染料木素磺酸钠减轻慢性脑缺血大鼠神经细胞焦亡的研究  

The effects of Genistein-3'-sodium sulfonate on the cortex of rats with chronic cerebral ischemia by inhibiting pyroptosis

作　　者：邢亚康 张丽梅 王恺迪 温亚娟 黎晓 帅萍 XING Ya-kang;ZHANG Li-mei;WANG Kai-di;WEN Ya-juan;LI Xiao;SHUAI Ping(School of Basic Medicine,Gannan Medical University;Department of Pathology,The First Affiliated Hospital of Gannan Medical University;Key Laboratory of Ministry of Education for Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases,Gannan Medical University,Ganzhou,Jiangxi 341000)

机构地区：[1]赣南医科大学基础医学院 [2]赣南医科大学第一附属医院病理科 [3]赣南医科大学心脑血管疾病防治教育部重点实验室,江西赣州341000

出　　处：《赣南医学院学报》2024年第1期9-14,共6页JOURNAL OF GANNAN MEDICAL UNIVERSITY

基　　金：国家自然科学基金项目(82160688);赣州市指导性科技计划项目(GZ2021ZSF018,2022B-SF9554);赣南医学院本科生科技创新项目(202010);赣南医学院神经生物研究创新团队项目(TD2021JC06)。

摘　　要：目的:探讨染料木素磺酸钠(Genistein-3′-sodium sulfonate,GSS)对慢性脑缺血大鼠大脑皮层细胞焦亡的影响。方法:采用改良型双侧颈总动脉结扎法(Bilateral carotid artery ligation,2-VO)制备慢性脑缺血大鼠模型。将大鼠随机分为假手术组(Sham)、模型组(2-VO+Vehicle)、治疗组(2-VO+GSS)3组,应用ELISA方法检测各组大鼠血清中IL-1β的活性变化;并应用Real time-PCR和Western Blot方法检测大鼠大脑皮层组织中IL-1β、NLRP3、Caspase-1、GSDMD的mRNA及(或)蛋白表达水平。结果:与假手术组相比,模型组大鼠外周血清中IL-1β含量显著升高(P=0.0429);与模型组比较,治疗组大鼠外周血清中IL-1β含量下降,但差异无统计学意义(P=0.0733)。对各组大鼠大脑皮层组织中IL-1β的mRNA及蛋白表达水平观察发现,与假手术组比较,模型组大鼠大脑皮层IL-1β的mRNA表达水平及蛋白表达水平均升高,差异有统计学意义(P=0.0255,P<0.0001);与模型组比较,治疗组大鼠大脑皮层IL-1β的mRNA表达水平及蛋白表达水平均下降,差异有统计学意义(P=0.0200,P<0.0001)。与假手术组比较,模型组大鼠大脑皮层中NLRP3、GSDMD和Caspase-1 P20的mRNA水平(P=0.0443,P=0.0229,P<0.0001)及蛋白表达水平(P=0.0003,P=0.0007,P=0.0741)均升高;与模型组比较,治疗组脑皮层中NLRP3、GSDMD和Caspase-1 P20的mRNA水平(P=0.0012,P=0.0044,P=0.0058)及蛋白表达水平(P=0.0084,P=0.0268,P=0.0385)均降低。结论:GSS可通过抑制神经细胞焦亡减轻慢性脑缺血损伤。Objective:To investigate the effect of Genistein-3'-sodium sulfonate(GSS)on cell pyroptosis in rats with chronic cerebral ischemia.Methods:A modified bilateral common carotid artery occlusion(2-VO)method was used to establish a rat model of chronic cerebral ischemia.The rats were randomly divided into sham group(Sham),model group(2-VO+Vehicle)and treatment group(2-VO+GSS).IL-1β activity in rat serum was assessed using ELISA.The mRNA and protein expression levels of IL-1β,NLRP3,Caspase-1,and GSDMD in the cortical tissue of rats were detected by real-time PCR and Western blot.Results:Compared with the sham group,the activity of IL-1β in model group rats'serum decreased significantly(P=0.0429),compared with model group,the activity of IL-1β in treatment group rats'serum decreased,but with no significant difference(P=0.0733).The study of the mRNA or protein levels of IL-1β from the cerebral cortex showed,compared with sham group,the IL-1β mRNA and protein expression were increased(P=0.0255,P<0.0001);compared with model group,the IL-1β mRNA and protein expression in the treatment group were decreased,with statistical significance(P=0.0200,P<0.0001).Compared with sham group,the mRNA levelof NLRP3、GSDMD and Caspase-1 P20(P=0.0443,P=0.0229,P<0.0001)and protein level(P=0.0003,P=0.0007,P=0.0741)in the cerebral cortex of all rats in the model group increased.Compared with model group,the mRNA level of NLRP3、GSDMDand Caspase-1 P20(P=0.0012,P=0.0044,P=0.0058)and protein level(P=0.0084,P=0.0268,P=0.0385)in the cerebral cortex of all rats in the treatment group were decreased.Conclusion:GSS may alleviate chronic cerebral ischemic injury by inhibiting neuronal pyroptosis.

关 键 词：慢性脑缺血 染料木素磺酸钠 细胞焦亡 

分 类 号：R338[医药卫生—人体生理学]