Limb remote ischemic postcondtioning promoting the expression of  heat shock protein 70 in the rat cortex after focal cerebral ischemia reperfusion injury

ZHOU Fang-fang LI Shuai QI Wen-qian ZONG Yong-hua ZHANG Ming-xiao YANG Hui-jun HU Xiao-song*

Acta Anatomica Sinica ›› 2015 ›› Issue (3) : 310-316.

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Acta Anatomica Sinica ›› 2015 ›› Issue (3) : 310-316. DOI: 10.16098/j.issn.0529-1356.2015.03.004

Limb remote ischemic postcondtioning promoting the expression of  heat shock protein 70 in the rat cortex after focal cerebral ischemia reperfusion injury

  • ZHOU Fang-fang1 LI Shuai2 QI Wen-qian1 ZONG Yong-hua1 ZHANG Ming-xiao1 YANG Hui-jun2 HU Xiao-song 2*
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Abstract

Objective To explore the underlying molecular mechanisms of limb remote ischemic postconditioning (LRIP) protective role in the brain by observing the localization and changes of positive cells expression of heat shock protein 70 (HSP70) in focal cerebral ischemia-reperfusion injury (I/R) of rat cortical infarct areas after remote ischemic postcondtioning treatment. Methods A SD rat model of focal cerebral ischemia reperfusion was induced by intraluminal 1 hour transient middle cerebral artery occlusion with a nylon monofilament suture.Ischemic animals were randomly assigned to 3 groups: sham group, I/R group and LRIP group, 5 animals each group.The LRIP performed immediately after reperfusion(LRIP was generated by 3 cycles of 10 minutes occlusion/10 minutes release of the bilateral hind femoral artery used rubber band). To determine whether the model of MCAO was successful, Zea longa score method was used. Rats were sacrificed on 1day or 3days after reperfusion and the brain was obtained by decapitation. Rats were evaluated for neurological deficits just before sacrifice by Garcia. Brains were harvested for infarct size estimation used 2, 3,5-triphenyl tetrazolium chloride(TTC). Western blotting was used to analyze the quantitative alterations of HSP70.Immunohistochemistry and double immunofluorescence histochemistry were used to observe the distribution, type and number of positive cells of HSP70. Results Compared with I/R group, LRIP treatment significantly improved neurological functions(P<0.05)and decreased infract size(P<0.05)as well as upregulated HSP70 expression. There was no statistically significant difference between LRIP and I/R group at 1day (P>0.05)except for that of 3days(P<0.01). HSP70 was localized predominantly in neurons and endothelia cells and astrocytes in ischemic peripheral areas. Conclusion LRIP treatment could improve neurological functions as well as decrease infract size. According to the results, we speculate this protective effect likely by increasing the neurons, endothelia cells and astrocytes expression of HSP70 in ischemic peripheral areas.

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ZHOU Fang-fang LI Shuai QI Wen-qian ZONG Yong-hua ZHANG Ming-xiao YANG Hui-jun HU Xiao-song*. Limb remote ischemic postcondtioning promoting the expression of  heat shock protein 70 in the rat cortex after focal cerebral ischemia reperfusion injury[J]. Acta Anatomica Sinica. 2015(3): 310-316 https://doi.org/10.16098/j.issn.0529-1356.2015.03.004

References

[1]Zhao H. The protective effect of ischemic postconditioning against ischemic injury: from the heart to the brain [J].J Neuroimmune Pharmacol,2007, 2(4): 313-318. 
[2]Liu Q, Zhou S, Wang Y, et al. A feasible strategy for focal cerebral ischemia-reperfusion injury: remote ischemic postconditioning [J]. Neural Regen Res, 2014, 9(15):1460-1463. 
[3]Zhao H, Ren C, Chen X, et al. From rapid to delayed and remote postconditioning: the evolving concept of ischemic postconditioning in brain ischemia [J]. Curr Drug Targets, 2012, 13(2):173-187. 
[4]Ma Y, Lu C, Li C, et al. Overexpression of HSPA12B protects against cerebral ischemia/reperfusion injury via a P13K/Akt-dependent mechanism [J]. Biochim Biophys Acta, 2013, 1832(1):57-66.
[5]Zheng Z, Kim JY, Ma H, et al. Anti-inflammatory effects of the 70 kDa heat shock protein in experimental stroke [J]. Cereb Blood Flow Metab, 2008, 28(1):53-63. 
[6]Xu L, Emery JF, Ouyang YB, et al. Astrocyte targeted overexpression of Hsp72 or SOD2 reduces neuronal vulnerability to forebrain ischemia [J]. Glia, 2010, 58(9):1042-1049.
[7]Hu XS, Zhou D, Tang Y, et al. Expression of laminin and matrix metalloproteinase-9 around the infarct area hollowing focal ischemia in rat brains and its significance [J]. West China Medical Journal, 2013,28(5):651-654. (in Chinese)
胡晓松,周东,唐瑜,等.层黏连蛋白及基质金属蛋白酶-9在大鼠局灶性脑缺血梗死区周围的表达及意义[J].华西医学,2013, 28(5): 651-654.
[8]Garcia JH, Wagner S, Liu KF, et al. Neurological deficit and extent of neuronal necrosis attributable to middle cerebral artery occlusion in rats[J]. Stroke, 1995, 26(4):627-634. 
[9]Longa EZ,Weinstein PR,Calson S,et al. Reversible middle cerebral artery occlusion without craniectomy in rats [J]. Stroke,1989,20(1):84-91.
[10]Joshi CN, Jain SK, Murthy PS, et al. An optimized triphenyltetrazolium choride method for identification of cerebral infarcts [J].Brain Res Brian Res Protoc, 2004, 3(1):11-17.
[11]Lin TN, He YY, Wu G. Effect of brain edema on infarct volume in a focal cerebral ischemia model in rats [J]. Stroke, 1993, 24(1):117-121.
[12]Ren C, Gao M, Dornbos D 3rd, et al. Remote ischemic post-conditioning reduced brain damage in experimental ischemia/reperfusion injury [J]. Neurol Res, 2011, 33(5):514-519. 
[13]Lim SY, Hausenloy DJ. Remote ischemic conditioning: from bench to bedside [J]. Front physiol, 2012, 3:27. 
[14]Basu S, Binder RJ, Suto R, et al. Necrotic but not apoptotic cell death releases heat shock proteins, which deliver a partial maturation signal to dendritic cells and activate the NF-kappa B pathway[J]. Int Immunol,2000, 12(11):1539-1546.
[15]Srivastava P. Roles of heat-shock proteins ininnate and adaptive immunity [J]. Nat Rev Immunol, 2002, 2(3): 185-194. 
[16]Guo YL, Gao YM. The time relationships between apoptosis of neuron and endotheliocyte with the expression of Bcl-2 and Bax after focal cerebral ischemia reperfusion in rats [J]. Acta Anatomica Sinica, 2002,33(2):152-156. (in Chinese)
郭云良,高英茂.脑缺血再灌注后神经元和内皮细胞凋亡与Bcl-2和Bax表达的时相关系[J].解剖学报,2002,33(2):152-156.
[17]Zheng GY, Chen XCh, Liu ChY, et al. The activation of SAPK/JNK and p38MAPK may be the possible mechanism of neuronal apoptosis induced by no after cerebral ischemia-reperfusion [J]. Acta Anatomica Sinica, 2006,37(6):633-639. (in Chinese)
郑关毅, 陈晓春, 刘昌云, 等. 一氧化氮激活应激活化蛋白激酶/c-Jun氨基末端激酶及p38MAP激酶诱导脑缺血再灌注后神经元凋亡 [J]. 解剖学报, 2006,37(6):633-639.
[18]Goel G, Guo M, Ding J, et al. Combined effect of tumor necrosis factor (TNF)-α and heat shock protein (HSP)-70 in reducing apoptotic injury in hypoxia: a cell culture study[J]. Neurosci Lett, 2010, 483(3):162-166. 
[19]Lee MY, Kim SY, Shin SL, et al. Reactive astrocytes express bis, a bcl-2-binding protein, after transient forebrain ischemia [J]. Exp Neurol, 2002, 175(2):338-346. 
[20]Kato H, Kogure K, Liu XH, et al. Immunohistochemical localization of the low molecular weight stress protein HSP27 following focal cerebral ischemia in rat[J].Brain Res,1995,679(1):1-7.

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