川射干有效成分衍生物在脑缺血再灌注中的抗氧化作用研究  

Antioxidant Mechanism of Active Component Derivatives of IRIDIS TECTORI RHIZOMA in Cerebral Ischemia/Reperfusion

作　　者：曾丝丝 杜仕静 罗森[2] 汤依娜[2] 曾青山 李琳 袁崇均[2] 谭正怀 Zeng Sisi;Du Shjing;Luo Sen;Tang Yina;Zeng Qingshan;Li Lin;Yuan Chongjun;Tan Zhenghuai(School of Pharmacy,Southwest Medical University,Luzhou 646000;Sichuan Provincial Key Discipline of Chinese Medicine Pharmacology,Sichuan Provincial Key Laboratory of Quality and Innovation Research of Chinese Materia Medica,Sichuan Academy of Chinese Medicine Sciences,Chengdu 610041;School of Pharmacy,Chengdu University of Traditional Chinese Medicine,Chengdu 610075;The Fourth People's Hospital of Chengdu,Chengdu 610036;Sichuan Provincial People's Hospital Jinniu Hospital,Chengdu 610000)

机构地区：[1]西南医科大学药学院,泸州646000 [2]四川省中医药科学院,中药材品质及创新中药研究四川省重点实验室,四川省中药药理学重点学科,成都610041 [3]成都中医药大学药学院,成都610075 [4]成都市第四人民医院,成都610036 [5]成都市金牛区人民医院,成都610000

出　　处：《中药药理与临床》2022年第4期85-91,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：四川省中医药重点学科(编号:2020ZDXK01);四川省公益性科研项目(编号:A-2020N-23)。

摘　　要：目的:对射干苷元衍生物5,6,7,4′-四羟基异黄酮-5′-磺酸钠防治脑缺血再灌注作用及其机理进行初步研究,以期为其后期的开发奠定坚实的基础。方法:取雄性大鼠,随机分为假手术对照组及脑缺血再灌注组,禁食不禁水12 h后,在麻醉情况下采用线栓法阻断大脑中动脉,2 h后恢复灌流。假手术对照组进行同样手术,但不阻断大脑中动脉,术后24 h将手术成功的动物随机分为模型对照组、尼莫地平20 mg/kg组、5,6,7,4′-四羟基异黄酮-5′-磺酸钠50、100和200 mg/kg组,除假手术对照组、模型对照组和尼莫地平20 mg/kg组灌胃给予等体积溶媒或药物外,其余组分别腹腔注射相应药物,每天2次,连续7次(3.5 d)。末次给药后4 h行行为学评分,取血分离血清测定生化指标,取脑组织测定其缺血梗死面积、脑含水率,观察脑组织病理改变;同时考察了5,6,7,4′-四羟基异黄酮-5′-磺酸钠对亚硝酸钠致小鼠记忆巩固障碍模型的影响;运用1,1-二苯基-2-苦基肼自由基(DPPH)、2,2-联氮-二(3-乙基-苯并噻唑-6-磺酸)二铵盐(ABTS)自由基和羟基自由基清除试验,检测5,6,7,4′-四羟基异黄酮-5′-磺酸钠的体外抗氧化作用。结果:与假手术对照组比较,模型对照组大鼠行为学评分显著提高,脑组织含水率明显增加,梗死范围显著增加,血清超氧化物还原酶(SOD)活力明显降低,还原型谷胱甘肽(GSH)含量显著降低(P<0.05或P<0.01);与模型对照组比较,5,6,7,4′-四羟基异黄酮-5′-磺酸钠各剂量组均可显著减低脑缺血再灌注大鼠行为学评分,显著减少脑梗死范围和显著增加血清SOD活力(P<0.01),同时5,6,7,4′-四羟基异黄酮-5′-磺酸钠50、100 mg/kg组可明显降低血清丙二醛(MDA)含量,200 mg/kg组可显著降低脑含水率,改善脑组织病变程度(P<0.05或P<0.01)。与正常对照组比较,模型对照组小鼠在亚硝酸钠致小鼠记忆巩固障碍模型中可明显缩短潜伏期,增加�Objective: To conduct a preliminary study on the prevention and treatment of cerebral ischemia/reperfusion(CIR) with the tectorigenin derivative 5,6,7,4′-tetrahydroxyisoflavone-5′-sodium sulfonate and its mechanism, to lay a solid foundation for later development. Methods: Male rats were randomly divided into sham operation control group and CIR group. After 12 hours of fasting but having access to water, rat middle cerebral artery was blocked by suture method under anesthesia, and the perfusion was resumed 2 hours later. Rats in sham operation control group underwent the same operation, but the middle cerebral artery was not blocked. After 24 hours of the operation, rats with successful operation were randomly divided into the model control group, nimodipine 20 mg/kg group, and 5,6,7,4′-tetrahydroxyisoflavone-5′-sodium sulfonate 50, 100 and 200 mg/kg groups. Except for the sham operation control group, model control group and nimodipine 20 mg/kg group, which were given an equal volume of vehicle by intragastric administration, the other groups were intraperitoneally injected with corresponding drugs, twice a day for 7 consecutive times(3.5 day). Behavioral scoring was performed 4 hours after the last administration. Blood was collected to separate serum for determination of biochemical indicators, and brain tissue was taken to determine ischemic infarct size, brain water content, and brain histopathology. In addition, the effect of 5,6,7,4′-tetrahydroxyisoflavone-5′-sodium sulfonate on sodium nitrite-induced memory consolidation impairment model in mice was investigated. The scavenging experiments of DPPH, ABTS and hydroxyl free radicals were used to detect the in vitro antioxidant effect of 5,6,7,4′-tetrahydroxyisoflavone-5′-sodium sulfonate. Results: Compared with the conditions in sham operation control group, the behavior score in model control group, the water content of brain tissue, and the infarct size were increased, while the activity of serum superoxide dismutase(SOD) and the level of

关 键 词：5 6 7 4′-四羟基异黄酮-5′-磺酸钠 脑缺血再灌注 脑组织损伤 抗氧化 

分 类 号：R285[医药卫生—中药学]