异秦皮素治疗脑梗死大鼠的疗效观察及机制研究  

Effect and mechanism of Isofraxidin in the treatment of cerebral infarction rats

作　　者：陈历[1] 季一飞[1] 尹书斌 赵玉萍 CHEN Li;JI Yi-fei;YIN Shu-bin;ZHAO Yu-ping(Department of Neurology,the Second Clinical Medical College of North Sichuan Medical College,Nanchong Central Hospital,Nanchong 637000,Sichuan,China)

机构地区：[1]川北医学院第二临床医学院·南充市中心医院神经内科,四川南充637000

出　　处：《川北医学院学报》2022年第8期963-968,共6页Journal of North Sichuan Medical College

基　　金：国家自然科学基金(81870966);四川省南充市市校科技战略合作项目(19SXHZ0264)。

摘　　要：目的:探究异秦皮素(ISO)治疗脑梗死大鼠的疗效及机制。方法:Longa法建立大鼠大脑中动脉闭塞(MCAO)模型。32只雄性SD大鼠分为假手术组(sham组)、MCAO组、ISO 10组(10 mg/kg)和ISO 20组(20 mg/kg),每组各8只。药物组大鼠每天给予腹腔注射相应剂量的ISO;sham组、MCAO组腹腔注射相同体积的生理盐水,持续8周。评估各组神经功能后,取相应标本行TUNEL、HE和Nissl染色,测量脑组织含水量后,采用酶联免疫吸附法(ELISA)检测活性氧自由基(ROS)、血清丙二醛(MDA)和肿瘤坏死因子α(TNF-α)、白细胞介素-1β(IL-1β)、IL-6、IL-18、IL-10、超氧化物歧化酶(SOD)的含量。采用Western blotting法检测核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)和CARD结构域凋亡相关颗粒样蛋白(ASC)的表达水平。结果:两组ISO处理后均可降低脑梗死引起的神经功能评分(P<0.01)。TUNEL染色表明,两组ISO处理后均可减少脑梗死后TUNEL阳性细胞数量(P<0.01);HE和Nissl染色结果表明,两组ISO处理后均能有效减轻脑梗死后神经元损伤;ISO 20组脑梗死后脑组织水含量降低(P<0.05)。ISO 20组ROS和MDA含量均低于MCAO组(P<0.01),SOD含量高于MCAO组(P<0.01);与MCAO组比较,两组ISO处理后均可降低TNF-α、IL-6水平(P<0.01),同时IL-10水平上调(P<0.01)。两组ISO处理后均能降低NLRP3和ASC含量(P<0.01);两组ISO处理后均能降低IL-1β和IL-18水平(P<0.01)。结论:ISO可能通过调节NLRP3炎症小体来改善脑梗死后的神经炎症和氧化应激,可能是临床治疗脑梗死的潜在有效药物。Objective:To explore the effect and mechanism of Isofraxidin(ISO)in the treatment of cerebral infarction rats.Methods:The model of middle cerebral artery occlusion(MCAO)was established by Longa method.32 male Sprague Dawley rats were randomly divided into sham operation group(sham group),MCAO group,MCAO+ISO 10 group(10 mg/kg)and MCAO+ISO 20 group(20 mg/kg),with 8 rats in each group.Rats in drug group were intraperitoneally injected with the corresponding dose of ISO every day.Sham group and MCAO group were intraperitoneally injected with the same volume of normal saline.It lasts for 8 weeks.After evaluating the nerve function of each group,TUNEL,HE and Nissl staining were used to measure brain tissue water content.ELISA was used for the detection of the levels of ROS,MDA,TNF-α,IL-1β,IL-6,IL-18,SOD and IL-10.The protein expression levels of NLRP3 and ASC were detected by Western blot.Results:Both ISO groups could reduce the neurological function score caused by cerebral infarction after treatment(P<0.01).TUNEL staining showed that both groups of ISO treatment could reduce the TUNEL positive cells after cerebral infarction(P<0.01).The results of HE and Nissl staining showed that both groups of ISO treatment could effectively reduce the injury of neurons after cerebral infarction.ISO 20 group could reduce the water content of cerebral tissue after cerebral infarction(P<0.05).Compared with MCAO group,the ROS content and MDA content in ISO group were decreased(P<0.01),while SOD content was increased(P<0.01).Compared with MCAO group,the levels of TNF-α and IL-6 were decreased in both groups of ISO treatment(P<0.01),IL-10 content was increased(P<0.01).The contents of NLRP3 and ASC were decreased in both groups of ISO treatment(P<0.01).The contents of IL-1β and IL-18 were reduced in both groups of ISO treatment(P<0.01).Conclusion:ISO may ameliorate the neuroinflammation and oxidative stress of cerebral infarction via regulation of NLRP3 inflammasomes,suggesting that ISO may be an underlying and effective drug for tre

关 键 词：异秦皮素 脑梗死 神经炎症 氧化应激 NLRP3炎性小体 

分 类 号：R743.33[医药卫生—神经病学与精神病学] R285.5[医药卫生—临床医学]