无创性延迟肢体缺血预适应对大鼠脑缺血再灌注皮层的保护作用

中国临床药理学与治疗学 ›› 2009, Vol. 14 ›› Issue (2): 144-149.

无创性延迟肢体缺血预适应对大鼠脑缺血再灌注皮层的保护作用

袁恒杰^1,2, 罗琼¹, 朱学慧¹, 于培¹, 李玉梅¹, 吴艳娜¹, 康毅¹, 焦建杰¹, 娄建石¹

¹天津医科大学药理教研室, 天津300070;
²天津医科大学总医院药剂科, 天津300052

收稿日期:2008-11-13 修回日期:2009-01-06 出版日期:2009-02-26 发布日期:2020-10-30
通讯作者: 娄建石, 男, 教授, 博导, 研究方向:心血管药理和临床药理。Tel:022-23542686 　E-mail:jianshilou@sina.com
作者简介:袁恒杰, 女, 博士在读, 主管药师, 研究方向:脑缺血。Tel:022-60363162 　E-mail:hengjieyuan@16.com

Protection of noninvasive delayed limb ischemic preconditioning on cortex against cerebral ischemia reperfusion injury in rats

YUAN Heng-Jie¹, ², LUO Qiong¹, ZHU Xue-hui¹, YU Pei¹, LI Yu-mei¹, WU Yan-na¹, KANG Yi¹, JIAO Jian-jie¹, LOU Jian-shi¹

¹Department of Pharmacology, Tianjin Medical University, Tianjin 300070, China;
²Department of Pharmacy, General Hospital, Tianjin Medical University, Tianjin 300052, China

Received:2008-11-13 Revised:2009-01-06 Online:2009-02-26 Published:2020-10-30

摘要/Abstract

摘要： 目的:研究无创性延迟肢体缺血预适应(NDLIP) 对大鼠脑缺血再灌注损伤的保护作用。方法:通过连续3 d, 每天1 次3 个循环左后肢无创性5 min 缺血、5 min 再灌注, 建立NDLIP 模型。实验分4 组:假手术组(sham) 、缺血再灌注组(I R) 、早期脑缺血预适应+I R 组(ECIP +I R) 、NDLIP +I R 组。观察其对脑缺血再灌注的神经缺损症状, 脑梗死范围, 超氧化物歧化酶(SOD), 谷胱甘肽过氧化物酶(GSH-PX) 活力, 黄嘌呤氧化酶活力(XOD), 丙二醛(MDA) 含量影响。结果:与I R 组相比, ECIP +I R 组及NDLIP +I R 组缺血1 h, 再灌注24 h 后评分有非常显著的降低;脑梗死范围显著减小。与I R 组比较, ECIP +I R 组和NDLIP +I R 组的T-SOD 和Mn-SOD 活力、GSH-PX活力均升高;XOD 活力明显降低, MAD 含量明显减少;ECIP +I R 组和NDLIP +I R 组间差异无统计学意义。结论:NDLIP 可降低I R 对神经的损伤、减小脑梗死范围、提高脑组织抗氧化能力, 减少I R 对脑组织的损伤。

关键词: 远端缺血预适应, 脑缺血预适应, 脑缺血再灌注损伤, 超氧化物歧化酶, 谷胱甘肽过氧化物酶

Abstract: AIM: To study the effects of noninvasive delayed limb ischemic preconditioning (NDLIP) in protecting cerebral tissue from ischemia reperfusion injury.METHODS: NDLIP were performed in rats by three cycle of 5 min ischemia reperfusion of left hind limbs once a day for three days.Animals were divided into four groups :sham group, ischemia reperfusion (I R) group, early cerebral ischemic preconditioning +I R (ECIP +I R) group and NDLIP +I R group.The effects of ischemia reperfusion neurologic defect symptom, cerebral infarction size, superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and xanthine oxidase (XOD), content of malonaldehyde (MDA) in cerebral tissue were observed.RESULTS: Compared with I R group, the neurological score and cerebral infarction size in ECIP +I R group and NDLIP +I R group were markedly lower than those in I R group after ischemic 1 h reperfusion 24 h.Compared with I R group, the activities of T-SOD, Mn-SOD and GSH-PX in ECIP +I R group and NDLIP +I R group increased, while the XOD activity and MDA content obviously decreased, and there were no significant difference between ECIP +I R group and NDLIP +I R group.CONCLUSION: NDLIP could decrease the nerve injury and cerebral infarction size, increase the ability of anti oxidation after I R, and protect cerebral tissue injury of I R.

Key words: remote ischemic preconditioning, brain ischemic preconditioning, cerebral ischemia reperfusion injury, SOD, GSH-PX

中图分类号:

R965.2

袁恒杰, 罗琼, 朱学慧, 于培, 李玉梅, 吴艳娜, 康毅, 焦建杰, 娄建石. 无创性延迟肢体缺血预适应对大鼠脑缺血再灌注皮层的保护作用[J]. 中国临床药理学与治疗学, 2009, 14(2): 144-149.

YUAN Heng-Jie, , LUO Qiong, ZHU Xue-hui, YU Pei, LI Yu-mei, WU Yan-na, KANG Yi, JIAO Jian-jie, LOU Jian-shi. Protection of noninvasive delayed limb ischemic preconditioning on cortex against cerebral ischemia reperfusion injury in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2009, 14(2): 144-149.

参考文献

[1] Murry CE, Jennings RB, Reimer KA.Preconditioning with ischemia:a delay of lethal cell injury in ischemic myocardium[J].Circulation, 1986, 74(5):1124-1136.
[2] Ren C, Gao X, Steinberg GK, et al.Limb remote-preconditioning protects against focal ischemia in rats and contradicts the dogma of therapeutic time windows for preconditioning[J].Neuroscience, 2008, 151(4):1099-1103.
[3] Zhao H, Sapolsky RM, Steinberg GK.Interrupting reperfusion as a stroke therapy:ischemic postconditioning reduces infarct size after focal ischemia in rats[J].J Cereb Blood Flow Metab, 2006, 26(9):1114-1121
[4] Hajrasouliha AR, Tavakoli S, Ghasemi M, et al.Endogenous cannabinoids contribute to remote ischemic preconditioning via cannabinoid CB (2) receptors in the rat heart[J].Eur J Pharmacol, 2008, 579(1 2 3):246-252.
[5] Kanoria S, Jalan R, Davies NA, et al.Remote ischemic preconditioning of the hind limb reduces experimental liver warm ischemia-reperfusion injury[J].Br J Surg, 2006, 93 (6):762-768.
[6] Heidbreder M, Naumann A, Tempel K, et al.Remote vs. ischemic preconditioning:the differential role of mitogenactivated protein kinase pathways[J].Cardiovasc Res, 2008, 78(1):108-115.
[7] Oehmann C, Benz S, Drognitz O, et al.Remote preconditioning reduces microcirculatory disorders in pancreatic ischemia reperfusion injury[J].Pancreas, 2007, 35(4): 45-50.
[8] 李淑娟, 吴艳娜, 康毅, 等.无创性肢体缺血预适应对大鼠心脏的保护作用[J].中国药理学通报,2007, 23(4):527-530.
[9] Longa EZ,Weinstein PR, Carlson S, et al.Reversible middle cerebral artery occlusion without craniotomy in rats [J].Stroke, 1989, 20(1):84-91.
[10] 徐叔云, 卞如濂, 陈修, 主编.药理实验方法学[M].3版.人民卫生出版社, 2002:1067.
[11] Lundy EF, Solik BS, Frank RS, et al.Morphometric evaluation of brain infracts in rats and gerbils[J].J Pharmacological Methods, 1986, 16(3):201-214.
[12] Przyklenk K, Darling CE, Dickson EW, et al.Cardioprotection “ outside the box”:the evolving paradigm of remote preconditioning[J].Basic Res Cardiol, 2003, 98(3):149-157.
[13] Steiger HJ, Hanggi D.Ischaemic preconditioning of the brain, mechanisms and applications[J].Acta Neurochir, 2007, 149(1):1-10.
[14] Zhao HG, Sun XC, Xian XH, et al.The role of nitric oxide in the neuroprotection of limb ischemic preconditioning in rats[J].Neurochem Res, 2007, 32(11):1919-1926.
[15] Narasimhan P, Sugawara T, Liu J, et al.Overexpression of human copper zinc-superoxide dismutase in transgenic animals attenuates the reduction of apurinic apyrimidinic endonuclease expression in neurons after in vitro ischemia and after transient global cerebral ischemia[J].J Neurochem, 2005, 93(2):351-358.
[16] Kondo T, Reaume AG, Huang TT, et al.Reduction of CuZn-superoxide dismutase activity exacerbates neuronal cell injury and edema formation after transient focal cerebral ischemia[J].J Neurosci, 1997, 17 (11):4180-4189.