[1]邱会斌,姜金利,李鹏强,等.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[J].中国临床神经外科杂志,2024,29(01):28-34.[doi:10.13798/j.issn.1009-153X.2024.01.009]
 QIU Hui-bin,JIANG Jin-li,LI Peng-qiang,et al.Effects of hyperoside on inflammatory response and blood-brain barrier permeability in rats after traumatic brain injury[J].,2024,29(01):28-34.[doi:10.13798/j.issn.1009-153X.2024.01.009]
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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()
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《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
29
期数:
2024年01期
页码:
28-34
栏目:
实验研究
出版日期:
2024-01-30

文章信息/Info

Title:
Effects of hyperoside on inflammatory response and blood-brain barrier permeability in rats after traumatic brain injury
文章编号:
1009-153X(2024)01-0028-07
作者:
邱会斌姜金利李鹏强单春格王超
100853北京,解放军总医院第一医学中心神经外科医学部(邱会斌、姜金利、李鹏强、单春格、王超);455000河南安阳,濮阳市安阳地区医院神经外科(邱会斌)
Author(s):
QIU Hui-bin12 JIANG Jin-li1 LI Peng-qiang1 SHAN Chun-ge1 WANG Chao1
1. Department of Neurosurgery, The First Medical Center, PLA General Hospital, Beijing 100853, China; 2. Department of Neurosurgery, Anyang District Hospital, Puyang 455000, China
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
Keywords:
Traumatic brain injury Inflammatory response Blood-brain barrier permeability Rats TNF-α/NF-κB/caspase-3 pathway
分类号:
R 651.1+5
DOI:
10.13798/j.issn.1009-153X.2024.01.009
文献标志码:
A
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p-NF-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。
Abstract:
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-α and 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<0.05), with a dose-dependent manner; high dose hyperoside significantly reversed the effects of LPS (P<0.05). Conclusions Hyperoside can reduce the BBB injury and improve the neurological function of TBI rats by inhibiting the TNF-α/NF-κB/caspase-3 signaling pathway and inhibiting inflammatory response.

参考文献/References:

[1] ROBINSON CP. Moderate and severe traumatic brain injury [J].Continuum (Minneap Minn), 2021, 27(5): 1278-1300.
[2] GODOY DA, RABINSTEIN AA. How to manage traumatic braininjury without invasive monitoring [J]. Curr Opin Crit Care, 2022, 28(2): 111-122.
[3] KALRA S, MALIK R, SINGH G, et al. Pathogenesis and management of traumatic brain injury (TBI): role of neuroinflammation andanti-inflammatory drugs [J]. Inflammopharmacology, 2022, 30(4):1153-1166.
[4] WITCHER KG, BRAY CE, CHUNCHAI T, et al. Traumatic braininjury causes chronic cortical inflammation and neuronal dysfunction mediated by microglia [J]. J Neurosci, 2021, 41(7): 1597-1616.
[5] WANG Y, YANG Y, NA S, et al. Melatonin attenuates early braininjury via regulating miR-181a/TNF-α/NF-κB signaling pathwayfollowing subarachnoid hemorrhage in rat [J]. Acta Medica Mediterranea, 2020, 36(6): 3377-3383.
[6] AHMAD R, KHAN A, REHMAN IU, et al. Lupeol treatment attenuates activation of glial cells and oxidative-stress-mediatedneuropathology in mouse model of traumatic brain injury [J]. Int JMol Sci, 2022, 23(11): 6086-6106.
[7] YANG ST, WANG XQ, LIAO GH. Advances in pharmacologicaleffects of hyperoside [J]. Chin J Modern Applied Pharm, 2018, 35(6): 947-951.杨诗婷,王晓倩,廖广辉. 金丝桃苷的药理作用机制研究进展[J].中国现代应用药学,2018,35(6):947-951.
[8] YU Y, CAI J. Hypericin alleviates early brain injury following subarachnoid hemorrhage through regulating Akt/GSK-3β signalingpathway in rats [J]. Zhejiang Med J, 2020, 42(19): 2030-2036.俞 越,蔡 菁. 金丝桃苷在大鼠蛛网膜下腔出血后早期脑损伤中的神经保护作用及机制研究[J]. 浙江医学,2020,42(19):2030-2036.[9] CHEN X, FAMUREWA AC, TANG J, et al. Hyperoside attenuatesneuroinflammation, cognitive impairment and oxidative stress viasuppressing TNF-α/NF-κB/caspase-3 signaling in type 2 diabetesrats [J]. Nutr Neurosci, 2022, 25(8): 1774-1784.
[10] CUI LX, JIANG WK, LU DH, et al. Clinical-grade human umbilicalcord mesenchymal stem cells affect the improvement of neurologicalfunction in rats with traumatic brain injury [J]. Chin J Tissue EnginRes, 2023, 27(6): 835-839.崔连旭,江文康,陆大鸿,等. 临床级人脐带间充质干细胞对创伤性脑损伤大鼠神经功能的改善作用[J]. 中国组织工程研究,2023,27(6):835-839.
[11] JIANG FF, CHEN ZZ, XU YW, et al. Study on mechanism of hyperoside protecting cerebral ischemia reperfusion injury in rats [J].Chin J Modern Applied Pharm, 2021, 38(12): 1448-1453.江飞飞,陈志志,徐晏雯,等. 金丝桃苷保护大鼠脑缺血再灌注损伤的机制研究[J]. 中国现代应用药学,2021,38(12):1448-1453.[12] LAI GX, ZHU GD, HE HM. Geniposide attenuates cognitive dysfunction in sleep-deprived rats by in?hibiting TLR4/NF-κB signaling pathway [J]. Chin J Pathophysiol, 2020, 36(10): 1810-1817.赖根祥,朱桂东,何慧明. 栀子苷通过抑制TLR4/NF-κB信号通路减轻睡眠剥夺大鼠认知功能障碍[J]. 中国病理生理杂志,2020,36(10):1810-1817.
[13] ZHENG MH, BAI JQ. Impacts of genistein on the spoptosis andautophagy of hippocampal neurons in epileptic rats based on LKB1/AMPK signaling pathway [J]. China Pharm, 2022, 25(11): 19041910.郑明慧,白建强. 基于LKB1/AMPK信号通路探究金雀异黄酮对癫痫大鼠海马神经元凋亡和自噬的影响[J]. 中国药师,2022,25(11):1904-1910.
[14] CORRIGAN JD. Traumatic brain injury and treatment of behavioraljealth conditions [J]. Psychiatr Serv, 2021, 72(9): 1057-1064.[15] WANG J, HOU Y, ZHANG L, et al. Estrogen attenuates traumaticbrain injury by inhibiting the activation of microglia and astrocytemediated neuroinflammatory responses [J]. Mol Neurobiol, 2021, 58(3): 1052-1061.
[16] DELAGE C, TAIB T, MAMMA C, et al. Traumatic brain injury: anage-dependent view of post-traumatic neuroinflammation and itstreatment [J]. Pharmaceutics, 2021, 13(10): 1624-1670.
[17] ZHANG T, SONG XF, DU XN, et al. Protective effects of Chinesehawthorn leaf hyperoside against high glucose-induced injury inSH-SY5Y cells [J]. Nat Prod Res Dev, 2019, 31(1): 142-146, 68.张 婷,宋小锋,杜晓娜,等. 山楂叶金丝桃苷对高糖诱导SHSY5Y细胞损伤的保护作用及机制[J]. 天然产物研究与开发,2019,31(1):142-146,68.
[18] LIU JJ, ZHANG DX, CAO JW, et al. Neuroprotective effect andmechanism of hyperoside pretreatment on mice with cerebralischemia-re?perfusion injury [J]. Shandong Med J, 2021, 61(20):15-19.刘佳佳,张栋旭,曹建文,等. 金丝桃苷预处理对脑缺血再灌注损伤小鼠的神经保护作用及机制探讨[J]. 山东医药,2021,61(20):15-19.
[19] PEROVI M, JOVI M, TODOROVI S, et al. Neuroprotective effects offood restriction in a rat model of traumatic brain injury - the role ofglucocorticoid signaling [J]. Nutr Neurosci, 2022, 25(3): 537-549.
[20] XU J, ZHAN T, ZHENG W, et al. Hydroxysafflor yellow A acutelyattenuates blood-brain barrier permeability, oxidative stress,inflammation and apoptosis in traumatic brain injury in rats1 [J].Acta Cir Bras, 2021, 35(12): e351202-e351209.

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备注/Memo

备注/Memo:
(2023-07-06收稿,2023-09-12修回) 通讯作者:姜金利,E-mail:jiangjl@163.com
更新日期/Last Update: 2024-01-30