金丝桃苷对大鼠颅脑损伤后炎性反应及血脑屏障通透性的影响  

Effects of hyperoside on inflammatory response and blood-brain barrier permeability in rats after traumatic brain injury

作　　者：邱会斌 姜金利[1] 李鹏强[1] 单春格 王超 QIU Hui-bin;JIANG Jin-li;LI Peng-qiang;SHAN Chun-ge;WANG Chao(Department of Neurosurgery,The First Medical Center,PLA General Hospital,Beijing 100853,China;Department of Neurosurgery,Anyang District Hospital,Puyang 455000,China)

机构地区：[1]解放军总医院第一医学中心神经外科医学部,北京100853 [2]濮阳市安阳地区医院神经外科,河南安阳455000

出　　处：《中国临床神经外科杂志》2024年第1期28-34,共7页Chinese Journal of Clinical Neurosurgery

摘　　要：目的探讨金丝桃苷对大鼠颅脑损伤(TBI)后炎性反应和血脑屏障损伤的影响及机制。方法选取60只成年SPF级SD大鼠,按随机数字表法随机分为假手术组、模型组、低剂量金丝桃苷组、高剂量金丝桃苷组、脂多糖(LPS)组、高剂量金丝桃苷+LPS组,每组10只。采用改良Feeney自由落体法建立TBI大鼠模型。低剂量、高剂量金丝桃苷组大鼠造模后以金丝桃苷药液灌胃,剂量分别为60、120 mg/kg;LPS组大鼠造模后以LPS药液灌胃,剂量为0.4 mg/kg;金丝桃苷+LPS组大鼠造模后以高剂量金丝桃苷和LPS药液灌胃;每天灌胃1次,持续14 d。灌胃结束后24 h,采用改良神经功能缺损评分(mNSS)评估神经功能,采用跳台实验检测认知功能;采用伊文思蓝(EB)定量法检测大鼠血脑屏障通透性;透射电镜观察大鼠血脑屏障结构损伤;采用ELASA检测大鼠血清及脑组织炎性介质[肿瘤坏死因子(TNF-α)、白细胞介素-17(IL-17)、诱导型一氧化氮合酶(iNOS)]水平;采用免疫印迹法检测脑组织TNF-α/NF-κB/caspase-3蛋白表达水平。结果TBI后,大鼠mNSS评分、跳台潜伏期显著降低(P<0.05),跳台犯错次数、脑组织EB含量、血清及脑组织炎性介质(TNF-α、IL-17、iNOS)水平、脑组织TNF-α和caspase-3蛋白表达及pNF-κB p65/NF-κB p65显著升高(P<0.05);LPS明显加重TBI大鼠神经损伤(P<0.05),明显增高炎性介质水平(P<0.05),明显增高TNF-α/NF-κB/caspase-3蛋白表达水平(P<0.05);金丝桃苷明显改善TBI大鼠脑损伤(P<0.05),而且呈剂量依赖性(P<0.05),高剂量金丝桃苷明显逆转LPS的作用(P<0.05)。结论金丝桃苷可通过抑制TNF-α/NF-κB/caspase-3信号通路、抑制炎性反应,进而减轻TBI大鼠血脑屏障损伤,改善大鼠神经功能。Objective To investigate the effects of hyperoside on inflammatory response and blood-brain barrier(BBB)permeability in rats after traumatic brain injury(TBI)and its underlying mechanisms.Methods Sixty adult SPF SD rats were randomly divided into sham operation group,model group,low-dose hyperoside group,high-dose hyperoside group,lipopolysaccharide(LPS)group,and high-dose hyperoside+LPS group,with 10 rats in each group.The TBI model was established by modified Feeney free fall method.Rats in the low-dose and high-dose hyperoside groups were given hyperoside solution by gavage after modeling,with doses of 60 and 120 mg/kg,respectively;rats in the LPS group were given LPS solution by gavage after modeling,with a dose of 0.4 mg/kg;rats in the hyperoside+LPS group were given hyperoside solution and LPS solution by gavage after modeling;once a day for 14 days.At 24 h after gavage,neurological function was evaluated by modified neurological severity scale(mNSS)score,cognitive function was detected by the platform jumping test,BBB permeability was detected by Evans blue(EB)quantitative method,structural damage of BBB was observed by transmission electron microscopy,levels of inflammatory mediators[tumor necrosis factor(TNF-α),interleukin-17(IL-17),inducible nitric oxide synthase(iNOS)]in serum and brain tissues were measured by ELASA,and protein expression levels of TNF-α/NF-κB/caspase-3 in brain tissue were detected by Western blotting.Results After TBI,the mNSS score and the platform latency were significantly decreased(P<0.05),while the number of platform errors,brain EB content,serum and brain inflammatory mediators,brain TNF-αand caspase-3 protein expression,and p-NF-κB p65/NF-κB p65 were significantly increased(P<0.05);LPS significantly aggravated the neurological injury of TBI rats(P<0.05),significantly increased the levels of inflammatory mediators(P<0.05),and significantly increased the TNF-α/NF-κB/caspase-3 protein expression(P<0.05);hyperoside significantly improved the brain injury of TBI rats(P<0.0

关 键 词：颅脑损伤 炎性反应 血脑屏障 金丝桃苷 TNF-α/NF-κB/caspase-3 大鼠 

分 类 号：R651.15[医药卫生—外科学]