富氢液对大鼠脑缺血再灌注时磷酸化p38MAPK表达的影响被引量：4

Effects of hydrogen-rich saline on expression of phosphor-p38MAPK during cerebral ischemia-reperfusion in rats

导出

摘要目的评价富氢液对大鼠脑缺血再灌注时磷酸化p38丝裂原激活蛋白激酶（P—p38MAPK）表达的影响。方法健康雄性SD大鼠72只，体重220～250g，采用随机数字表法分为3组（n=24）：假手术组（s组）、脑缺血再灌注组（I／R组）和富氢液组（I／RH组）。I／R组和I／RH组采用线栓法制备大鼠脑缺血再灌注损伤模型，缺血2h，再灌注24h；I／RH组于术前3d及再灌注即刻腹腔注射富氢液（0．6mmol／L）10ml／kg，S组和I／R组注射等容量生理盐水。于再灌注24h时行神经功能缺陷评分，取脑组织，TTC法测定脑梗死体积，计算脑梗死体积百分比；干湿法测定脑含水量；采用TUNEL法检测大脑细胞凋亡情况，计算细胞凋亡指数；采用免疫组化法及Westernblot法检测p38MAPK、和p-p38MAPK的表达。观察脑组织病理学结果。结果与S组比较，I／R组和I／RH组神经功能缺陷评分和细胞凋亡指数升高，脑含水量和脑梗死体积百分比增加，p38MAPK及p-p38MAPK表达上调（P〈0．05）；与I／R组比较，I／RH组神经功能缺陷评分、细胞凋亡指数和脑含水量降低，脑梗死体积百分比减小，p38MAPK及p-p38MAPK表达下调（P〈0．05）。I／RH组脑组织病理学损伤程度较I／R组减轻。结论富氢液通过抑制p-p38MAPK表达，减少细胞凋亡，从而减轻大鼠脑缺血再灌注损伤。 Objective To evaluate the effect of hydrogen-rich saline on the expression of phosphor- p38 mitogen-activated protein kinase （p-p38MAPK） during cerebral ischemia-reperfusion （I/R） in rats. Methods Seventy-two adult male Sprague-Dawley rats, weighing 220-250 g, were randomly divided into 3 groups （n = 20 each） using a random number table： sham operation group （group S） , I/R group and hydrogen-rich saline group （group I/RH）. Cerebral ischcmia was induced in chloral hydrate-anesthetized rats by 2 h middle cerebral artery occlusion in I/R and I/RH groups. The artery was only exposed but not occluded in group S. At 3 days before operation and immediately after onset of reperfusion, hydrogen-rich saline （0.6 mmol/L） 10 ml/kg was intraperitoneally injected in group I/RH, while the equal volume of nor- mal saline was given in S and I/R groups. Neurological deficits were blindly assessed and scored at the end of 24 h reperfusion. The animals were then sacrificed, and brains were removed for microscopic examination and for determination of the cerebral infarct size （ by TTC ） , brain water content, cell apoptosis （ by TUNEL） , and expression of p38MAPk and phosphor-p38MAPK （p-p38MAPK）（by immunohistochemistry and Western blot）. Apoptosis index was calculated. Results Compared with group S, neurological deficit score, apoptosis index, brain water content and cerebral infarct size were significantly increased, and the expression of p38MAPK and p-p38MAPK was up-regulated in I/R and I/RH groups. Compared with group I/R, neurological deficit score, apoptosis index, brain water content and cerebral infarct size were signifi- cantly decreased, and the expression of p38MAPK and p-p38MAPK was down-regulated in group I/RH. The pathological changes of cerebral tissues were significantly attenuated in group I/RH as compared with group I/R. Conclusion Hydrogen-rich saline can reduce cell apoptosis through inhibiting p-p38MAPK ex- pression, thus attenuating cerebral I/R injury in rats.

作者李达艾艳秋金峰何龙张卫

机构地区郑州大学第一附属医院麻醉科河南省高等学校临床医学重点学科开放实验室

出处《中华麻醉学杂志》 CAS CSCD 北大核心 2015年第3期370-372,共3页 Chinese Journal of Anesthesiology

关键词氢再灌注损伤脑丝裂原激活蛋白激酶类 Hydrogen Reperfusion injury Brain Mitogen-activated protein kinases

分类号 R614 [医药卫生—麻醉学]

作者简介通信作者：艾艳秋，E-mail：aiyanqiu82@163．com

引文网络
相关文献

参考文献10

1Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals [ J ]. Nat Med, 2007,13 ( 6 ) : 688-694.
2Fukuda K, Asoh S, Ishikawa M, et al. Inhalation of hydrogen gas suppresses hepatic injury caused by ischemia/reperfusion through reducing oxidative stress[ J]. Biochem Biophys Res Com- mun, 2007,28 ;361 (3) :670-674.
3李登峰,张辉,赵伟,蒋楷,杨曦,宋苏沛,颜明.富氢液对大鼠神经病理性痛的影响[J].中华麻醉学杂志,2014,34(5):570-573. 被引量：3
4Koike N, Takeyoshi I, Ohki S, et al. Effects of adding p38 mito- gen-activated protein-kinase inhibitor to celsior solution in canine heart transplantation from non-heart-beating donors [ J ]. Trans- plantation, 2004,77 (2) : 286-292.
5Gtizel A, R61z R, Nikkhah G, et al. A microsurgical proce- dure for middle cerebral artery occlusion by intraluminal monofil- ament insertion technique in the rat: a special emphasis on the methodology[ J ]. Exp Transl Stroke Med, 2014, 6: 6. doi: 10. 1186/2040-7378-6-6.eCollection 2014.
6del Rey A, Yau HJ, Randolf A, et al. Chronic neuropathic pain like behavior correlates with IL-113 expression and disrupts cytokine interactions in the hippocampus [ J ]. Pain, 2011,152 (12) :2827-2835.
7Yaidikar L, Byna B, Thakur SR, et al. Neuroprotective effect of punicalagin against cerebral ischemia reperfusion-induced oxi- dative brain injury in rats[ J]. Stroke Cerebrovasc Dis, 2014,23 (10) :2869-2878.
8Shi J, Yao F, Zhong C, et al. Hydrogen saline is protective for acute lung ischemia/reperfusion injury in rats [ J ]. Heart Lung Circ,2012,21 (9) :556-563.
9Cai J, Kang Z, Liu K, et al. Neuroprotective effects of hydrogen saline in neonatal hypoxia-ischemia rat model [ J ]. Brain Res, 2009,1256 : 129-137.
10Wang M, Tsai BM, Turrcntine MW, et al. p38mitogen activated protein kinase mediates both death signaling and functional de- pression in the heart [ J ]. Ann Thorae Surg, 2005,80 ( 6 ) : 2235- 2241.

二级参考文献15

1Clausen F, Hanell A, Israelsson C, et al. Neutralization of inte- rleukin-1β reduces cerebral edema and tissue loss and improves late cognitive outcome following traumatic brain injury in mice[Jl. Eur J Neurosci, 2011, 34( 1 ) : 110-123.
2del Rey A, Yau HJ, Randolf A, et al. Chronic neuropathic pain-like behavior correlates with IL-1β expression and disrupts cytokine interactions in the hippocampus [ J ]. Pain, 2011,152 (12) : 2827- 2835.
3Kim HK, Park SK, Zhou JL, et al. Reactive oxygen species (ROS) play an important role in a rat model of neuropathic pain[J]. Pain, 2004, 111(1-2): 116-124.
4Ohsawa I, Ishikawa M, Takahashi K, et al. Hydrogen acts as a the- rapeutic antioxidant by selectively reducing cytotoxic oxygen radicals [J]. Nat Med,2007,13(6) :688-694.
5Xie K, Yu Y, Pei Y, et al. Protective effects of hydrogen gas onmurine polymicrobial sepsis via reducing oxidative stress and HMGB1 release[J]. Shock, 2010, 34(1): 90-97.
6Bennett GJ, Xie YK. A peripheral mononeuropathy in rat that pro- duces disorders of pain sensation like those seen in man [ J . Pain, 1988, 33(1) :87-107.
7Dixon WJ. Efficient analysis of experimental observations[J]. Annu Rev Pharmaeol Toxicol, 1980, 20: 441-462.
8Xie K, Yu Y, Huang Y, et al. Molecular hydrogen ameliorates lipo- polysaccharide-induced acute lung injury in mice through reducing inflammation and apoptosis[ J].Shock, 2012, 37 (5) : 548-555.
9Whitehead KJ, Smith CG, Delaney SA, et al. Dynamic regulation of spinal pro-inflammatory cytokine release in the rat in vivo following peripheral nerve injury[Jl. Brain Behav Immun, 2010, 24(4) : 569- 576.
10Shimazaki J, Matsumoto N, Ogura H, et al. Systemic involvement of high-mobility group box 1 protein and therapeutic effect of anti-high- mobility group box 1 protein antibody in a rat model of crush injury [J]. Shock, 2012,30(6) :634-638.