侧脑室注射4,4'-二异硫氰基芪-2,2'-二磺酸对大鼠脑缺血再灌注损伤的影响

doi:10.3969/j.issn.1674-5817.2015.02.002

实验动物与比较医学 ›› 2015, Vol. 35 ›› Issue (2): 92-96.DOI: 10.3969/j.issn.1674-5817.2015.02.002

侧脑室注射4,4'-二异硫氰基芪-2,2'-二磺酸对大鼠脑缺血再灌注损伤的影响

袁征¹, 张璐², 武文卿¹, 袁子彦², 赵善民², 余琛琳², 林丽芳², 汤球²

1.军事医学科学院科技部条件处,北京 100036;
2.第二军医大学实验动物中心,上海 200433

收稿日期:2014-11-12 出版日期:2015-04-25 发布日期:2015-04-25
作者简介:袁征(1973-), 男, 实验师。E-mail: yuanzheng001@126.com
基金资助:
上海市科委发展基金(121409009700)

Protective Effects and Mechanisms of 4,4'-diisothiocyanostibibene-2,2'-disulfonic Acid Injected by Intarcerebroventricular against Cerebral Ischemia-reperfusion Injury Rat

YUAN Zheng¹, ZHANG Lu², WU Wen-qing¹, YUAN Zi-yan², ZHAO Shan-min², YU Chen-lin², LIN Li-fang², TANG Qiu²

1. Support Division, Department of Science and Technology, Academy of Military Medical Sciences, Beijing 10036, China;
2. Laboratory Animal Center, Second Military Medical University, Shanghai 200433, China

Received:2014-11-12 Online:2015-04-25 Published:2015-04-25

摘要/Abstract

摘要： 目的探讨侧脑室注射4,4'-二异硫氰基芪-2,2'-二磺酸(DIDS)对脑缺血再灌注(CIRI)大鼠脑组织损伤的保护作用及其机制。方法采用线栓法制备大鼠大脑中动脉栓塞(MCAO)模型,侧脑室注射法给药。脑缺血2 h再灌注24 h后用Zea-Longa标准进行神经功能评分; 红四氮唑溶液(TTC)染色法测定大鼠脑梗死面积; Western blot法测大鼠脑组织B淋巴细胞瘤-2(B-cell lymphoma-2, Bcl-2)和天冬氨酸蛋白酶-3(Caspase-3)两种蛋白的表达水平; 试剂盒测定大鼠脑组织内诱导型一氧化氮合酶(iNOS)和谷胱甘肽过氧化物酶(GSH-PX)的活性。结果 100 μmol/L DIDS侧脑室给药能改善大脑的神经功能,减少脑缺血面积,增加Bcl-2的表达,减少Caspase-3的表达,降低iNOS的活性。结论 DIDS可以通过调节凋亡相关蛋白的表达以及降低iNOS的活性对大鼠神经细胞进行保护,减轻脑缺血再灌注损伤(CIRI)造成的脑组织损伤。

关键词: 缺血再灌注损伤(CIRI), 侧脑室注射, 4, 4'-二异硫氰基芪-2, 2'-二磺酸(DIDS), B淋巴细胞瘤(Bcl-2), 天冬氨酸蛋白酶-3(Caspase-3), 诱导型一氧化氮合酶(iNOS), 谷胱甘肽过氧化物酶(GSH-PX)

Abstract: Objective To explore the protective effects and mechanisms of 4,4'-diisothiocyanostibibene-2,2'-disulfonic acid (DIDS) injected by intarcerebroventricular against cerebral ischemia-reperfusion injury (CIRI) in middle cerebral artery occlusive (MCAO) rats. Methods Focal cerebral ischemia in rats was produced by 2 h occlusion of the middle cerebral artery and 24 h reperfusion. DIDS and normal saline (NS) was injected by intarcerebroventricular. The neurologic deficit scores were investigated according to Zea-Longa's Standard. The infarct areas were assessed with software Imagepro Plus 6.0 after TTC staining. The levels of Bcl-2 and Caspase-3 in central neutral system were assessed by western blot. And the activities of inducible nitric oxide synthase (iNOS) as well as glutathione peroxidase (GSH-PX) were determined by specific kit. Results DIDS (100 μmol/L) could decrease the neurologic deficit score, reduced the infarct areas of the brain in CIRI rats, enhance the expression of Bcl-2, depresse the expression of Caspase-3, and decrease the activity of iNOS. Conclusion DIDS has a protective effect on CIRI of rat and this effect is related to enhancing the expression of Bcl-2 and diminishing Caspase-3 expression, decreasing the activity of iNOS.

Key words: Cerebral ischemia-reperfusion injury (CIRI), Intracerebroventricular injection, DIDS, Bcl-2, Caspase-3, Inducible nitric oxide (iNOS) synthase, Glutathione peroxidase (GSH-PX)

中图分类号:

Q95-33

袁征, 张璐, 武文卿, 袁子彦, 赵善民, 余琛琳, 林丽芳, 汤球. 侧脑室注射4,4'-二异硫氰基芪-2,2'-二磺酸对大鼠脑缺血再灌注损伤的影响[J]. 实验动物与比较医学, 2015, 35(2): 92-96.

YUAN Zheng, ZHANG Lu, WU Wen-qing, YUAN Zi-yan, ZHAO Shan-min, YU Chen-lin, LIN Li-fang, TANG Qiu. Protective Effects and Mechanisms of 4,4'-diisothiocyanostibibene-2,2'-disulfonic Acid Injected by Intarcerebroventricular against Cerebral Ischemia-reperfusion Injury Rat[J]. Laboratory Animal and Comparative Medicine, 2015, 35(2): 92-96.

参考文献

[1] Nakka VP, Gusain A, Mehta SL, et al.Molecular mechanisms of apoptosis in cerebral ischemia: multiple neuroprotective opportunities[J]. Mol Neurobiol, 2008, 37(1):7-38.
[2] 原相丽, 刘珂, 毛兴爱. 促红细胞生成素对大鼠脑缺血再灌注神经元凋亡、 bcl-2和bax表达的影响[J]. 新乡医学院学报, 2007, 20(1):44-46.
[3] 师堂旺, 王晓明, 张卫卫, 等. 4,4'-二异硫氰基芪-2,2'-二磺酸对大鼠缺血再灌注损伤的影响及机制[J]. 中华老年心脑血管病杂志, 2009, 11(12):965-967.
[4] Longa EZ, Weinstein PR, Carlson S, et al.Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1):84-91.
[5] 赵勇, 张璐, 蔡丽萍, 等. 小鼠侧脑室埋管给药方法的优化[J]. 实验动物与比较医学, 2014, 34(2):153-156.
[6] George P, Charles W.大鼠脑立体定位图谱[M]. 诸葛启钏(主译). 北京: 人民卫生出版社, 2005:6.
[7] Jassem W, Fuggle SV, Rela M, et al.The role of mitochondria in ischemia/reperfusion injury[J]. Transplantation, 2002, 73(4):493-499.
[8] Szabo I, Zoratti M, Gulbins E.Contribution of voltage-gated potassium channels to the regulation of apoptosis[J]. FEBS Lett, 2010, 584(10):2049-2056.
[9] Lang F, Lang KS, Wieder T, et al.Cation channels,cell volume and the death of an erythrocyte[J]. Pflugers Arch, 2003, 447(2):121-125.
[10] Liu Y, Wang B, Zhang WW, et al.Modulation of staurosporine-activated volume-sensitive outwardly rectifying Cl- channel by PI3K/Akt in cardiomyocytes[J]. Curr Pharm Des, 2013, 19(27):4859-4864.
[11] Liu AH, Cao YN, Liu HT, et al.DIDS attenuates staurosporine-induced cardiomyocyte apoptosis by PI3K/Akt signaling pathway: activation of eNOS/NO and inhibition of Bax translocation[J]. Cell Physiol Biochem, 2008, 22(1-4):177-186.
[12] Blarre T, Bertrand HO, Acher FC, et al.Molecular determinants of agonist selectivity in glutamate-gated chloride channels which likely explain the agonist selectivity of the vertebrate glycine and GABAA-〉 receptors[J]. PLoS One, 2014, 9(9):e108458.
[13] Kaila K, Price TJ, Payne JA, et al.Cation-chloride cotransporters in neuronal development, plasticity and disease[J]. Nat Rev Neurosci, 2014, 15(10):637-654.
[14] Szabo C. Multiple pathways of peroxynitrite cytotoxicity[J]. Toxicol Lett, 2003, 140-141:105-112.
[15] Virag L, Szabo E, Gergely P, et al. Peroxynitrite-induced cytotoxicity: mechanism and opportunities for intervention[J]. Toxicol Lett, 2003, 140-141:113-124.
[16] Stanyer L, Jorgensen W, Hori O, et al.Inactivation of brain mitochondrial Lon protease by peroxynitrite precedes electron transport chain dysfunction[J]. Neurochem Int, 2008, 53(3-4):95-101.
[17] 胡国恒, 祝美珍. 活血化瘀法防治脑缺血损伤的理论探讨[J]. 中华中医药杂志, 2008, 23(6):513-515.

侧脑室注射4,4'-二异硫氰基芪-2,2'-二磺酸对大鼠脑缺血再灌注损伤的影响

Protective Effects and Mechanisms of 4,4'-diisothiocyanostibibene-2,2'-disulfonic Acid Injected by Intarcerebroventricular against Cerebral Ischemia-reperfusion Injury Rat

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	杨平, 崔立, 俞诚, 温智越. 贝伐珠单抗注射液对食蟹猴皮肤伤口愈合的影响[J]. 实验动物与比较医学, 2023, 43(1): 21-29.
[2]	王怡如, 蒋笑影, 董若曦, 潘一滨, 韩向晖, 曹永清. 三硝基苯磺酸诱导急性肠纤维化大鼠模型的改良方法[J]. 实验动物与比较医学, 2022, 42(4): 284-293.
[3]	卢晓, 张林, 季辉, 江善祥. 新型钠磷转运蛋白抑制剂DZ1462在5/6肾切除高磷血症模型大鼠中的药效研究[J]. 实验动物与比较医学, 2022, 42(3): 187-193.
[4]	高诚. 《实验动物与比较医学》创刊40年重点文献回顾（续）[J]. 实验动物与比较医学, 2021, 41(2): 169-173.
[5]	高诚. 《实验动物与比较医学》创刊40年重要文献回顾[J]. 实验动物与比较医学, 2021, 41(1): 17-26.
[6]	李萍, 李艺杰, 薛玲, 宋春红. 芍药苷对Bayk8644诱导大鼠抑郁焦虑样行为的改善作用及机制研究[J]. 实验动物与比较医学, 2020, 40(6): 489-495.
[7]	周亚妮, 刘丹. 抗C5aR抗体联合大蒜素对诱发性炎性肠病大鼠的治疗作用[J]. 实验动物与比较医学, 2020, 40(4): 328-.
[8]	李磊, 李向利, 胡惠敏. 前列环素E1对肝动脉碘化油栓塞术后肝纤维化家兔的影响#br#[J]. 实验动物与比较医学, 2020, 40(3): 212-.
[9]	张飞, 党源, 薛来恩, 温福利, 郑和平, 胡德庆. 过表达骨形态发生蛋白4对兔骨髓间充质干细胞增殖与成软骨的影响[J]. 实验动物与比较医学, 2020, 40(2): 87-94.
[10]	卫佳宁, 续国强, 高继萍, 王晓堂, 肖兰飞, 宋国华. 中国仓鼠口腔鳞癌miR-504的表达特征分析[J]. 实验动物与比较医学, 2019, 39(5): 342-348.
[11]	李琰, 孔建军, 陈子奇, 祝聪聪. 短发夹RNA TRPV4基因对脊柱侧弯大鼠模型椎间盘退变的抑制作用[J]. 实验动物与比较医学, 2019, 39(5): 356-363.
[12]	马军, 罗居东, 景文江, 张淑莲, 王娟毅, 范志刚. VEGF基因沉默对人肺癌A549细胞放射增敏作用的体内研究[J]. 实验动物与比较医学, 2019, 39(4): 280-286.
[13]	张志成, 宋庆凯, 黎晓慧, 李娜, 黄鑫, 袁圆, 王璇, 李明学, 代解杰. MPTP诱导树鼩帕金森疾病模型行为学检测方法研究[J]. 实验动物与比较医学, 2019, 39(1): 9-14.
[14]	赵志靖, 第五飞虎, 邓毅恒, 杨利孙. 大鼠脑实质注射血清所致病理改变及其相关机制的研究[J]. 实验动物与比较医学, 2018, 38(6): 412-416.
[15]	杨燕燕, 谢金东, 周建华, 林玮, 王训立. 灵芝多糖对脂多糖诱导的巨噬细胞TLR4/NF-κB通路调控及下游炎症因子的影响[J]. 实验动物与比较医学, 2018, 38(6): 434-439.