红景天苷对脑缺血再灌注模型大鼠的治疗作用及其在脑组织中的动态含量研究  

Therapeutic Effect of Salidroside on Cerebral Ischemia Reperfusion Model Rats and Its Dynamic Content in Brain Tissue

作　　者：曹慧 宋玉晨 张颖[1] 郑晓宇 宋文婷[1] CAO Hui;SONG Yuchen;ZHANG Ying;ZHENG Xiaoyu;SONG Wenting(Institute of Basic Medical Sciences of Xiyuan Hospital,China Academy of Chinese Medical Sciences,Beijing Key Laboratory of Pharmacology of Chinese Materia Medica,Beijing 100091,China)

机构地区：[1]中国中医科学院西苑医院基础医学研究所,北京市中药药理重点实验室,北京100091

出　　处：《中药新药与临床药理》2022年第2期180-186,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：中央公益性科研院所基本科研业务费专项资金资助(ZZ13-YQ-007);国家自然科学基金青年项目(81603617)。

摘　　要：目的探究红景天苷在缺血再灌注大鼠脑组织及血浆中的分布规律,阐明并验证红景天苷可能的起效部位。方法建立大鼠大脑中动脉栓塞模型,分为红景天苷高、中、低剂量(10、5、2.5 mg·kg^(-1))药效实验组及红景天苷药代实验组(15 mg·kg^(-1))。药代组于缺血后15、40、120 min 3个时间点分别取血并灌注取脑,LC-MS检测脑组织及血浆中红景天苷的含量。药效实验各组于缺血24 h后取脑,氯化三苯基四氮唑(TTC)法检测脑梗死面积;ELISA法检测血浆中组织因子(TF)的表达。体外观察红景天苷对氧糖剥夺(OGD)后人脑微血管内皮细胞(HCMEC)的保护作用,CCK-8法检测细胞活力,试剂盒检测细胞上清中一氧化氮(NO)的含量。结果与正常组比较,模型组大鼠出现明显的梗死灶(P<0.01),红景天苷高、中、低剂量组可明显减少缺血后的脑梗死面积(P<0.05,P<0.01),且各剂量的红景天苷可明显减轻氧糖剥夺造成的内皮损伤(P<0.01)。与正常组比较,模型组大鼠组织因子明显升高(P<0.01);而与模型组比,红景天苷高、低剂量组组织因子表达明显降低(P<0.01)。造模后脑组织与血浆中红景天苷于15 min达到最高值,左、右脑组织中红景天苷含量无明显差异,各时间点脑/血比值均低于0.1。结论红景天苷在缺血性中风急性期脑组织中的分布有限,但红景天苷可能通过保护血液侧的内皮细胞而发挥脑保护作用。Objective To investigate the distribution pattern of salidroside in brain tissue and plasma of ischemiareperfusion rats,to clarify the active site of salidroside.Methods After rat models of middle cerebral artery occlusion were built,rats were divided into salidroside high-,medium-,and low-dose groups(10,5,and 2.5 mg·kg^(-1))and a pharmacokinetic group(15 mg·kg^(-1)).Blood was collected at 3 time points(15,40,and 120 min) after ischemia,and the brain was taken out after reperfusion in the pharmacokinetic group.The levels of salidroside in brain and plasma were detected by LC-MS.The brains of salidroside high-,medium-,and low-dose groups were removed after 24 h of ischemia,and the cerebral infarct size was detected by triphenyl tetrazolium chloride(TTC)assay.Tissue factor(TF)expression in plasma was measured by ELISA.Besides,the protective effects of salidroside on human cerebral microvascular endothelial cells(HCMEC)after oxygen glucose deprivation(OGD)in vitro were investigated,the cell viability was detected by CCK-8,and the content of NO in the cell supernatant was examined by NO assay kit.Results Compared with normal group,the rats in the model group showed obvious infarct lesion(P<0.01).The high-,middle-and low-dose salidroside groups could prominently reduce the infarct size after ischemia(P<0.05,P<0.01)and significantly attenuated OGD-induced endothelial injury(P<0.01).Tissue factor was significantly increased in the model group as compared with the normal group(P<0.01),whereas TF expression in the high-and low-dose salidroside groups was significantly decreased as compared with the model group(P<0.01).The concentration of salidroside in the brain tissue and plasma reached the highest value at 15 min,and there was no significant difference between the levels of salidroside in the right-and left-brain tissues.The brain-blood ratio was lower than 0.1 at each time point.Conclusion The results indicated that although the distribution of salidroside in the brain tissue was limited during the acute phase of is

关 键 词：红景天苷 脑缺血再灌注 药代动力学 脑分布 脑保护 人脑微血管内皮细胞(HCMEC) 大鼠 

分 类 号：R285.5[医药卫生—中药学]