机构地区:[1]河北省邯郸市中心医院神经外四科,056001 [2]河北省邯郸市中医院内科,056001
出 处:《国际中医中药杂志》2018年第8期727-732,共6页International Journal of Traditional Chinese Medicine
基 金:邯郸市科学技术研究与发展计划项目(1723208007ZC)
摘 要:目的 研究苦参素对脑缺血再灌注模型大鼠脑组织氧化应激和炎症反应的抑制作用,并探讨其机制。方法 将140只大鼠按随机数字表法分为假手术组,模型组,苦参素低、中、高剂量组,每组28只。除假手术组外,其余各组大鼠采用线栓法制备局灶性脑缺血再灌注模型。造模后第2天开始给药。苦参素低、中、高剂量组分别腹腔注射苦参素溶液25、50、100 mg/kg,模型组与假手术组腹腔注射等体积生理盐水。连续给药7 d。通过盲法神经功能评分评测神经功能损伤,测定脑组织含水量及脑组织梗死体积;检测脑组织氧化酶活性和丙二醛(malondialdehyde, MDA)、NO、诱导型一氧化氮合酶(inducible NOS, iNOS)及炎性细胞因子水平;采用HE染色、TUNEL法观察脑组织形态结构及神经元凋亡状况;WB法检测NF-?B蛋白表达。结果 与模型组比较,苦参素中、高剂量组大鼠神经功能评分、脑组织含水量、梗死体积、凋亡指数降低(P<0.05或P<0.01);脑组织SOD[(148.68±9.12)U/mg、(161.34±10.09)U/mg比(140.63±8.47)U/mg]、CAT[(3.90±1.32)U/mg、(4.15±1.47)U/mg比(2.73±0.89)U/mg]、GSH-Px[(11.46±2.65)U/mg、(13.59±3.27)U/mg比(9.35±2.03)U/mg]活性升高,MDA[(20.18±3.59)μmol/g、(17.46±3.21)μmol/g比(29.86±5.40)μmol/g]、iNOS[(12.64±1.83)、(11.75±1.62)比(14.17±2.06)]和NO[(23.64±2.18)、(21.27±2.03)比(27.82±2.42)]、TNF-a[(43.9±6.3)nmol/L、(37.2±5.8)nmol/L比(56.3±6.9)nmol/L]、IL-1β[(715.0±68.5)nmol/L、(683.9±70.8)nmol/L比(930.8±91.4)nmol/L]、IL-6[(168.4±22.5)nmol/L、(133.7±18.1)nmol/L比(212.5±24.7)nmol/L]含量降低(P<0.05或P<0.01);脑组织NF-?B[(0.35±0.13)、(0.24±0.08)比(0.62±0.15)]蛋白表达下调(P<0.05或P<0.01)。结论 苦参素可减轻脑缺血再灌注大鼠氧化应激损伤,抑制炎症Objective To study the effect of oxymatrine on oxidative stress and inflammatory reaction after cerebral ischemia reperfusion in rat. Methods A total of 140 SD rats were randomly divided into the sham group, model group and oxymatrine low, medium, high-dose groups (28 in each group). Beyond the sham group, the other groups were established the rat model of focal cerebral ischemic reperfusion with Zea-Longa occluded suture. The the low-, medium- and high-dose matrine groups were given 25, 50, and 100 mg/kg oxymatrine solutions injected intraperitoneally from the second day after operation for 7d. , The model group and the sham group were injected with an equal volume of saline. The neurological deficits, ratio of infarct volume, water content of the brain were evaluated; the morphological changes of brain tissue were observed by HE Staining, and the cell apoptosis were observed after TUNEL staining; the activity of antioxidant enzymes and malondialdehyde (MDA) in brain tissue were measured by biochemical analysis; the content of NO and the activity of iNOS were measured; the expression of NF-?B were determined by Western blotting. The inflammatory cytokines in brain tissue were determinated. Results Compared with the model group, the neurological function score, brain tissue water content, infarct volume and apoptotic index decreased in the rats of oxymatrine medium-, high-dose groups (P〈0.05 or P〈0.01). The activity of SOD (148.68 ± 9.12 U/mg, 161.34 ± 10.09 U/mg vs. 140.63 ± 8.47 U/mg), CAT (3.90 ± 1.32 U/mg, 4.15 ± 1.47 U/mg vs. 2.73 ± 0.89 U/mg), GSH-Px (11.46 ± 2.65 U/mg, 13.59 ± 3.27 U/mg vs. 9.35 ± 2.03 U/mg) were significantly increased (P〈0.05 or P〈0.01). The content of MDA (20.18 ± 3.59 μmol/g, 17.46 ± 3.21 μmol/g vs. 29.86 ± 5.40 μmol/g), iNOS (12.64 ± 1.83 U/mg, 11.75 ± 1.62 U/mg vs. 14.17 ± 2.06 U/mg), NO (23.64 ± 2.18 μmol/g, 21.27 ± 2.03 μmol/g vs. 27.82 ± 2.42 μmol/g), TNF-α (43.9 ± 6.3 nmol/L, 37.2 ± 5.8 nmol/L vs. 56.3
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