薯蓣皂苷对脑出血大鼠模型血脑屏障和脑水肿的影响及机制研究  

Dioscin attenuates early braininjury and brain edema in rat intracerebral hemorrhage model and its mechanisms.

作　　者：曾光 洪明 杨巨亮 ZENG Guang;HONG Ming;YANG Ju-liang(Department of Neurosurgery,Fuxin Mining General Hospital,China Resources Liaojian Group,Fuxin Liaoning 123000,China.)

机构地区：[1]华润辽健集团阜新矿总医院神经外科,辽宁阜新123000

出　　处：《临床和实验医学杂志》2021年第18期1916-1920,共5页Journal of Clinical and Experimental Medicine

基　　金：辽宁省医学科学技术研究基金(编号:20180400025)。

摘　　要：目的探讨薯蓣皂苷对脑出血大鼠模型血脑屏障和脑水肿的影响及机制。方法选取50只8~10周龄无特定病原体级成年雄性SD大鼠,体重280~320 g,根据随机数字表法分为5组,每组各10只。假手术组不建模,模型组、薯蓣皂苷低、中、高剂量组采用细菌胶原酶Ⅳ注入麻醉大鼠单侧纹状体诱导脑出血大鼠模型。薯蓣皂苷低、中、高剂量组分别于造模后0.5、12、24、36 h腹腔注射不同剂量的薯蓣皂苷(20、40、80 mg/kg),假手术组和模型组则于以上时间点注射1 mL生理盐水。检测各组大鼠的神经功能、脑含水量(BWC)和血脑屏障(BBB)通透性,采用实时定量逆转录-聚合酶链反应(RT-PCR)、免疫印迹法检测大鼠脑组织中转录因子NF-E2相关因子2(Nrf2)、炎性小体NLRP3、肿瘤坏死因子-α(TNF-α)和基质金属蛋白酶9(MMP-9)表达,酶联免疫吸附试验检测大鼠血清中超氧化物歧化酶(SOD)、丙二醛(MDA)水平,免疫荧光检测大鼠脑组织中活性氧(ROS)水平。结果与对照组大鼠相比,模型组大鼠神经功能缺损、血脑屏障通透性和脑含水量增加,脑组织中Nrf2、NLRP3、TNF-α和MMP-9表达显著增加,血清中MDA水平和脑组织中ROS水平显著增加、SOD含量降低,差异均有统计学意义(P<0.05)。不同剂量薯蓣皂苷可分别显著减轻脑出血大鼠神经功能缺损、血脑屏障破坏和脑水肿,降低脑组织中Nrf2、NLRP3、TNF-α和MMP-9表达,下调血清MDA水平和脑组织中ROS水平、上调血清SOD含量,差异均有统计学意义(P<0.05)。结论本研究表明,大鼠脑出血后腹腔注射薯蓣皂苷可减轻早期脑损伤和神经功能缺损,其机制主要通过调节ROS和NRF2/NLRP3炎症小体通路实现,且其作用效果存在一定剂量依赖。Objective To investigate the effect of dioscin on blood-brain barrier(BBB)and brain edema in rats with cerebral hemorrhage and its mechanisms.Methods Fifty 8-10 week old SPF-grade adult male SD rats,weighing 280-320 g,were divided into 5 groups by random number table,each with 10 rats.The sham operation group was not modeled.The model group and the dioscin low,medium and high dose groups were injected with bacterial collagenaseⅣinto the unilateral striatum of anesthetized to induce cerebral hemorrhage in rats.Dioscin low,medium,and high dose groups were intraperitoneally injected with different doses of dioscin(20,40,80 mg/kg)at 0.5,12,24,and 36 h after modeling,respectively.And the sham operation group and the model group were injected with 1 mL of normal saline at the above time points.The neural function,brain water content(BWC)and blood-brain barrier(BBB)permeability of rats in each group were detected.The expression of transcription factor NF-E2 related factor 2(Nrf2),inflammasome NLRP3,tumor necrosis factor-α(TNF-α)and matrix metalloproteinase 9(MMP-9)in rat brain tissue were detected and reversed by quantitatively in real time record-polymerase chain reaction(RT-PCR)and Western blotting.The levels of superoxide dismutase(SOD)and malondialdehyde(MDA)in serum of rats were detected by enzyme linked immunosorbent assay.The levels of reactive oxygen species(ROS)in rat brain were detected by immunofluorescence.Results Compared with the control group,the expression of Nrf2,NLRP3,TNF-αand MMP-9 in the brain tissue were significantly increased in the model group,and the levels of SOD and MDA in the serum were up-regulated.The ROS level in the brain tissue was significantly increased in the model group,and the differences are statistically significant(P<0.05).Different doses of dioscin significantly reduced the neurological function deficit,the destruction of blood-brain barrier and brain edema,reduced the expressions of Nrf2,NLRP3,TNF-αand MMP-9 in brain tissue,and down-regulated the levels of SOD and MDA in

关 键 词：大鼠 薯蓣皂苷 脑出血 血脑屏障 脑水肿 炎症小体 

分 类 号：R285.5[医药卫生—中药学]