发挥抗炎保护作用.
Abstract
Objective:To investigate the effects of cannabidiol(CBD)on the NOD-like receptor protein 3(NLRP3)inflammasome in the brains of rats with multiple cerebral concussions(MCC).Methods:Rats were subjec-ted to the MCC model and divided into Sham,MCC,vehicle(MCC+TW),CBD-L(10 mg/kg),and CBD-H(40 mg/kg)groups.Immunofluorescence double staining was used to observe changes in NLRP3 and microglial cells in the brain,and Western Blot was performed to detect the expression changes of the NLRP3 inflammasome.Results:A sig-nificant increase in lectin-positive microglial cells of the cortex with enlarged cell bodies and elevated immunofluores-cence intensity of NLRP3 in the activated microglial cells was revealed by immunofluorescence double staining following MCC(P＜0.05).The immunofluorescence intensity of NLRP3 in the activated microglial cells was downregulated by the administration of CBD,with a more pronounced effect observed in the CBD-H group compared to the CBD-L group(P＜0.05).The expression of NLRP3,caspase-1,and apoptosis-associated speck-like protein(ASC)in the cortex,hippocampus,and basal ganglia of rats following MCC was significantly increased,as shown by Western Blot analysis(P＜0.05),and cortical areas are more elevated.The expression of these proteins in different brain regions was reduced by CBD-10 and CBD-40 intervention(P＜0.05).Conclusion:Cannabidiol can reduce the inflammatory response of multiple cerebral concussions rats through NLRP3 inflammasome and protect nerve tissue.
关键词
大麻二酚/多重脑震荡/NOD样受体热蛋白结构域相关蛋白3(NLRP3)/炎症Key words
cannabidiol(CBD)/multiple cerebral concussions(MCC)/NOD-like receptor pyrindomain-associat-ed protein 3(NLRP3)inflammasome/inflammation引用本文复制引用
基金项目
国家自然科学基金(81960223)
云南省创新团队项目(202005AE160004)
云南省昆明医科大学联合专项(202301AY070001-163)
出版年
2024
NETL
NSTL
万方数据