大豆异黄酮对大鼠缺血再灌注脑组织CaMKⅡ表达的影响
Effect of soybean isflavones on the expression of CaMKⅡ in cerebral ischemia/reperfusion tissue in rats
-
摘要: 目的：研究大豆异黄酮对缺血再灌注脑组织钙离子/钙调蛋白依赖性蛋白激酶（CaMK）Ⅱ表达的影响。方法：选取60只健康成年SD大鼠，随机分成假手术组（Sham组）、缺血再灌注组（I/R组）和大豆异黄酮预处理组（SI组），各20只。采用Longa改良线栓法制备大鼠大脑中动脉阻塞模型，缺血2 h后再灌注24 h，行神经功能缺损评分，TTC染色检测脑梗死体积，Western blotting技术检测CaMKⅡ蛋白表达。结果：I/R组神经功能缺损评分明显高于Sham组（P<0.01），与I/R组比较，SI组神经功能缺损评分明显下降（P<0.01）。I/R组梗死体积高于Sham组（P<0.01），与I/R组比较，SI组梗死体积降低（P<0.01）。I/R组缺血区CaMKⅡ蛋白表达量低于Sham组（P<0.01），与I/R组比较，SI组缺血区CaMKⅡ蛋白的表达量增加（P<0.01）。结论：大豆异黄酮可能通过上调缺血区CaMKⅡ蛋白表达，减轻缺血再灌注脑损伤。
-
关键词:
- 脑缺血 /
- 再灌注 /
- 大豆异黄酮 /
- 钙离子/钙调蛋白依赖性蛋白激酶Ⅱ
Abstract: Objective: To investigate the effects of soybean isoflavones(SI) on the expression of calcium-calmodulin dependent protein kinase(CaMK)Ⅱ in cerebral ischemia-reperfusion tissue in rats.Methods: Sixty adult healthy SD rats were randomly divided into the sham group,ischemia-reperfusion injury(I/R) group and SI pretreatment group(20 rats each group).The model of middle cerebral artery occlusion of rats were established by improving Longa's filament method.After 2 h of ischemia,the middle cerebral artery was reperfused for 24 h.The neurological behavior of the rats was scored using Longa's neurological function defect scale(NFDS),the cerebral infarction area was measured using TTC staining,and the expressions of CaMKⅡ was detected using Western blotting.Results: The score of NFDS in I/R group was obviously higher than that in sham group(P<0.01).Compared with I/R group,the NFDS score in SI group decreased significantly(P<0.01).The cerebral infarction volume in I/R group was higher than that in sham group(P<0.01).Compared with I/R group,the cerebral infarction volume in SI group decreased(P<0.01).The protein expression of CaMKⅡof the ischemic tissue in I/R group was lower than that in sham group(P<0.01).Compared with I/R group,the protein expression of CaMKⅡof the ischemic tissue increased in SI group(P<0.01).Conclusions: The mechanism of SI alleviating the cerebral ischemia/reperfusion injury maybe by upregulting the protein expression of CaMKⅡ in ischemic tissue. -
[1] KIRINO T.Delayed neuronal death in the gerbil hippocampus following ischemia[J].Brain Res,1982,239(1):57. [2] ASHPOLE NM,SONG W,BRUSTOVETSKY T,et al.Calcium/calmodulin-dependent protein kinase Ⅱ (CaMKⅡ) inhibition induces neurotoxicity via dysregulation of glutamate/calcium signaling and hyperexcitability[J].J Biol Chem,2012,287(11):8495. [3] 赵士弟,陈耀,姜丽娜,等.大豆异黄酮对脑缺血/再灌注诱导的线粒体损伤和脑细胞凋亡的影响[J].中国病理生理杂志,2014,30(12):2172. [4] QIAN Y,GUAN T,HUANG M,et al.Neuroprotection by the soy isoflavone,genistein,via inhibition of mitochondria-dependent apoptosis pathways and reactive oxygen induced-NF-κB activation in a cerebral ischemia mouse model[J].Neurochem,2012,60(8):759. [5] 赵士弟,陈耀,董银凤,等.大豆异黄酮对全脑缺血/再灌注大鼠海马神经元凋亡的影响[J].上海交通大学学报(医学版),2015,35(4):521. [6] 樊宗兵,童旭辉,李言,等.丙泊酚保护脑缺血再灌注损伤可能与缝隙连接功能的抑制相关[J].南方医科大学学报,2015,35(12):1678. [7] WANG Q,GE X,TIAN X,et al.Soy isoflavone:the multipurpose phytochemical (Review)[J].Biomed Rep,2013,1(5):697. [8] 杨锡兰,王盼,董银凤,等.大豆异黄酮和法舒地尔联合应用对大鼠脑缺血再灌注损伤的保护作用[J].蚌埠医学院学报,2016,41(6):712. [9] COULTRAP SJ,VEST RS,ASHPOLE NM,et al.CaMKⅡ in cerebral ischemia[J].Acta Pharmacol Sin,2011,32(7):861. [10] ASHPOLE NM,HUDMON A.Excitotoxic neuroprotection and vulnerability with CaMKⅡ inhibition[J].Mol Cell Neurosci,2011,46(4):720. [11] ASHPOLE NM,CHAWLA AR,MARTIN MP,et al.Loss of calcium/calmodulin-dependent protein kinase Ⅱactivity in cortical astrocytes decreases glutamate uptake and induces neurotoxic release of ATP[J].J Biol Chem,2013,288(20):14599. [12] ZHOU L,LI F,XU HB,et al.Treatment of cerebral ischemia by disrupting ischemia-induced interaction of nNOS with PSD-95[J].Nat Med,2010,16(12):1439. [13] WHEELER DG,BARRETT CF,GROTH DJ,et al.CaMKⅡ locally encodes L-type channel activity to signal to nuclear CREB in excitation transcription coupling[J].J Cell Biol,2008,183(5):849. -
点击查看大图
计量
- 文章访问数: 3983
- HTML全文浏览量: 534
- PDF下载量: 120
- 被引次数: 0
下载:
