槲皮素通过抑制p38丝裂原活化蛋白激酶信号通路对大鼠脊髓损伤后胶质瘢痕形成及轴突再生的影响  

Effects of quercetin on glial scar formation and axonal regeneration after acute spinal cord injury in rats and its association with p38 mitogen activated protein kinase signal pathway

作　　者：李文俊[1] 王业杨[2] 李贵涛[1] 孙鸿涛[1] 周晓忠[1] 罗俊男 

机构地区：[1]南方医科大学附属广东省第二人民医院骨科,广州510317 [2]南方医科大学第三附属医院脊柱骨科,广州510000

出　　处：《中华创伤骨科杂志》2017年第3期249-255,共7页Chinese Journal of Orthopaedic Trauma

基　　金：广东省科技计划项目（20128031800266）

摘　　要：目的探究槲皮素对大鼠脊髓损伤（SCI）后胶质瘢痕形成及轴突再生的影响及其与p38丝裂原活化蛋白激酶（MAPK）信号通路之间的联系，以便进一步阐明槲皮素对SCI的保护作用和机制。方法128只成年雌性Sprague-Dawley（SD）大鼠随机分为4组（n=32）：对照组（SCI＋saline）、干预组（SCI＋quercetin＋anisomycin）、治疗组（sct＋quercetin）和假手术组。假手术组仅行椎板切除术，其余3组参照改良Allen法制造SCI模型。损伤前、后进行BassoBeattieBresnahan（BBB）运动功能评分，术后检测各组大鼠受损脊髓组织中p38MAPK、p38MAPK磷酸化（p-p38MAPK）水平、胶质纤维酸性蛋白（GFAP）和神经丝蛋白．200（NF-200）蛋白表达情况。免疫组化检测各组脊髓的GFAP和NF-200表达情况，损伤后28d对各组脊髓进行苏木精-伊红染色。结果术后7、14、28d治疗组大鼠BBB评分高于对照组和干预组，术后3、7dSCI各组受损脊髓组织中p38MAPK磷酸化水平高于假手术组，术后3、7、14d治疗组的p38MAPK磷酸化水平低于对照组和干预组，以上差异均有统计学意义（P〈0．05）；术后28d各组的p38MAPK磷酸化水平差异均无统计学意义（P〉0．05）。SCI各组在术后各时间点NF-200和GFAP阳性细胞数均高于假手术组，治疗组的NF-200阳性细胞数较对照组和干预组增高，术后7、14、28d治疗组的GFAP阳性细胞数低于对照组与干预组，以上差异均有统计学意义（P〈0．05）。结论槲皮素抑制p38MAPK信号通路的活化后，减少了受损脊髓胶质瘢痕的形成，促进了受损脊髓组织中轴突再生，从而实现其对SCI后受损脊髓的保护作用。Objective To investigate the effects of quercetin on glial scar formation and axonal regeneration after spinal cord injury （SCI） and its association with the p38 mitogen activated protein kinase （MAPK） signal pathway. Methods 128 female Sprague-Dawley （SD） rats were randomly divided into a control group （SCI ＋ saline）, an intervention group （SCI ＋ quercetin ＋ anisomycin）, a treatment group （SCI ＋ quercetin） and a sham-operation group （ n = 32）. Basso Beattie Bresnahan （BBB） assessment and footprint analysis of the hind limb were performed on days 1, 3, 7, 14, 21 and 28 postoperation in each group. The expression levels ofp38MAPK, phosphorylation p38MAPK, glial fibrillary acidic protein （GFAP） and neurofilament protein-200 （NF-200） were detected by Western blot. The numbers of GFAP and NF-200 positive staining ceils in the injured spinal cord in each group were detected by immunohisto- chemistry. Results The BBB scores in the treatment group were significantly higher than in the inter- vention and control groups at each time point after SCI except on day 3 postoperation （ P 〈 0. 05）. The expression levels of phosphorylation p38MAPK protein in each SCI group were significantly higher than in the sham-operation group on days 3 and 7 postoperation （ P 〈 0. 05）. The expression levels of phosphorylation p38MAPK protein in the treatment group were significantly lower than in the control and intervention groups on days 3, 7 and 14 postoperation （ P 〈 O. 05）, but there was no significant difference on day 28 postoperation among all the groups （ P 〉 0.05 ）. The numbers of NF-200 and GFAP positive staining ceils were significantly greater than in the sham-operation group at each time point postoperation （ P 〈 O. 05） ; the NF-200 positive staining cells in the treatment group were significantly increased in comparison with the control and intervention groups （ P 〈 O. 05 ） ; the GFAP positive staining cells in the treatment group were signific

关 键 词：脊髓损伤 槲皮素 胶质纤维酸性蛋白 神经丝蛋白-200 p38丝裂原活化蛋 白激酶 

分 类 号：R651.2[医药卫生—外科学]