[1]樊宗兵,童旭辉,李言,等.丙泊酚保护脑缺血再灌注损伤可能与缝隙连接功能的抑制相关[J].南方医科大学学报,2015,(12):1678.
 FAN Zongbing,TONG Xuhui,LI Yan,et al.Protective effect of propofol against cerebral ischemic/reperfusion injury may involveinhibition of gap junction[J].Journal of Southern Medical University,2015,(12):1678.
点击复制

丙泊酚保护脑缺血再灌注损伤可能与缝隙连接功能的抑制相关()
分享到:

《南方医科大学学报》[ISSN:1673-4254/CN:44-1627/R]

卷:
期数:
2015年12期
页码:
1678
栏目:
出版日期:
2015-12-20

文章信息/Info

Title:
Protective effect of propofol against cerebral ischemic/reperfusion injury may involve
inhibition of gap junction
作者:
樊宗兵童旭辉李言于丽陈银玲刘浩昂董淑英
Author(s):
FAN Zongbing TONG Xuhui LI Yan YU Li CHEN Yinling LIU Haoang DONG Shuying
关键词:
脑缺血再灌注损伤丙泊酚蛋白激酶C缝隙连接蛋白43缝隙连接凋亡
Keywords:
cerebral ischemia reperfusion injury propofol PKC Cx43 gap junction apoptosis
摘要:
目的探讨丙泊酚对脑缺血再灌注损伤的保护作用与缝隙连接的关系及其可能机制。方法70只雄性SD大鼠随机分为假
手术(sham)组、缺血再灌注(I/R)组、丙泊酚低剂量(P25,25 mg/kg)组、中剂量(P50,50 mg/kg)组、高剂量(P100, 100 mg/kg)组、甘珀
酸(CBX)干预缺血再灌注(I/R+CBX)组和甘珀酸干预丙泊酚高剂量(P100+CBX)组。采用线栓法制备大鼠大脑中动脉栓塞
(MCAO)模型,脑缺血2 h,再灌注24 h;采用Longa’s 法对大鼠进行神经行为学评分;TTC染色法检测脑梗死体积的变化;
Western blot法检测缝隙连接蛋白43(Cx43)、蛋白激酶C(PKC)以及凋亡相关因子Bax、Bcl-2的蛋白表达变化。结果与缺血再
灌注组相比,除丙泊酚低剂量组外,丙泊酚中、高剂量组神经功能缺损评分和脑梗死体积百分率均明显降低,且高剂量组效果更
佳;甘珀酸可以进一步增强丙泊酚对大鼠脑缺血再灌注损伤的保护作用。Western blot 结果显示,与sham组相比,I/R组Cx43蛋
白表达以及Bax与Bcl-2比值显著增高,而PKC蛋白表达明显降低;丙泊酚高剂量组较I/R组Cx43蛋白表达及Bax与Bcl-2比值
明显降低,PKC蛋白表达显著增多;且甘珀酸可以使丙泊酚的这一作用增强。结论丙泊酚预处理可减轻I/R损伤,其机制可能
与通过PKC信号通路抑制缝隙连接功能及降低Bax/Bcl-2的比值有关。
Abstract:
Objective To investigate the protective effect of propofol against focal cerebral ischemia/reperfusion (I/R) injury in
rats and its relation with gap junction. Methods Seventy adult male SD rats were randomly divided into sham-operated
group, I/R group, low-, moderate-, and high-dose propofol groups (25, 50, 100 mg/kg; P25, P50, P100 groups, respectively), I/R+
CBX group and P100+CBX group. Thread occlusion was used to induce middle cerebral artery occlusion (MCAO) in the mice for
2 h followed by reperfusion for 24 h. Longa’s scores were used to evaluate the neurological behavior of the rats. TTC staining
was used to measure the cerebral infarction volume and Western blotting was performed to detect the expressions of Cx43,
PKC, Bax, and Bcl-2 in the brain of the rats. Results Compared with the I/R group, the rats pretreated with moderate and high
doses of propofol showed significantly reduced neurological behavior scores and cerebral infarction volume percentage, and
the effect was more obvious in high-dose propofol pretreatment group. CBX obviously enhanced the protective effect of propofol
against I/R injury. Compared with those in the sham-operated group, the protein expression of Cx43 and the Bax/Bcl-2 ratio
were increased and the protein expression of PKC was reduced in I/R group, and these changes were significantly reversed by
high-dose propofol pretreatment; the effects of propofol were further enhanced by CBX. Conclusion The protective effect of
propofol against cerebral I/R injury may involve the inhibition of the gap junction via PKC signaling and by reducing the Bax/
Bcl-2 ratio.

参考文献/References:

[1] Eshah NF. Lifestyle and health promoting behaviours in Jordanian
subjects without prior history of coronary heart disease[J]. Int J
Nurs Pract, 2011, 17(1): 27-35.
[2] Yang S, Chou WP, Pei L. Effects of propofol on renal ischemia/
reperfusion injury in rats[J]. Exp Ther Med, 2013, 6(5): 1177-83.
[3] Ye L, Luo CZ, Mccluskey SA, et al. Propofol attenuates hepatic
ischemia/reperfusion injury in an in vivo rabbit model[J]. J Surg
Res, 2012, 178(2): e65-70.
[4] Zhou R, Yang Z, Tang X, et al. Propofol protects against focal
cerebral ischemia via inhibition of microglia-mediated proinflammatory
cytokines in a rat model of experimental stroke[J]. PLoS
One, 2013, 8(12): e82729.
[5] Homkajorn B, Sims NR, Muyderman H. Connexin 43 regulates
astrocytic migration and proliferation in response to injury[J].
Neurosci Lett, 2010, 486(3): 197-201.
[6] Wang N, De Vuyst E, Ponsaerts R, et al. Selective inhibition of
Cx43 hemichannels by Gap19 and its impact on myocardial
ischemia/reperfusion injury[J]. Basic Res Cardiol, 2013, 108(1):
309.
[7] Luo C, Yuan D, Li X, et al. Propofol attenuated acute kidney injury
after orthotopic liver transplantation via inhibiting gap junction
composed of connexin 32[J]. Anesthesiology, 2015, 122(1): 72-86.
[8] 肖峰, 周晓清, 李元涛, 等. 异丙酚对大鼠缺血再灌注海马区Bax和
Bcl-2 表达的影响[J]. 华中科技大学学报: 医学版, 2010, 39(1):
113-5, 119.
[9] Tong X, Han X, Yu B, et al. Role of gap junction intercellular
communication in testicular leydig cell apoptosis induced by
oxaliplatin via the mitochondrial pathway[J]. Oncol Rep, 2015, 33
(1): 207-14.
[10]Yin D, Zhou C, Kusaka I, et al. Inhibition of apoptosis by
hyperbaric Oxygen in a rat focal cerebral ischemic model[J]. J
Cereb Blood Flow Metab, 2003, 23(7): 855-64.
[11]Ye XH, Wu Y, Guo PP, et al. Lipoxin a4 analogue protects brain and
reduces inflammation in a rat model of focal cerebral ischemia
reperfusion[J]. Brain Res, 2010, 1323(15): 174-83.
[12]Zhang YM, Xu H, Sun H, et al. Electroacupuncture treatment
improves neurological function associated with regulation of tight
junction proteins in rats with cerebral ischemia reperfusion injury
[J]. Evid Based Complement Alternat Med, 2014, 15(6): 989340.
[13]Ji FT, Liang JJ, Miao LP, et al. Propofol postconditioning protects
the blood brain barrier by decreasing matrix metalloproteinase9 and
aquaporin4 expression and improves the neurobehavioral outcome
in a rat model of focal cerebral ischemiareperfusion injury[J]. Mol
Med Rep, 2015, 12(2): 2049-55.
[14]Wang H, Liu S, Wang H, et al. The effect of propofol postconditioning
on the expression of K(+ )-Cl(-)-co-transporter 2 in
GABAergic inhibitory interneurons of acute ischemia/reperfusion
injury rats[J]. Brain Res, 2015, 1597(16): 210-9.
[15]Yue ZY, Dong H, Wang YF, et al. Propofol prevents neuronal
mtDNA deletion and cerebral damage due to ischemia/reperfusion
injury in rats[J]. Brain Res, 2015, 1594(8): 108-14.
[16]宋春雨, 陶涛, 崔晓光, 等. 丙泊酚对全脑缺血/再灌注损伤大鼠保护
作用研究[J]. 国际麻醉学与复苏杂志, 2011, 32(4): 393-7.
[17]Giaume C, Orellana JA, Abudara V, et al. Connexin-based channels
in astrocytes: how to study their properties[J]. Methods Mol Biol,
2012, 814: 283-303.
[18]董淑英, 童旭辉, 蒋国君, 等. 星形胶质细胞中缝隙连接蛋白connexin
43 的表达及其功能调控[J]. 南方医科大学学报, 2012, 32(10):
1423-6.
[19]Schulz R, Görge PM, Görbe A, et al. Connexin 43 is an emerging
therapeutic target in ischemia/reperfusion injury, cardioprotection
and neuroprotection[J]. Pharmacol Ther, 2015, 153(7): 90-106.
[20]张凤云, 赵炎, 吴玉林. 蛋白激酶C在脑缺血再灌注损伤中的作用[J].
中国临床药理学与治疗学, 2013, 18(4): 461-8.
[21]Shan H, Wei J, Zhang M, et al. Suppression of PKCε-mediated
mitochondrial connexin 43 phosphorylation at serine 368 is
involved in myocardial mitochondrial dysfunction in a rat model of
dilated cardiomyopathy[J]. Mol Med Rep, 2015, 11(6): 4720-6.
[22]Sanderson TH, Reynolds CA, Kumar R, et al. Molecular mechanisms
of ischemia-reperfusion injury in brain: pivotal role of the
mitochondrial membrane potential in reactive Oxygen species
Generation[J]. Mol Neurobiol, 2013, 47(1): 9-23.
[23]Huang X, Choi JK, Park SR, et al. GM-CSF inhibits apoptosis of
neural cells via regulating the expression of apoptosis-related
proteins[J]. Neurosci Res, 2007, 58(1): 50-7.

相似文献/References:

[1]谭红鹰,操隆辉,黄婉,等.七氟醚及丙泊酚分别复合瑞芬太尼诱导用于纤支镜气管插管比较[J].南方医科大学学报,2010,(08):1857.
 TAN Hong-ying,CAO Long-hui,HUANG Wan,et al.Comparison of sevoflurane and propofol in combined anesthesia induction with remifentanilfor tracheal intubation with fiberoptic bronchoscope[J].Journal of Southern Medical University,2010,(12):1857.
[2]侯德仁,沙地克·沙吾提,邓锦凤,等.意向运动疗法对大鼠脑缺血再灌注损伤后NT-3 及GAP-43 表达的影响[J].南方医科大学学报,2011,(08):1401.
[3]刘高望,史永胜,徐建设,等.丙泊酚复合芬太尼麻醉在经阴道超声引导取卵术中的应用[J].南方医科大学学报,2004,(11):1304.
 LIU Gao-wang,SHI Yong-sheng,XU Jian-she,et al.Intravenous propofol combined with fentanyl for anesthesia during ultrasound-guided transvaginal oocyte retrieval[J].Journal of Southern Medical University,2004,(12):1304.
[4]尧永华,邬子林.瑞芬太尼复合丙泊酚静脉麻醉用于老年患者结肠镜检查的临床观察[J].南方医科大学学报,2005,(06):715.
 YAO Yong-hua,WU Zi-lin.Clinical investigation of total intravenous anesthesia with remifentanil and propofol for colonoscopy in the elderly[J].Journal of Southern Medical University,2005,(12):715.
[5]杨晶晶,林春水,古妙宁,等.脑摄取平衡时丙泊酚对犬脑不同区域GAT-1 mRNA和GAD65mRNA的影响[J].南方医科大学学报,2012,(10):1469.
[6]许德奖,杨威,赵国栋.丙泊酚与气体麻醉对老年患者术后认知功能障碍的影响:Meta分析[J].南方医科大学学报,2012,(11):1623.
[7]张砡,李俣,李伟光,等.丙泊酚对新生大鼠大脑皮层星形胶质细胞合成凝血酶敏感蛋白1的影响[J].南方医科大学学报,2013,(09):1316.
[8]汪 威,林春水,张雅静,等.丙泊酚对肿瘤细胞肺转移及E钙粘蛋白、β-连环蛋白表达的影响[J].南方医科大学学报,2015,(06):852.
[9]张雅静,林春水,汪威,等.丙泊酚对荷瘤大鼠肿瘤肺转移及MTA1和Wnt1表达的影响[J].南方医科大学学报,2014,(07):1011.
[10]梁芳果,欧阳铭文,王海棠.BIS反馈闭环路靶控输注右美托咪定可减少丙泊酚用量[J].南方医科大学学报,2015,(10):1497.

更新日期/Last Update: 1900-01-01