二甲胺四环素在蛛网膜下腔出血中保护作用的研究被引量：3

Neuroprotection effect of minocycline on early brain injury after subarachnoid hemorrhage in rats

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摘要目的研究二甲胺四环素对蛛网膜下腔出血(SAH)后早期脑损伤的保护作用及其机制。方法血管内穿刺法建立SD大鼠SAH模型,将77只SD大鼠随机分为空白对照组(22只)、SAH+溶剂组(28只)、SAH+二甲胺四环素组(27只),术后1h予以腹腔注射二甲胺四环素(135mg/kg)或者等量溶剂,术后24h分别评估各组大鼠死亡率、SAH评分、神经功能评分和脑含水量情况,以Western blot检测Bcl-2和caspase-3蛋白表达,TUNEL染色检测神经细胞凋亡。结果SAH+溶剂组大鼠死亡率(21.4%)和SAH+二甲胺四环素组死亡率(18.5%)均明显高于空白对照组(均P<0.05),但前两组间无统计学差异(P>0 05)。SAH+二甲胺四环素组脑含水量(79.36±0.07)%低于SAH+溶剂组(80.00±0.16)%,组间比较有统计学差异(P<0.05),两组脑含水量均高于空白对照组(79.13±0 08)%,均有统计学差异(均P<0.05)。空白对照组Bcl-2蛋白表达为1.00±0.12,caspase-3蛋白表达为1.00±0.21,SAH+溶剂组Bcl-2表达为0.65±0.03,caspase-3表达为1.53±0.24,与空白对照组比较,SAH+溶剂组Bcl-2表达明显降低,caspase-3表达明显升高(均P<0.05),SAH+二甲胺四环素组Bcl-2表达为0.93±0.13,caspase-3表达为1.11±0.18,与SAH+溶剂组比较均有统计学差异(均P<0.05)。空白对照组神经细胞TUNEL阳性率(1.75±0.96)%,SAH+溶剂组TUNEL阳性率(31.50±3.70)%,与空白对照组相比,SAH+溶剂组TUNEL阳性率明显增加(P<0.05);而SAH+二甲胺四环素组TUNEL阳性率(14 25±2.50)%,明显低于SAH+溶剂组(P<0.05)。结论二甲胺四环素可明显减轻SAH后的早期脑损伤,可能与其抑制神经细胞凋亡有关。 Objective TO investigate the effect of minocycline on early brain injury （EBI） following subarachnoid hem- orrhage （SAH） in rats. Methods SAH was induced by the filament perforation model in male Sprague Dawley rats. SD rats （n=77） were randomly assigned to sham （n=22）, SAH＋vehicle （n.=28）, and SAH＋minocycline （n=27） groups. Minocycline （135 mg/kg） or equal volume of vehicle was administered 1 h after SAH induction. Mortality, neurological scores, brain edema were e- valuated 24 h after SAH. Cell apoptosis were examined by TUNEL staining, and the expression of caspase-3 and BcI-2 was as- sayed by Western blot at the same time point. Results The mortality was 21.4% in SAH＋vehicle group, 18.5% in the SAH＋minocycline group, while no death was observed in sham-operated rats; there was no significant difference in mortality be- tween SAH＋vehicle and SAH＋minocycline groups （P 〉0.05）, but the mortality in these two groups was much higher than that in sham group（P〈0.05）. The water content of brain was significantly increased in the SAH＋vehicle group （80.00±0.16）% compared with that in sham group [（79.13±0.08）%, P〈0.05]. Minocycline treatment markedly reduced brain water content （79.36±0.07）% compared with that in SAH＋vehicle group （P〈0.05）. Caspase-3 levels were markedly increased in SAH＋vehicle group （1.53±0.24） compared with sham group （1.00±0.21）. Minocycline treatment significantly reduced caspase-3 levels, compared to SAH＋vehicle group （1.11 ＋0.18, P〈0.05）. A significant decrease in Bcl-2 expression was observed in SAH＋vehicle group （0.65±0.03） compared with the sham group （1.00±0.12）. The treatment of minocycline upregulated the expression of BcI-2, compared to SAH＋vehicle group （0.93±0.13, P〈0.05）. TUNEL-positive cells were increased in the cortex of SAH＋vehicle rats, compared to sham group [（31.50±3.70）%, P〈0.05]. Minocycline treatment significantly reduced the number of TUNEL positive cells, compared to SAH＋vehicle group [（14.25±2.50）%, P〈0.05]. Conclusion Minocycline may reduce early brain injury after subarachnoid hemorrhage in rats by inhibiting cell apoptosis, which is associated with down-regulation of caspase-3 andup-regulation of Bcl-2.

作者李群李建儒曹生龙严锋陈高

机构地区温州医科大学附属第一医院神经外科浙江大学医学院附属第二医院神经外科

出处《浙江医学》 CAS 2015年第3期193-196,共4页 Zhejiang Medical Journal

关键词二甲胺四环素蛛网膜下腔出血早期脑损伤凋亡 Minocycline Subarachnoid hemorrhage Early brain injury Apoptosis

分类号 R651.1 [医药卫生—外科学]

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1Chen J, Wang L, Wu C, et aI.Melatonin-enhanced autophagy protects against neural apoptosis via a mitochondrial pathway in early brain injury following a subarachnoid hemorrhage[J].J Pineal Res,2014,56(1): 12-19.
2Garcia J H, Wagner S, Liu K F, et al.Neurological deficit and ex- tent of neuronal necrosis attributable to middle cerebral artery occlusion in rats. Statistical validation[J]. Stroke, 1995, 26(4): 627-635.
3Sugawara T, Ayer R, Jadhav V, et aI.A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model[J]. J Neurosci Methods,2008,167(2):327-334.
4Macdonald R L, Higashida R T, Keller E, et aI.Clazosentan, an endothelin receptor antagonist, in patients with aneurysmal sub- arachnoid haemorrhage undergoing surgical clipping: a ran- domised, double-blind, placebo-controlled phase 3 trial (CON- SCIOUS-2)[J].Lancet Neurol,2011,10(7):618-625.
5Pluta R M, Hansen-Schwartz J, Dreier J, et al. Cerebral va- sospasm following subarachnoid hemorrhage: time for a new world of thought[J].Neurol Res,2009,31 (2): 151 - 158.
6Hasegawa Y, Suzuki H, Sozen T, et aI.Apoptotic mechanisms for neuronal cells in early brain injury after subarachnoid hemor- rhage[J].Acta Neurochir Suppl,2011,110(Pt 1):43-48.
7Ostrowski R P, Colohan A R,Zhang J H.Molecular mechanisms of early brain injury after subarachnoid hemorrhage[J].Neurol Res, 2006,28(4):399-414.
8Garrido-Mesa N, Zarzuelo A,G 6 Ivez J. Minocycline: far beyond an antibiotic[J].Br J Pharmacol,2013,169(2):337-352.
9Fagan S C, Cronic L E,Hess D C.Minocycline development for a- cute ischemic stroke[J].Transl Stroke Res,2011,2(2):202-208.
10Vonder Haar C, Anderson G D, Elmore B E, et al.Comparison of the effect of minocycline and simvastatin on functional recovery and gene expression in a rat traumatic brain injury model[J].J Neurotrauma,2014,31(10):961-975.