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甲基莲心碱抑制NLRP3炎性小体的活化缓解脑缺血再灌注大鼠脑组织损伤和免疫紊乱 被引量:9

Inhibition of NLRP3 inflammasome activation by neferine alleviates brain tissue damage and immune disorders in rats with cerebral ischemia-reperfusion
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摘要 目的探究甲基莲心碱对脑缺血再灌注大鼠脑组织损伤和免疫紊乱的影响。方法建立脑缺血再灌注大鼠模型,将大鼠随机分为5组:假手术组(sham)、大脑中动脉闭塞组(MCAO)、甲基莲心碱低剂量组(Nef 5 mg/kg)、甲基莲心碱中剂量组(Nef 10 mg/kg)和甲基莲心碱高剂量组(Nef 20 mg/kg)。进行神经功能缺损评分;干/湿法检测脑含水量;HE染色检测脑组织病理损伤程度;TUNEL染色检测神经细胞凋亡;ELISA检测脑组织和外周血中IL-6、iNOS、IL-10含量;蛋白免疫印迹检测NLRP3、ASC、Caspase-1、Caspase-3蛋白表达水平。结果与Sham组相比较,MCAO组神经功能缺损评分升高,脑含水量升高,表现出明显脑缺血再灌注病理损伤,细胞凋亡率升高,脑组织和外周血中IL-6、iNOS含量升高,NLRP3、ASC蛋白水平和cleaved Caspase-1/Caspase-1、cleaved Caspase-3/Caspase-3比值升高,差异均有统计学意义(P<0.05);与MCAO组相比较,Nef 10、20 mg/kg组神经功能缺损评分降低,脑含水量降低,病理损伤程度明显改善,细胞凋亡率降低,脑组织和外周血中IL-6、iNOS含量降低,IL-10含量升高,NLRP3、ASC蛋白水平和cleaved Caspase-1/Caspase-1、cleaved Caspase-3/Caspase-3比值降低,差异均有统计学意义(P<0.05)。结论甲基莲心碱通过抑制NLRP3炎性小体的活化缓解脑缺血再灌注大鼠脑组织损伤和免疫紊乱。 To investigate the effects of neferine on brain tissue damage and immune disorders in rats with cerebral ischemia-reperfusion,cerebral ischemia-reperfusion model was established in rats and divided into middle cerebral artery occlusion group(MCAO),low-dose Nef 5 mg/kg group,medium-dose Nef 10 mg/kg group,and highdose Nef 20 mg/kg group,with sham operation group(sham)as control.Neurological impairment was scored;moisture content of brain was measured by dry/wet method.HE staining was used to detect the pathological damage degree of brain tissue.Apoptosis of nerve cells was detected by TUNEL staining;the levels of IL-6,iNOS and IL-10 in brain tissue and peripheral blood were detected by ELISA;the protein expression levels of NLRP3,ASC,Caspase-1 and Caspase-3 were detected by Western blotting.Data showed that compared with the sham group,MCAO group demonstrated neural function defect,increased brain water content,obvious pathological injury of cerebral ischemia-reperfusion,increased cell apoptosis rate,increased levels of IL-6 and iNOS content in brain tissue and peripheral blood,as well as increased levels of NLRP3,ASC protein,cleaved Caspase-1/Caspase-1 ratio and cleaved Caspase-3/Caspase-3 ratio(P<0.05).Nef of 10 and 20 mg/kg could reverse these changes in rats of MCAO group in some degree.In conclusion,neferine could alleviate the brain tissue injury and immune disorder of cerebral ischemia-reperfusion rats by inhibiting the activation of NLRP3 inflammasome.
作者 黄华 齐书妍 张昆 杨峰 王卿 HUANG Hua;QI Shuyan;ZHANG Kun;YANG Feng;WANG Qing(Department of Basic Medicine,Nanyang Medical College,Nanyang 473000,China;Department of Thyroid and Beast Surgery,Nanyang Second People’s Hospital,Nanyang 473000,China)
出处 《免疫学杂志》 CAS CSCD 北大核心 2021年第8期704-709,共6页 Immunological Journal
关键词 脑缺血再灌注损伤 甲基莲心碱 凋亡 免疫紊乱 Cerebral ischemia reperfusion injury Methylneferine Apoptosis Immune disorder
作者简介 通信作者:黄华,E-mail:mym2968@163.com。
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