[1]杨利超 顾建军 赵中甫 闫文涛 王冠军.抑制CKLF1促进大鼠脑缺血后神经功能恢复[J].中国临床神经外科杂志,2019,(10):611-614.[doi:10.13798/j.issn.1009-153X.2019.10.011]
 YANG Li-chao,GU Jian-jun,ZHAO Zhong-fu,et al.Neuroprotective effect of cerebral tissues after ischemia through downregulation of CKLF1 and its mechanism in SD Rats[J].,2019,(10):611-614.[doi:10.13798/j.issn.1009-153X.2019.10.011]
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抑制CKLF1促进大鼠脑缺血后神经功能恢复()
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《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
期数:
2019年10期
页码:
611-614
栏目:
论著
出版日期:
2019-10-20

文章信息/Info

Title:
Neuroprotective effect of cerebral tissues after ischemia through downregulation of CKLF1 and its mechanism in SD Rats
文章编号:
1009-153X(2019)10-0611-04
作者:
杨利超 顾建军 赵中甫 闫文涛 王冠军
461000 河南,许昌市中心医院神经外科(杨利超、赵中甫、闫文涛、王冠军);450000 郑州,河南省人民医院高级卒中中心(顾建军)
Author(s):
YANG Li-chao1 GU Jian-jun2 ZHAO Zhong-fu1 YAN Wen-tao1 WANG Guan-jun1.
1. Department of Neurosurgery, Xuchang Municipal Central Hospital, Xuchang 461000; 2. Advanced Center for Stroke, He'nan Province People's Hospital, Zhengzhou 450000, China
关键词:
局灶性脑缺血趋化素样因子1神经保护细胞凋亡细胞自噬大鼠
Keywords:
Focal cerebral ischemia Chemokine-like factor 1 Neuroprotection Caspase-3 LC3-Ⅱ
分类号:
R 743.3
DOI:
10.13798/j.issn.1009-153X.2019.10.011
文献标志码:
A
摘要:
目的 探讨抑制CKLF1对局灶性脑缺血大鼠神经保护作用及其相关机制。方法 110只成年SD大鼠按数字随机表法随机分为假手术组、模型组、低剂量CKLF1抗体组、中剂量CKLF1抗体组、高剂量CKLF1抗体组,每组22只。采用大脑中动脉线栓法制作局灶性缺血再灌注模型。术后24 h,采用Longa评分法评定大鼠神经功能;采用Nissl染色检测海马神经元存活率;免疫组化染色检测海马组织LC3-Ⅱ表达;实时荧光定量PCR和蛋白免疫印迹法检测海马组织caspase-3 mRNA和蛋白表达水平。结果 抑制CKLF1显著改善大鼠神经功能Longa评分(P<0.05),显著增加海马神经元存活率(P<0.05),显著降低海马组织LC3-Ⅱ、caspase-3表达水平(P<0.05),而且均呈剂量依赖性。结论 抑制CKLF1表达对局灶性脑缺血大鼠具有神经保护作用,可能与调控自噬或凋亡有关。
Abstract:
Objective To investigate the neuroprotective effect of inhibition of chemokine-like factor 1 (CKLF1) on the cerebral tissues after focal ischemia and its mechanisms in rats. Methods One hundred and ten rats were randomly divided into 5 groups of 22 animals each, i.e. sham operation group, model group, low, middle and high dose of CKLF1 antibody-treated groups (they were experimental groups 1, 2 and 3 respectively). The focal cerebral ischemia model was made in all the groups except sham operation group.Longa scale was used to assess the neurological defect in the rats. The survival rates of hippocampus neurons were detected by Nissl staining technique. The levels of LC3-Ⅱ and caspase3 mRNA and protein expressions in the hippocampus tissues were determined respectively by immunohitochemical technique, real-time quantitative PCR and Western blotting. Results Longa scale scores were significantly higher in the model group than those in experimental group 1 (P<0.05), which were significantly higher than those in experimental group 2 (P<0.05), which were significantly higher than those in experimental group 3 (P<0.05), which were significantly higher than those in sham operation group (P<0.01). The survival rate of hippocampus neurons was significantly higher in the sham operation group than that in the experimental group 3 (P<0.05), which was significantly higher than that in the experimental group 2 (P<0.05), which was significantly higher than that in the experimental group 1 (P<0.05), which was significantly higher than that in the model group (P<0.05). The level of LC3-Ⅱ expression in the hippocampus tissues in the model group was highest and in the sham operation group was lowest. CKLF1 antibody inhibited the LC3 expression in the hippocampus tissues in a dose-dependent manner. The levels of caspase3 mRNA and protein expression in the hippocampus tissues were highest in the model group (P<0.05) and were lowest in the sham operation group (P<0.05), and CKLF1 antibody inhibited their expressions in a dose-dependent manner. Conclusions It is suggested that the inhibition of CKLF1 expression has a neuroprotective effect on the cerebral tissues in rats with focal ischemia and this neuroprotective effect may be fulfilled through the inhibition of caspase3 signaling pathway.

参考文献/References:

[1] Yao X, Derugin N, Manley GT, et al. Reduced brain edema and infarct volume in aquaporin-4 deficient mice after transient focal cerebral ischemia [J]. Neurosci Lett, 2015, 584: 368-372. [2] Lee K, Park JW, Lee B, et al. Pathologic factors of brain edema in acute ischemic stroke research [J]. Cell Mol Life Sci, 2014, 15(1): 1-5. [3] Zhen Y, Ding C, Sun J, et al. Activation of the calcium- sensing receptor promotes apoptosis by modulating the JNK/ p38 MAPK pathway in focal cerebral ischemia-reperfusion in mice [J]. Am J Transl Res, 2016, 8(2): 911-921. [4] Chen C, Chu SF, Liu DD, et al. Chemokines play complex roles in cerebral ischemia [J]. Neurochem Int, 2017, 112 (5): 146-158. [5] Yi Z, Wang Y, Xuan Z, et al. C19, a C-terminal peptide of CKLF1, decreases inflammation and proliferation of dermal capillaries in psoriasis [J]. Sci Rep, 2017, 7(1): 13890- 13901. [6] Kong LL, Hu JF, Zhang W, et al. Expression of chemokine- like factor 1 after focal cerebral ischemia in the rat [J]. Neurosci Lett, 2011, 505(1): 14-8. [7] Kong LL, Hu JF, Zhang W, et al. C19, a C-terminal peptide of chemokine-like factor 1, protects the brain against focal brain ischemia in rats[J]. Neurosci Lett, 2012, 508(1): 13- 16. [8] Longa EZ, Weinstein PR, Carlson S, et al. Reversible middle cerebrala artery occlusion without craniectomy in rats [J]. Stroke, 1989, 20(1): 84-91. [9] Kong LL, Wang ZY, Hu JF, et al. Inhibition of chemokine- like factor 1 protects against focal cerebral ischemia through the promotion of energy metabolism and anti- apoptotic effect [J]. Neurochem Int, 2014, 76(10): 91-98. [10] Springer JE, Azbill RD, Knapp PE. Activation of the caspase-3 apoptotic cascade in traumatic spinal cord injury [J]. Nat Med, 1999, 5(8): 943-946. [11] Kanbak G, Kartkaya K, Ozcelik E, et al. The neuroprotective effect of acute moderate alcohol consumption on caspase-3 mediated neuroapoptosis in traumatic brain injury: The role of lysosomal cathepsin L and nitric oxide [J]. Gene, 2013, 512(2): 492-495. [12] 冯 磊,胡丽娟,王海云,等. 外源性硫化氢对大鼠局灶性 脑缺血再灌注时神经元凋亡的影响[J]. 中华麻醉学杂 志,2016,36(1):116-119.

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备注/Memo

备注/Memo:
通讯作者:王冠军,E-mail:guanjunli6951@sina.com(2018-01-16收稿,2018-03-13修回)
更新日期/Last Update: 2019-10-20