远隔缺血预适应对大鼠局灶性脑缺血后诱导型一氧化氮合酶的影响

doi:10.3969/j.issn.1006-7795.2014.03.011

首都医科大学学报 ›› 2014, Vol. 35 ›› Issue (3): 315-319.doi: 10.3969/j.issn.1006-7795.2014.03.011

远隔缺血预适应对大鼠局灶性脑缺血后诱导型一氧化氮合酶的影响

闫峰, 尹洁, 罗玉敏, 李森, 王玉兰, 赵咏梅

首都医科大学宣武医院北京市老年病医疗研究中心神经变性病教育部重点实验室脑血管病转化医学北京市重点实验室, 北京 100053

收稿日期:2014-02-17 出版日期:2014-06-21 发布日期:2014-06-14
通讯作者: 赵咏梅，E-mail：yongmeizhao@hotmail.com E-mail:yongmeizhao@hotmail.com
基金资助:
北京市自然科学基金（7122036）；脑血管病转化医学北京市重点实验室开放课题（2013NXGZ03）资助。

Effect of remote ischemic preconditioning on inducible nitric oxide synthase expression following focal cerebral ischemia in rat

Yan Feng, Yin Jie, Luo Yumin, Li Sen, Wang Yulan, Zhao Yongmei

Xuanwu Hospital, Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory of Neurodegenerative Diseases of Ministry of Education, Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing 100053, China

Received:2014-02-17 Online:2014-06-21 Published:2014-06-14
Supported by:
This study was supported by Natural Science Foundation of Beijing(7122036), Open Project of Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases(2013NXGZ03).

摘要/Abstract

摘要：

目的研究远隔缺血预适应（remote ischemic preconditioning，RIPC）对大鼠脑缺血再灌注后诱导型一氧化氮合酶（inducible nitric oxide synthase，iNOS）表达的影响，以探讨RIPC保护脑缺血损伤的相关机制。方法应用线栓法制作大脑中动脉栓塞（middle cerebral artery occlusion，MCAO）模型，将21只健康雄性SD大鼠采用数字表法随机分为3组：假手术组（sham，n=7），MCAO组（n=7），RIPC+MCAO组（n=7）。在MCAO手术前连续3 d，进行远隔肢体缺血预适应处理（双侧股动脉夹闭10 min/放开10 min，每天3次）。在缺血2 h-再灌注24 h后进行神经功能评分，TTC染色检测脑梗死体积，采用Western blotting方法检测梗死侧脑组织的iNOS蛋白表达水平。结果 1）在MCAO手术过程中，3组实验动物的生理指标均在正常范围内，且组间差异无统计学意义。与sham组相比，MCAO组大鼠再灌注24 h时神经功能缺损评分显著升高、脑梗死体积明显增大（P<0.05）。而RIPC+MCAO组大鼠神经功能较MCAO组大鼠得到明显改善、脑梗死体积显著减少（P< 0.05）。2）再灌注24 h时，与sham组相比，MCAO组大鼠脑梗死侧iNOS蛋白表达显著增加（P<0.05）。与MCAO组相比，RIPC+MCAO组大鼠脑梗死侧iNOS蛋白表达显著降低（P<0.05）。结论 RIPC处理对大鼠脑缺血损伤具有保护作用，其机制与降低脑缺血大鼠脑内iNOS蛋白表达有关。

关键词: 远隔缺血预适应, 脑缺血, 诱导型一氧化氮合酶

Abstract:

Objective The objective of this study is to investigate the effect of remote ischemic preconditioning(RIPC) on the expression of inducible nitric oxide synthase(iNOS) in ischemia-reperfusion rats to explore the relative mechanisms of RIPC on cerebral ischemic injury. Methods Middle cerebral artery occlusion(MCAO) operation was performed using suture method. Twenty-one male Sprague Dawley rats were divided randomly into three groups: sham group(n=7), MCAO group(n=7) and RIPC+MCAO group(n=7). Three cycles of RIPC induced by temporarily occluding the bilateral femoral arteries(10 minutes) prior to 10 minutes of reperfusion were given three times a day for 3 days before the animal received MCAO surgery. After 2 h ischemia and 24 h reperfusion, neurological deficits were evaluated and brain infarct volume was measured by 2, 3, 5-triphenyltetrazolium chloride(TTC) staining. The expression of iNOS in ipsilateral hemisphere was determined quantitatively by Western blotting analysis. Results 1 The physiological parameters of the three groups of rats were in normal arrange showing no statistically significant difference. The neurological deficit score and brain infarct volume in MCAO group rats increased significantly compared with those of sham group at 24 h after reperfusion(P<0.05), which were significantly decreased by RIPC+MCAO treatment(P<0.05). 2 The expression of iNOS in ipsilateral hemispheres of MCAO group rats at 24 h after reperfusion increased significantly compared with that of sham group rats(P<0.05) while the expression of iNOS in RIPC+MACAO group reduced remarkably compared with that of MCAO group(P<0.05). Conclusion RIPC treatment protects against cerebral ischemic injury in rats, which might be related to the decreased expression of iNOS in the ischemic brain.

Key words: remote ischemic preconditioning, cerebral ischemia, inducible nitric oxide synthase

中图分类号:

R743.31

闫峰, 尹洁, 罗玉敏, 李森, 王玉兰, 赵咏梅. 远隔缺血预适应对大鼠局灶性脑缺血后诱导型一氧化氮合酶的影响[J]. 首都医科大学学报, 2014, 35(3): 315-319.

Yan Feng, Yin Jie, Luo Yumin, Li Sen, Wang Yulan, Zhao Yongmei. Effect of remote ischemic preconditioning on inducible nitric oxide synthase expression following focal cerebral ischemia in rat[J]. Journal of Capital Medical University, 2014, 35(3): 315-319.

参考文献

[1] Fisher M. New approaches to neuroprotective drug development[J]. Stroke, 2011, 42(1 suppl):S24-27.
[2] Erling Junior N, Montero E F, Sannomiya P, et al. Local and remote ischemic preconditioning protect against intestinal ischemic/reperfusion injury after supraceliac aortic clamping[J]. Clinics(Sao Paulo), 2013, 68(12):1548-1554.
[3] Puyal J, Ginet V, Clarke P G. Multiple interacting cell death mechanisms in the mediation of excitotoxicity and ischemic brain damage: a challenge for neuroprotection[J]. Prog Neurobiol, 2013, 105:24-48.
[4] Terpolilli N A, Moskowitz M A, Plesnila N. Nitric oxide: considerations for the treatment of ischemic stroke[J]. J Cereb Blood Flow Metab, 2012, 32(7):1332-1346.
[5] Roberts B W, Mitchell J, Kilgannon J H, et al. Nitric oxide donor agents for the treatment of ischemia/reperfusion injury in human subjects: a systematic review[J]. Shock, 2013, 39(3):229-239.
[6] 李森, 闫峰, 闫颖, 等.大鼠局灶性脑缺血损伤后半暗带区锌离子的变化[J].中国神经免疫学和神经病学杂志, 2012, 19(3):175-178.
[7] Belayev L, Alonso O F, Busto R, et al. Middle cerebral artery occlusion in the rat by intraluminal suture. Neurological and pathological evaluation of an improved model[J]. Stroke, 1996, 27(9):1616-1622, discussion 1623.
[8] 李芳, 刘向荣, 闫峰, 等.局部亚低温对大鼠脑缺血再灌注基质金属蛋白酶9及细胞外基质蛋白表达的影响[J].首都医科大学学报, 2013, 34(1):58-63.
[9] 何洁, 吉训明, 李思颉, 等.远隔缺血预适应对脑缺血疗效的SPECT评价[J].首都医科大学学报, 2013, 34(1):6-10.
[10] 李如娟, 曹金强, 杨金波, 等.肢体远隔缺血预适应对缺血性脑血管病患者的脑保护作用[J].中国脑血管病杂志, 2012, 9(7):337-341.
[11] 卢晓航.一氧化氮在脑缺血中的作用及机制研究进展[J].现代预防医学, 2007, 34(7):1286-1287.
[12] Koskenkorva-Frank T S, Weiss G, Koppenol W H, et al. The complex interplay of iron metabolism, reactive oxygen species, and reactive nitrogen species: insights into the potential of various iron therapies to induce oxidative and nitrosative stress[J]. Free Radic Biol Med, 2013, 2(65C):1174-1194.
[13] Godínez-Rubí M, Rojas-Mayorquín A E, Ortuo-Sahagún D. Nitric oxide donors as neuroprotective agents after an ischemic stroke-related inflammatory reaction[J]. Oxid Med Cell Longev, 2013, 2013:297357.
[14] He F, Ye B, Chen J, et al. Influence of hepatocyte growth factor on iNOS, NO and IL-1β in the cerebrum during cerebral ischemia/reperfusion in rats[J]. Zhong Nan Da Xue Xue Bao Yi Xue Ban, 2014, 39(1):23-29.
[15] 李健, 党辉, 沙晶, 等.脑缺血/再灌注前后一氧化氮合酶在脑皮质中的表达[J].疑难病杂志, 2012, 11(4):280-282.
[16] 张洁, 邢岩.肿瘤坏死因子α诱导脑血管内皮细胞产生病理性一氧化氮的实验研究[J].中国脑血管病杂志, 2011, 8(8):429-432.
[17] Zhou M, Wang C M, Yang W L, et al. Microglial CD14 activated by iNOS contributes to neuroinflammation in cerebral ischemia[J]. Brain Res, 2013, 19(1506):105-114.

远隔缺血预适应对大鼠局灶性脑缺血后诱导型一氧化氮合酶的影响

Effect of remote ischemic preconditioning on inducible nitric oxide synthase expression following focal cerebral ischemia in rat

PDF

可视化

被引次数

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]	房亚兰, 杨楠, 赵咏梅, 黄语悠, 李锦程, 段云霞, 高利, 罗玉敏. 大黄酚对局灶性脑缺血再灌注小鼠缺血半暗带区HIF-1α与VEGF表达的影响[J]. 首都医科大学学报, 2021, 42(2): 219-224.
[2]	杨楠, 丁锚, 闫峰, 师文娟, 黄语悠, 赵咏梅. 远隔缺血预适应对脑缺血再灌注损伤大鼠缺血半暗带区PERK/p-eIF2α通路及自噬的影响[J]. 首都医科大学学报, 2021, 42(2): 225-231.
[3]	丁锚, 杨楠, 黄语悠, 师文娟, 闫峰, 赵咏梅, 刘克建. 线粒体活性氧自由基抑制剂R(+)-普拉克索对脑缺血再灌注损伤大鼠JAK2-STAT3通路及炎性因子TNF-α的影响[J]. 首都医科大学学报, 2021, 42(2): 232-238.
[4]	杨楠, 丁锚, 黄语悠, 房亚兰, 师文娟, 赵咏梅. 一氧化氮在大鼠短暂性局灶性脑缺血损伤中对神经生长因子和脑源性神经营养因子表达的影响[J]. 首都医科大学学报, 2020, 41(6): 908-913.
[5]	王明洋, 孙争宇, 张丽, 李雅莉, 李林, 张兰. 山茱萸环烯醚萜苷对脑缺血再灌注大鼠线粒体损伤的影响[J]. 首都医科大学学报, 2020, 41(3): 385-390.
[6]	房亚兰, 黄语悠, 赵咏梅, 师文娟, 李锦程, 段云霞, 高利, 罗玉敏. 大黄酚对局灶性脑缺血再灌注小鼠Beclin1及Bax的作用[J]. 首都医科大学学报, 2019, 40(5): 703-708.
[7]	黄语悠, 房亚兰, 师文娟, 刘克建, 赵咏梅, 丁锚, 罗玉敏. 一氧化氮清除剂Carboxy-PTIO对短暂性局灶性脑缺血大鼠PERK/p-eIF2α通路的调节作用[J]. 首都医科大学学报, 2019, 40(5): 709-714.
[8]	张杨, 马展鸿, 蒋涛. 心房颤动患者左房耳形态与血栓及短暂性脑缺血发作关系的研究[J]. 首都医科大学学报, 2019, 40(5): 776-780.
[9]	师文娟, 赵咏梅, 戚智锋, 黄语悠, 房亚兰, 刘克建. 常压高浓度氧对脑缺血-再灌注大鼠缺血核心区核转录因子-κB的适度调节作用[J]. 首都医科大学学报, 2018, 39(3): 349-354.
[10]	黄语悠, 房亚兰, 师文娟, 刘克建, 赵咏梅. 一氧化氮合酶抑制剂N-硝基-L-精氨酸甲酯对局灶性脑缺血再灌注大鼠缺血半暗带区细胞自噬的影响[J]. 首都医科大学学报, 2018, 39(3): 355-359.
[11]	房亚兰, 黄语悠, 赵咏梅, 李锦程, 段云霞, 高利, 罗玉敏. 大黄酚对局灶性脑缺血再灌注小鼠脑组织p-CREB、BDNF和p-STAT3的影响[J]. 首都医科大学学报, 2018, 39(3): 360-365.
[12]	房亚兰, 尹洁, 刘克建, 赵咏梅. 脑缺血再灌注损伤中自由基与锌离子的相互作用[J]. 首都医科大学学报, 2018, 39(3): 373-377.
[13]	陆跃, 刘建红, 赵晖, 常佳慧, 相阳阳, 张秋霞. 侯氏黑散对脑缺血大鼠神经导向因子及Rho GTP酶的影响[J]. 首都医科大学学报, 2017, 38(6): 891-896.
[14]	王潇, 苏跃, 李天佐, 赵斌江. 胆碱能抗炎通路对大鼠脑缺血再灌注损伤的影响[J]. 首都医科大学学报, 2017, 38(3): 342-347.
[15]	师文娟, 戚智锋, 刘克建. 常压高浓度氧下调电压依赖性阴离子通道蛋白对脑缺血-再灌注损伤大鼠的保护作用[J]. 首都医科大学学报, 2017, 38(1): 42-46.