摘要
目的研究阿加曲班对局灶性脑缺血模型大鼠血流动力学及血小板功能的影响,并探讨相关机制.方法将24只大脑中动脉闭塞(MCAO)模型大鼠随机分为模型组和低、高剂量实验组,每组8只;另取8只大鼠仅分离颈动脉,不插入线栓,设为假手术组.假手术组与模型组均给予腹腔注射0.9%NaCl 5 mL;低、高剂量实验组分别给予1.5和3.0 mg·kg^(-1)阿加曲班,腹腔注射.4组大鼠每天给药1次,连续给药7d.用超声诊断仪检测颅内血流动力学,用血小板功能分析仪检测血小板黏附和聚集功能,用蛋白质印迹法检测脑组织核转录因子-κB p65(NF-κB p65)、磷酸化NF-κB p65(p-NF-κB p65)和诱导型一氧化氮合酶(iNOS)蛋白的表达情况.结果低、高剂量实验组和模型组、假手术组的收缩期最大峰值血流速度分别为(49.86±7.52),(58.84±8.97),(41.23±8.20)和(69.52±10.26)cm·s^(-1),血小板黏附率分别为(15.03±1.96)%,(12.27±1.81)%,(18.86±2.10)%和(9.32±1.57)%,最大血小板聚集率分别为(52.17±6.85)%,(45.22±5.82)%,(60.30±7.93)%和(34.26±4.10)%,脑组织p-NF-κB p65/NF-κB p65分别为0.75±0.09,0.63±0.07,0.98±0.08和0.27±0.03,iNOS蛋白表达量分别为1.01±0.11,0.52±0.06,1.26±0.19和0.30±0.04.模型组的上述指标与低、高剂量实验组和假手术组比较,低剂量实验组的上述指标与高剂量实验组比较,差异均有统计学意义(均P<0.05).结论阿加曲班可改善MCAO大鼠血流动力学,抑制血小板黏附与聚集,减轻脑组织病理变化,推测其作用机制与抑制脑组织NF-κB p65磷酸化及iNOS表达有关.
Objective To study the effects of argatroban on hemodynamics and platelet function in rats with focal cerebral ischemia,and to explore the related mechanisms.Methods Twenty-four middle cerebral artery occlusion(MCAO)rats were randomly divided into model,experimental-L and experimental-H groups with 8 rats per group.Another 8 rats were only separated the carotid artery without inserting thread emboli,and set as sham-operation group.The sham-operation and model groups were given intraperitoneal injections of 0.9%NaCl 5 mL.The experimental-L,-H groups were given intraperitoneal injections of 1.5 and 3.0 mg·kg^(-1)argatroban,respectively.Four groups were administered once a day for 7 d.Intracranial hemodynamics was detected by using an ultrasonic diagnostic instrument.Plablet adhesion and aggregation function were detected by a platelet function analyzer.Western blot was used to detect brain tissue nuclear factor-κB p65(NF-κB p65),phosphorylated NF-κB p65(p-NF-κB p65)and inducible nitric oxide synthase(iNOS)protein.Results The maximum systolic peak blood flow velocity in the experimental-L,experimental-H,model and sham-operation groups were(49.86±7.52),(58.84±8.97),(41.23±8.20)and(69.52±10.26)cm·s^(-1),the platelet adhesion rates were(15.03±1.96)%,(12.27±1.81)%,(18.86±2.10)%and(9.32±1.57)%,the maximum platelet aggregation rates were(52.17±6.85)%,(45.22±5.82)%,(60.30±7.93)%and(34.26±4.10)%,the p-NF-κB p65/NF-κB p65 of brain tissue were 0.75±0.09,0.63±0.07,0.98±0.08 and 0.27±0.03,the expression levels of i NOS protein were 1.01±0.11,0.52±0.06,1.26±0.19 and 0.30±0.04.The above indexes in the model group were compared with those of experimental-L,experimental-H and model groups,the differences were statistically significant(all P<0.05).The above indexes in the experimental-L group were compared with those of experimental-H group,the differences were statistically significant(all P<0.05).Conclusion Argatroban can improve the hemodynamics of MCAO rats,inhibit platelet adhesion and aggregation,an
作者
谢仁伟
王明泉
程凌利
吴玲玲
李丽群
张清泉
洪全龙
李国前
XIE Ren-wei;WANG Ming-quan;CHENG Ling-li;WU Ling-ling;LI Li-qun;ZHANG Qing-quan;HONG Quan-long;LI Guo-qian(Department of Blood Transfusion,Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou 362000,Fujian Province,China;Department of Pharmacy,Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou 362000,Fujian Province,China;Department of Neurology,Quanzhou First Hospital Affiliated to Fujian Medical University,Quanzhou 362000,Fujian Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2022年第7期643-647,共5页
The Chinese Journal of Clinical Pharmacology
基金
福建省自然科学基金资助项目(2019J01597)。
