[1]黄　坦　黄书岚　陈谦学.NaHS抑制Nox4 和 p22p hox的表达保护小鼠脑缺血再灌注损伤[J].中国临床神经外科杂志,2016,(09):545-548.[doi:10.13798/j.issn.1009-153X.2016.09.011]
　HUANG Tan,HUANG Shu-lan,CHEN Qian-xue..NaHS induces neuroprotection against cerebral ischemia reperfusion injury by inhibiting Nox4 and p22phox expressions in cerebral tissues in mice[J].,2016,(09):545-548.[doi:10.13798/j.issn.1009-153X.2016.09.011]
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NaHS抑制Nox4 和 p22p hox的表达保护小鼠脑缺血再灌注损伤()
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《中国临床神经外科杂志》[ISSN:1009-153X/CN:42-1603/TN]

卷:
期数:
2016年09期
页码:
545-548
栏目:
论著
出版日期:
2016-09-25

文章信息/Info

Title:
NaHS induces neuroprotection against cerebral ischemia reperfusion injury by inhibiting Nox4 and p22phox expressions in cerebral tissues in mice
文章编号:
1009-153X（2016）09-0545-04
作者:
黄　坦　黄书岚　陈谦学
430060 武汉，武汉大学人民医院神经外科[黄　坦（硕士研究生，现在泰康同济（武汉）医院工作）、黄书岚、陈谦学]
Author(s):
HUANG Tan;  HUANG Shu-lan;  CHEN Qian-xue.
Department of Neurosurgery, Renmin Hospital, Wuhan University, Wuhan 430060, China
关键词:
脑缺血再灌注损伤; NaHS; NOX4; p22phox; 小鼠
Keywords:
Ischemia reperfusion injury;  NaSH;  NOX4;  p22p hox;  Expression;  Neuroprotection
分类号:
R 743; Q 786
DOI:
10.13798/j.issn.1009-153X.2016.09.011
文献标志码:
A
摘要:
目的 探讨NaHS对小鼠脑缺血再灌注损伤的作用及机制。方法 将105只C57小鼠随机分成假手术组（15只）、模型组（45只）和NaHS组（45只），后两组按时间点24 h、48 h、72 h再分为3个亚组，每亚组15只。采用线栓法阻塞左侧大脑中动脉制作脑缺血再灌注损伤模型。NaSH组造模前30 min、造模后24、48 h各腹腔注射NaHS一次，100 μmol/kg；假手术组和模型组注射等体积生理盐水。采用Berderson改良量表评估神经功能，采用TTC染色法测量脑梗死体积，分别用PCR和免疫印迹法检查缺血脑组织还原型烟酰胺腺嘌呤二核苷酸磷酸氧化酶4和p22-phox mRNA和蛋白表达水平。结果 与假手术组比，造模后24、48、72 h，模型组脑梗死体积均明显增高（P<0.05），神经功能均显著变差（P<0.05），缺血脑组织NOX4和p22-phox mRNA和蛋白表达水平均明显增高（P<0.05），造模后48 h达高峰。而与模型组比，造模后24、48、72 h，NaHS组脑梗死体积均明显降低（P<0.05），神经功能均显著改善（P<0.05），缺血脑组织NOX4和p22-phox mRNA和蛋白表达水平均明显降低（P<0.05）。结论 NaHS可能通过抑制Nox4 和 p22p hox的表达保护小鼠脑缺血再灌注损伤；伤后48 h可能是脑缺血再灌注损伤发展的一个关键点。
Abstract:
Objective To investigated the effect of NaHS on cerebral tissues injured by ischemia-reperfusion (IR) injury. Methods One hundred and five mice were randomly divided into three groups i.e. Sham group (n=15), IR group (n=45), NaHS treatment group (n=45) in which the animals received intraperitoneal injection of 100 μmol/kg NaHS 30 minutes before and 24 and 48 hours after IR. The animals in IR and NaHS groups were randomly divided again into 3 subgroups respectively according to the time to sacrifice the animals. The neurological deficit scale was performed before sacrificing the animals in all the groups. The volumes of infarct cerebral tissues were determined. The expressions of NADPH oxidase 4 (NOX4) and p22p hox mRNA and proteins in the injured cerebral tissues were determined respectively by real-time PCR and western blot. Results The levels of Nox4 and p22p hox expressions in the injured cerebral tissues and the neurological deficit scale scores were significantly higher in IR group than those in NaHS group respectively 24, 48 and 72 hours after IR injury (P<0.05), where were significantly higher respectively than those in sham group (P<0.05). The volumes of infarct cerebral tissues were significantly bigger in IR group than those in NaHS group respectively 24, 48 and 72 hours after IR injury (P<0.05), which were significantly bigger respectively than that in sham group (P<0.05). The volume of infarct cerebral tissues, neurological deficit scale scores and the levels of NOX4 and p22p hox expressions in the injured cerebral tissues reached the tops 48 hours after IR injury compared to those 24 and 72 hours after IR injury (P<0.01). Conclusions It is suggested that NaHS neuroprotection against cerebral IR injury was realized probably by inhibiting NOX4 and p22p hox expressions in the injured cerebral tissue. IR-induced cerebral injury may reach the top 48 hours after IR and then gradually decrease.

参考文献/References:

[1]Tu JV. Reducing the global burden of stroke: interstroke [J]. Lancet, 2010, 376: 74-75.
[2] Brouns R, De Deyn PP. The complexity of neurobiological processes in acute ischemic stroke [J]. Clin Neurol Neuro- surg, 2009, 111: 483-495.
[3] Wang Y, Jia J, Ao G, et al. Hydrogen sulfide protects blood- brain barrier integrity following cerebral ischemia [J]. J Neurochem, 2014, 129: 827-838.
[4] Radermacher KA, Wingler K, Langhauser F, et al. Neuro- protection after stroke by targeting NOX4 as a source of oxidative stress [J]. Antioxid Redox Signal, 2013, 18(12): 1418-1427.
[5] Pan LL, Liu XH, Shen YQ, et al. Inhibition of NADPH oxi- dase 4-related signaling by sodium hydrosulfide attenuates myocardial fibrotic response [J]. Int J Cardiol, 2013, 168: 3770-3778.
[6] Li L, Rose P, Moore PK. Hydrogen sulfide and cell signa- ling [J]. Annu Rev Pharmacol Toxicol, 2011, 51: 169-187.
[7] Ren C, Du A, Li D, et al. Dynamic change of hydrogen sulfide during global cerebral ischemia-reperfusion and its effect in rats [J]. Brain Res, 2010, 1345: 197-205.
[8] Wang L, Lu Y, Deng S, et al. SHPS-1 deficiency induces robust neuroprotection against experimental stroke by atte- nuating oxidative stress [J]. J Neurochem, 2012, 122: 834- 843.
[9] Wang L, Deng S, Lu Y, et al. Increased inflammation and brain injury after transient focal cerebral ischemia in acti- vating transcription factor 3 knockout mice [J]. Neuros- cience, 2012, 220: 100-108.
[10] ?owicka E, Be?towski J. Hydrogen sulfide (H2S) - the third gas of interest for pharmacologists [J]. Pharmacol Rep, 2007, 59: 4-24.
[11] Nicholson CK, Calvert JW. Hydrogen sulfide and ischemia- reperfusion injury [J]. Pharmacol Res, 2010, 62: 289-297.
[12] Li L, Moore PK. Putative biological roles of hydrogen sulfide in health and disease: a breath of not so fresh air [J]. Trends Pharmacol Sci, 2008, 29: 84–90.
[13] Infanger DW, Sharma RV, Davisson RL. NADPH oxidases of the brain: distribution, regulation, and function [J]. Antioxid Redox Signal, 2006, 8: 1583-1596.
[14] Ambasta RK, Kumar P, Griendling KK, et al. Direct interac- tion of the novel Nox proteins with p22phox is required for the formation of a functionally active NADPH oxidase [J]. J Biol Chem, 2004, 279: 45935-45941.
[15] Martyn KD, Frederick LM, von Loehneysen K, et al. Func- tional analysis of Nox4 reveals unique characteristics com- pared to other NADPH oxidases [J]. Cell Signal, 2006, 18: 69-82.
[16] Flamm ES, Demopoulos HB, Seligman ML, et al. Free radi- cals in cerebral ischemia [J]. Stroke 1978, 9: 445-447.
[17] Marchi S, Giorgi C, Suski JM, et al. Mitochondria-ros cross- talk in the control of cell death and aging [J]. J Signal Transduct, 2012, 2012: 329635.
[18] Luo Y, Yang X, Zhao S, et al. Hydrogen sulfide prevents OGD/R-induced apoptosis via improving mitochondrial dysfunction and suppressing an ROS-mediated caspase-3 pathway in cortical neurons [J]. Neurochem Int, 2013, 63: 826-831.

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备注/Memo

备注/Memo:
基金项目：湖北省自然科学基金（2011CHB027）；武汉市科技攻关项目（201060938363-02）
通讯作者：黄书岚，E-mail：huang_shulan@msn.com
更新日期/Last Update: 2016-09-30