缝隙连接在缺血后处理保护大鼠脑缺血再灌注损伤中的作用及可能机制

中国临床药理学与治疗学 ›› 2014, Vol. 19 ›› Issue (8): 841-845.

• 基础研究 • 下一篇

缝隙连接在缺血后处理保护大鼠脑缺血再灌注损伤中的作用及可能机制

焦浩, 童旭辉, 董淑英, 谷昱琛, 余彬彬, 于丽

蚌埠医学院药学系药理学教研室,安徽省生化药物工程技术研究中心,蚌埠 233030,安徽

收稿日期:2013-10-24 修回日期:2014-06-12 出版日期:2014-08-26 发布日期:2014-08-26
通讯作者: 董淑英,女,博士,副教授,研究方向:心脑血管药理学。 Tel: 0552-3150182 E-mail: bbmcdsy@126.com
作者简介:焦浩,男,在读研究生,研究方向:心脑血管药理学。 Tel: 15056398327 E-mail: jiaohaoy@163.com
基金资助:
国家自然科学基金项目(81001457); 安徽省自然科学基金项目(1408085MH176)

Effect of gap junction in ischemic post-conditioning on cerebral ischemic-reperfusion injury in rats and its associated mechanism

JIAO Hao, TONG Xu-hui, DONG Shu-ying, GU Yu-chen, YU Bin-bin, YU Li

Department of Pharmacology, Faculty of Pharmacy, Bengbu Medical College, Anhui Engineering Technology Research Center of Biochemical Pharmaceuticals, Bengbu 233000, Anhui, China

Received:2013-10-24 Revised:2014-06-12 Online:2014-08-26 Published:2014-08-26

摘要/Abstract

摘要： 目的探讨缝隙连接在缺血后处理保护大鼠脑缺血再灌注损伤中的作用及其可能的机制。方法 60只雄性SD大鼠随机分为假手术(sham)组、缺血再灌注(ischmia/reperfusion, I/R)组、缺血后处理(ischemic post-conditioning, IPO)组、甘珀酸(carbenoxolone, CBX)干预缺血再灌注(I/R+CBX)组和甘珀酸干预缺血后处理(IPO+CBX)组。采用线栓法建立大鼠大脑中动脉栓塞模型;Longa's法进行神经功能评分;TTC染色法和HE染色法分别检测大鼠脑梗死体积和脑组织形态学变化;Western Blot法检测脑组织中缝隙连接蛋白43(Cx43)、蛋白激酶C(PKC)蛋白的表达。结果与sham组相比,I/R组神经功能评分显著增高,脑梗死体积增大,细胞排列紊乱、胞核固缩等组织形态学改变显著;IPO可使I/R组损伤减轻;CBX可以进一步增强IPO对I/R损伤的保护作用。Western Blot结果显示,I/R组较sham组Cx43表达增多,PKC表达降低;IPO组较I/R组Cx43表达降低(P<0.01),PKC表达增高(P<0.01),同时,IPO+CBX组较IPO组也有类似的改变。结论 IPO可通过抑制缝隙连接而减轻I/R损伤,其机制可能与影响PKC蛋白的表达有关。

关键词: 缺血后处理, 蛋白激酶C, 缝隙连接蛋白43, 缝隙连接

Abstract: AIM: To investigate the effect of gap junction in ischemic post-conditioning on cerebral ischemic-reperfusion injury in rats. METHODS: Sixty adult male SD rats were randomly divided into sham group, I/R group, IPO group, I/R+CBX group and IPO+CBX group. Thread occlusion method was used to make MCAO model. Neurological scores of rat were evaluated by Longa' score. Infarct volume of brain tissue was measured by TTC staining. Histopathology of cerebral tissue was detected by HE staining. The expressions of Cx43 and PKC protein were detected by Western Blot. RESULTS: In I/R group, neurological deficit scores decreased, cerebral infarction area increased and histopathology changed significantly, while similar changes did not found in sham group. IPO has protective effect on I/R injury. Similarly, CBX increased the protection of IPO on I/R injury obviously. Results of Western Blot showed, in I/R group, Cx43 protein increased significantly and PKC decreased compared to the sham group (P<0.01). Meanwhile, in IPO group Cx43 protein decreased extremely and PKC increased compared to I/R group. Similarly, in IPO+CBX group Cx43 protein decreased significantly and PKC increased compared to IPO group. CONCLUSION: IPO has protective effect on I/R injury through the gap junction, which may be associated with the change of PKC protein.

Key words: ischemic post-conditioning, PKC, Cx43, gap junction

中图分类号:

R965.2

焦浩, 童旭辉, 董淑英, 谷昱琛, 余彬彬, 于丽. 缝隙连接在缺血后处理保护大鼠脑缺血再灌注损伤中的作用及可能机制[J]. 中国临床药理学与治疗学, 2014, 19(8): 841-845.

JIAO Hao, TONG Xu-hui, DONG Shu-ying, GU Yu-chen, YU Bin-bin, YU Li. Effect of gap junction in ischemic post-conditioning on cerebral ischemic-reperfusion injury in rats and its associated mechanism[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2014, 19(8): 841-845.

参考文献 16

[1]	Rosamond W, Flegal K, Furie K, et al.Heart disease and stroke statistics--2008 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee[J]. Circulation, 2008, 117(4): e25-146.
[2]	Zhao ZQ, Corvera JS, Halkos ME, et al.Inhibition of myocardial injury by ischemic postconditioning during reperfusion: comparison with ischemic preconditioning[J]. Am J Physiol Heart Circ Physiol, 2003, 285(2): H579-588.
[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]	Lee DS, Steinbaugh GE, Quarrie R, et al.Ischemic postconditioning does not provide cardioprotection from long-term ischemic injury in isolated male or female rat hearts[J]. J Surg Res, 2010, 164(2): 175-181.
[5]	Dermietzel R, Gao Y, Scemes E, et al.Connexin43 null mice reveal that astrocytes express multiple connexins[J]. Brain Res Brain Research Rev, 2000, 32(1): 45-56.
[6]	Chew SS, Johnson CS, Green CR, et al.Role of connexin43 in central nervous system injury[J]. Exp Neurol, 2010, 225(2): 250-261.
[7]	张桂青,麻超,骆翔,等. 甘珀酸干预对大鼠脑缺血再灌注损伤的影响[J]. 中国组织化学与细胞化学杂志, 2009, 18(3): 261-265.
[8]	Hosseinzadeh H, Nassiri Asl M, Parvardeh S.The effects of carbenoxolone, a semisynthetic derivative of glycyrrhizinic acid, on peripheral and central ischemia-reperfusion injuries in the skeletal muscle and hippocampus of rats[J]. Phytomedicine, 2005, 12(9): 632-637.
[9]	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.
[10]	韩冬,孙淼,张硕,等. 缺血后处理对大鼠脑缺血再灌注的神经保护作用[J]. 中国医科大学学报, 2012, 41(10): 896-899.
[11]	Cave A, Garlick P.Re: Preconditioning with ischemia: a delay of lethal cell injury in ischemic myocardium[J]. J Mol Cell Cardiol, 2000, 32(9): 1759-1760.
[12]	董淑英,童旭辉,蒋国君,等. 星形胶质细胞中缝隙连接蛋白connexin43的表达及其功能调控[J]. 南方医科大学学报, 2012, 32(10): 1423-1426.
[13]	Tong X, Dong S, Yu M, et al.Role of heteromeric gap junctions in the cytotoxicity of cisplatin[J]. Toxicology, 2013, 310: 53-60.
[14]	Pahujaa M, Anikin M, Goldberg GS.Phosphorylation of connexin43 induced by Src: regulation of gap junctional communication between transformed cells[J]. Exp Cell Res, 2007, 313(20): 4083-4090.
[15]	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): 461-468.
[16]	Naitoh K, Yano T, Miura T, et al.Roles of Cx43-associated protein kinases in suppression of gap junction-mediated chemical coupling by ischemic preconditioning[J]. Am J Physiol Heart Circ Physiol, 2009, 296(2): H396-403.

缝隙连接在缺血后处理保护大鼠脑缺血再灌注损伤中的作用及可能机制

Effect of gap junction in ischemic post-conditioning on cerebral ischemic-reperfusion injury in rats and its associated mechanism

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