摘要
目的:研究三七皂苷R1对大鼠脑缺血再灌注损伤的保护作用及其可能机制。方法:将70只SD大鼠随机分为对照组、假手术组、模型组、三七皂苷R1低剂量组、三七皂苷R1中剂量组、三七皂苷R1高剂量组及依达拉奉组,每组10只。三七皂苷R1低、中、高剂量组大鼠分别灌胃低[25 mg/(kg·d)]、中[50 mg/(kg·d)]、高[100 mg/(kg·d)]剂量三七皂苷R1混悬液,依达拉奉组大鼠腹腔注射依达拉奉[3 mg/(kg·d)]。连续给药7 d后,除对照组和假手术组外,其余各组大鼠构建大脑中动脉阻断(MCAO)模型,再灌注24 h后取材。采用Zea Longa法进行神经功能学评价;测定脑组织含水量;采用苏木精-伊红(HE)染色评价脑组织病理变化;采用酶联免疫吸附法(ELISA)法测定脑组织IL-18和IL-1β的含量;采用蛋白质印迹法检测脑组织NLRP3、GSDMD和Caspase-1蛋白的表达。结果:模型组大鼠神经功能损伤评分、脑含水量高于假手术组(P<0.01);模型组大鼠脑组织中IL-18和IL-1β的含量及NLRP3、Caspase-1、GSDMD蛋白相对表达量高于假手术组(P<0.01)。三七皂苷R1中、高剂量组及依达拉奉组大鼠神经功能损伤评分、脑组织含水量均低于模型组(P<0.05或P<0.01);三七皂苷R1中、高剂量组及依达拉奉组大鼠脑组织中IL-18和IL-1β水平及NLRP3、Caspase-1、GSDMD蛋白相对表达量均低于模型组(P<0.05或P<0.01)。结论:三七皂苷R1对大鼠脑缺血再灌注损伤有抑制作用,其作用机制可能与抑制缺血再灌注引起的焦亡有关。
Objective:To study the protective effect of notoginsenoside R1 on cerebral ischemia-reperfusion injury in rats and its possible mechanism.Methods:Totally 70 Sprague Dawley rats were randomly divided into control group,sham operation group,model group,low dose of notoginsenoside R1 group(low dose group),medium dose of notoginsenoside R1 group(medium dose group),high dose of notoginsenoside R1 group(high dose group)and edaravone group,with 10 rats in each group.Rats in low,medium and high dose groups were given low[25 mg/(kg·d)],medium[50 mg/(kg·d)]and high[100 mg/(kg·d)]dose notoginsenoside R1 suspension by gavage,respectively.Rats in the edaravone group were given edaravone by intraperitoneal injection[3 mg/(kg·d)].After 7 days of continuous administration,except for the control group and sham operation group,the middle cerebral artery occlusion(MCAO)model was established in other groups,and samples were collected 24 hours after reperfusion.The neurofunctional evaluation was performed by the Zea-Longa method.The water content of brain tissue was determined.Hematoxylin-eosin(HE)staining was used to evaluate the pathological changes in brain tissue.Enzyme-linked immunosorbent assay(ELISA)method was used to measure the content of IL-18 and IL-1β.NLRP3,GSDMD and Caspase-1 were detected by Western blotting.Results:The model group showed significantly higher neurological scores and brain water content than sham operation group(P<0.01).The model group showed higher content of IL-18 and IL-1β,and NLRP3,Caspase-1 and GSDMD protein expression than shan operation group(P<0.01).The medium dose group,high dose group and edaravone group showed lower neurological scores and brain water content than model group(P<0.05 or P<0.01).The medium dose group,high dose group and edaravone group showed lower content of IL-18 and IL-1β,and NLRP3,Caspase-1,and GSDMD protein expression than model group(P<0.05 or P<0.01).Conclusion:Notoginsenoside R1 shows a good inhibitory effect on cerebral ischemia-reperfusion injury in rats,and its mechanism may be related to the inhibition of pyroptosis induced by ischemia-reperfusion.
作者
安喆妮
文海韬
石雅宁
覃丽
AN Zheni;WEN Haitao;SHI Yaning;QIN Li(Laboratory of Stem Cell Regulation with Chinese Medicine and Its Application,Hunan University of Chinese Medicine,Changsha Hunan 410208,China;Hunan Children Hospital,Changsha Hunan 410007,China;Science and Technology Innovation Center,Hunan University of Chinese Medicine,Changsha Hunan 410208,China;Hunan Key Laboratory of Vascular Biology and Translational Medicine,Changsha Hunan 410208,China)
出处
《中医药导报》
2024年第1期15-19,共5页
Guiding Journal of Traditional Chinese Medicine and Pharmacy
基金
国家自然科学基金面上项目(82274159)
湖南省自然科学基金科药联合基金项目(2022JJ80088)
湖南省自然科学基金青年项目(2023JJ40485)
湖南省教育厅科学研究重点项目(20A375)
湖南省教育厅优秀青年项目(22B0355)
湖南省中医药科研课题(2020108,B2023051)
中药粉体与创新药物省部共建国家重点实验室培育基地开放基金项目(21PTKF1004)
湖南中医药大学2020年度药学一流学科开放基金(2020YX08)
湖南省双一流药学学科。
关键词
脑缺血再灌注损伤
三七皂苷R1
焦亡
炎症小体
卒中
大鼠
cerebral ischemia-reperfusion injury
notoginsenoside Rl
pyroptosis
inflammasome
stroke
rat
