淫羊藿苷调控NLRP3炎症小体抗脑缺血再灌注损伤机制  

Mechanism of icariin regulating the NLRP3 inflammasome against cerebral ischemia reperfusion

作　　者：曾奇 吴雅晨 胡茂华 笪小云 刘杨 杨欣 邓颖 刘明 ZENG Qi;WU Yachen;HU Maohua;DA Xiaoyun;LIU Yang;YANG Xin;DENG Ying;LIU Ming(Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China;Research Center of Traditional Chinese Medicine and Ethnic Drug Pharmacological Activities and Mechanism,Guizhou University of Traditional Chinese Medicine,Guiyang 550025,China)

机构地区：[1]贵州中医药大学,贵阳550025 [2]贵州中医药大学中药、民族药药理作用及作用机制研究中心,贵阳550025

出　　处：《中国实验动物学报》2024年第1期25-32,共8页Acta Laboratorium Animalis Scientia Sinica

基　　金：贵州省教育厅项目(黔教技[2022]022号);贵州省科技计划项目(黔科合基础[2019]1033号);贵州省苗医药重点实验室开放课题(黔苗医药K字[2017]019)。

摘　　要：目的探讨淫羊藿苷调控NLRP3炎症小体治疗大鼠脑缺血再灌注损伤的作用机制。方法采用线栓法制备局灶性脑缺血再灌注大鼠模型。术后24 h将大鼠随机分为假手术组,模型组,丁苯酞组(70 mg/kg),ICA低剂量组(20 mg/kg)、ICA中剂量组(40 mg/kg)、ICA高剂量组(80 mg/kg),灌胃相应药物10 mL/kg,每天给药1次,连续给药13 d。末次给药1 h后进行神经功能评分,苏木素-伊红(HE)染色法对大鼠大脑皮层进行病理学观察,免疫组化法测定大鼠大脑皮层白介素-1β(IL-1β)、白介素-18(IL-18)表达,蛋白免疫印迹法(Western Blot)测定大鼠大脑皮层NLRP3、ASC和Caspase-1蛋白表达。结果与假手术组比较,模型组大鼠神经功能评分显著增加;缺血周围区大脑皮层可见神经元不同程度坏死或胶质细胞增生,完整神经元数量显著减少;IL-1β、IL-18阳性细胞表达明显升高;NLRP3、ASC、Caspase-1蛋白表达显著增加(P<0.01,P<0.05)。经淫羊藿苷治疗后,大鼠神经功能评分明显降低;缺血周围区神经元坏死程度明显减轻,完整神经元数量显著增加;IL-1β、IL-18阳性细胞表达明显降低;NLRP3、ASC、Caspase-1蛋白表达量显著下降(P<0.01,P<0.05)。结论淫羊藿苷治疗脑缺血再灌注损伤可能与调控NLRP3炎症小体有关。Objective To investigate the mechanism of icariin regulating the NLRP3 inflammasome in the treatment of cerebral ischemia-reperfusion injury in rats.Methods A rat model of focal cerebral ischemia-reperfusion was induced using the thread embolism method.At 24 hours post-operation,the rats were randomly allocated into a sham operation group,model group,butylphthalide group(70 mg/kg),ICA-low dose(20 mg/kg),ICA-middle dose(40 mg/kg),and ICA-high dose(80 mg/kg)groups.The corresponding drugs were administered by gavage at 10 mL/kg once a day for 13 consecutive days.One hour after the last administration,neurological function was scored.The cerebral cortex was observed by hematoxylin-eosin(HE)staining.Expression of interleukin(IL)-1βand IL-18 in the cerebral cortex was determined by immunohistochemistry.Expression of NLRP3,ASC,and Caspase-1 in the cerebral cortex was determined by Western Blot.Results In contrast to the sham operation group,there was a notable increase in neural function scores within the model group.The ischemic area around the visible cerebral cortex showed neuron necrosis at various level or glial cell proliferation,and the number of intact neurons was significantly reduced.IL-1βand IL-18 positive cells were significantly increased.Expression of NLRP3,ASC,and Caspase-1 was significantly increased(P<0.01,P<0.05).After treatment with icariin,the neural function score was decreased significantly.The degree of neuronal necrosis in the peri-ischemic area was significantly reduced,and the number of intact neurons was significantly increased.IL-1βand IL-18-positive cells were decreased significantly.Expressions of NLRP3,ASC,and Caspase-1 were significantly decreased(P<0.01,P<0.05).Conclusions Treatment of cerebral ischemia-reperfusion injury by icariin may be related to regulation of the NLRP3 inflammasome.

关 键 词：淫羊藿苷 脑缺血再灌注 大脑皮层 NLRP3炎症小体 

分 类 号：Q95-33[生物学—动物学]