芬戈莫德对MCAO/R损伤模型大鼠的改善作用研究
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篇名: 芬戈莫德对MCAO/R损伤模型大鼠的改善作用研究
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摘要: 目的:观察芬戈莫德对大脑中动脉闭塞/再灌注(MCAO/R)损伤模型大鼠的改善作用。方法:将雄性SD大鼠随机分为假手术组、模型组和芬戈莫德低、中、高剂量组(0.5、1、2 mg/kg),每组8只。除假手术组外其余各组大鼠均采用线栓法复制MCAO/R损伤模型。各给药组大鼠均于再灌注后灌胃相应药物[再灌注1 h(第1天)灌胃1次,再灌注22.5 h(第2天)灌胃1次,随后每24 h灌胃1次,直至再灌注142.5 h(第7天)];假手术组和模型组大鼠均灌胃等容生理盐水,每天1次,连续7 d。记录各组大鼠的神经功能损伤评分、平衡木行走评分、记忆错误[工作记忆错误(WME)、参考记忆错误(RME)和总错误]次数,采用酶联免疫吸附测定法检测其血清炎症细胞因子[白细胞介素6(IL-6)、IL-8、IL-10、肿瘤坏死因子α(TNF-α)]含量,采用氯化三苯基四氮唑染色法检测其脑梗死率。结果:与假手术组比较,模型组大鼠神经缺损评分(给药第1~7天各时间点)、平衡木行走评分(给药第2、4、7天)、记忆错误次数(给药第2、4、7天)、血清炎症细胞因子含量以及脑梗死率均显著升高(P<0.05或P<0.01)。与模型组比较,芬戈莫德不同剂量组大鼠神经功能损伤评分(低剂量组给药第3~7天各时间点,中、高剂量组给药第2~7天各时间点),平衡木行走评分(低剂量组给药第7天,中剂量组给药第4、7天,高剂量组给药第2、4、7天),RME和总错误次数(低剂量组给药第4、7天,中、高剂量组给药第2、4、7天),WME次数(各剂量组给药第7天),血清L-6、IL-8、IL-10含量(各剂量组),血清TNF-α含量(中、高剂量组)以及脑梗死率(中、高剂量组)均显著降低(P<0.05或P<0.01)。结论:芬戈莫德灌胃可显著降低MCAO/R损伤模型大鼠的神经功能损伤评分和平衡木行走评分,并减少其记忆错误次数,具有一定的脑保护和记忆功能改善作用。上述作用可能与芬戈莫德下调IL-6、TNF-α等炎症细胞因子的表达有关。
ABSTRACT: OBJECTIVE: To observe improvement effects of fingolimod on middle cerebral artery occlusion/reperfusion (MCAO/R) injury model rats. METHODS: Male SD rats were randomly divided into sham operation group, model group and fingolimod low-dose, medium-dose and high-dose groups (0.5, 1, 2 mg/kg), with 8 rats in each group. Except for sham operation group, MCAO/R injury model was induced by suture-occluded method in other groups. Administration groups were given relevant medicine intragastrically after reperfusion [1 h after reperfusion (1st day), 22.5 h after reperfusion (2nd day), and then every 24 h until 142.5 h of reperfusion (7th day)]. Sham operation group and model group were given constant volume of normal saline intragastrically, once a day, for consecutive 7 d. The scores of neurological deficit and balance beam test, the times of memory error [work memory error (WME), reference memory error (RME) and total error] were recorded in each group. The contents of serum inflammatory cytokines (IL-6, IL-8, IL-10, TNF-α) were determined by ELISA, and triphenyl tetrazolium chloride staining method was used to detect the rate of cerebral infarction. RESULTS: Compared with sham operation group, neurological deficit scores (at different time points of 1st-7th day after administration), balance beam test scores (2nd, 4th, 7th day after administration), times of memory error (2nd, 4th, 7th day after administration), the contents of serum inflammatory cytokines and the rate of cerebral infarction were increased significantly in model group (P<0.05 or P<0.01). Compared with model group, neurological deficit scores (low-dose group at different time points of 3rd-7th day, medium-dose and high-dose groups at different time points of 2nd-7th day after administration), balance beam test scores (low-dose group at 7th day, medium-dose group at 4th and 7th day, high-dose group at 2nd, 4th, 7th day), RME times and total error times (low-dose group at 4th and 7th day, medium-dose group and high-dose group at 2nd, 4th, 7th day after administration), WME times (administrations groups at 7th day after administration), serum contents of IL-6, IL-8 and IL-10 (administrations groups), serum contents of TNF-α (medium-dose and high-does groups) and cerebral infarction rate (medium-dose and high-dose groups) were all decreased significantly (P<0.05 or P<0.01). CONCLUSIONS: Intragastric administration of fingolimod can significantly reduce neurological deficit score, balance beam test score and the times of memory error in MCAO/R injury model rats, and has a protective effect on cerebral tissue and memory function. These effects may be related to the down-regulation of inflammatory cytokines such as IL-6 and TNF-α by fingolimod.
期刊: 2019年第30卷第6期
作者: 李万平,何小苏,陶磊,崔雪萍,高源,胡园,黄茜,巫秀美
AUTHORS: LI Wanping,HE Xiaosu,TAO Lei,CUI Xueping,GAO Yuan,HU Yuan,HUANG Xi,WU Xiumei
关键字: 芬戈莫德;大脑中动脉闭塞/再灌注损伤;神经功能损伤评分;平衡木行走评分;记忆功能;炎症细胞因子;灌胃;大鼠
KEYWORDS: Fingomode; Middle cerebral artery occlusion/reperfusion injury; Neurological deficit score; Balance beam test score; Memory function; Inflammatory cytokines; Intragastric administration; Rats
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