Experimental Study on Protective Effect of Ischemic Preconditioning on Ischemia-Reperfusion Injury

Abstract

Abstract: Objective: Explore the protection of cerebral ischemic preconditioning on ischemia-reperfusion injury by observing the expression changes of TLR4 and TNF-α in cerebral cortex of rats, further investigate its signification. Methods: Thirty six SPF healthy male SD rats were assigned randomly into 3 group: cerebral ischemic preconditioning group (CIP group, n=12), ischemia-reperfusion group (I/R group, n=12),and sham group (Sham group, n=12 ).The I/R group were subjected to 2 hours of right middle cerebral artery occlusion (MCAO) reperfusion with suture-occluded method to establish focal cerebral ischemia reperfusion injury model. 10 miniutes MCAO by suture-occluded was uesd as CIP, 72 hours after reperfusion, given the same treatment like the I/R group. For the Sham group, separate the carotid artery only. One day after surgery, the animals were sacrificed. The infarction volume was evaluated by the method of TTC staining, the neural behavioral score were measured by Zea Longa assessment criteria and the expression levels of TLR4 and TNF-α mRNA were assessed by the method of real-time quantitative PCR. Results: Comparison of rats in 1 d after ischemia, the infarct volume in CIP group was lower than I/R group, the difference was statistically significant (P<0.05). Compared with I/R group, the neural behavioral scores of CIP group were significantly reduced, there exists significant differences(P＜0.05). The mRNA expression of TLR4 and TNF-α in CIP group and I/R group were both apparently higher than the sham group (P＜0.05,P＜0.01), the expression of both in CIP group were significantly lower than the I/R group(P<0.05). Conclusion: Cerebral ischemic preconditioning can ameliorate the dysfunction produced by ischemia-reperfusion injury, and the ischemia reperfusion injury of brain tissue may be alleviated by down regulating the expression of proinflammatory factors, which could alleviate the inflammatory response.

Key words: ischemic preconditioning, ischemia-reperfusion injury, Toll-like receptors 4 (TLR4), tumor necrosis factor-&, alpha, (TNF-&, alpha, )

CLC Number:

R743

ZHANG Jing, ZOU Yu-an, DONG Xiao-hua, MA Fei, WANG Huan-huan. Experimental Study on Protective Effect of Ischemic Preconditioning on Ischemia-Reperfusion Injury[J]. ACTA NEUROPHARMACOLOGICA, 2015, 5(6): 1-5.

References

[1]Vijayakumar N Thushara, Amit Sangwan, Bhargy Sharma, et al. Cerebral ischemic preconditioning: the road so far....[J]. Mol neurobiol, 2016, 53(4): 2579-2593.

[2]Gary H Danton, W Dalton Dietrich. Inflammatory mechanisms after ischemia and stroke[J]. J Neuropathol Exp Neurol, 2003, 62(2): 127-136.

[3]Matthew K Tobin, Jacqueline A Bonds, Richard D Minshall, et al. Neurogenesis and inflammation after ischemic stroke: what is known and where we go from here[J]. J Cereb Blood Flow Metab, 2014, 34(10): 1573-1584.

[4]Jesus M Pradillo, David Fernández-López, Isaac García-Yébenes, et al. Toll-like receptor 4 is involved in neuroprotection afforded by ischemic preconditioning[J]. J Neurochemistry, 2009, 109(1): 287-294.

[5]Fran Balkwill, Christian Joffroy. TNF: a tumor-suppressing factor or a tumor-promoting factor?[J]. Future Oncology, 2010, 6(12): 1833-1836.

[6]郝玉曼，罗祖明，周东. 局灶预缺血诱导脑缺血耐受的动物模型［J］.中风与神经疾病杂志, 2003, 20(2): 129 -130．

[7]Longa E Z Weinstein P R, Carlson S, et al. Reversible middle cerebral artery occlusion without craniectomy in rats[J]. Stroke, 1989, 20(1): 84-91.

[8]Kenneth J Livak, Thomas D Schmittgen. Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method[J]. Methods, 2001, 25(4): 402-408.

[9]Olga V Sirotkina, A B Laskovets, Vitaly Goldobin, et al. The molecular mechanisms of platelets activation in patients with cerebrovascular disease[J]. Biomed Khim, 2015, 61(5): 606-612.

[10]Grant C Sorkin, Travis M Dumont, Maxim Mokin M, et al. Hyperacute carotid stent thrombosis during emergent revascularization treated with intraarterial eptifibatide after systemic administration of recombinant tissue plasminogen activator[J]. J Vasc Interv Neurol, 2015, 8(3): 50-55.

[11]Sorkin GC, Dumont TM, Mokin M,et al. Hyperacute Carotid Stent Thrombosis During Emergent Revascularization Treated with Intraarterial Eptifibatide After Systemic Administration of Recombinant Tissue Plasminogen Activator[J]. J Vasc Interv Neurol,2015,8(3):50-55.

[12]Kate N Murray, Sylvie Girard, William Holmes, et al. Systemic inflammation impairs tissue reperfusion through endothelin-dependent mechanisms in cerebral ischemia[J]. Stroke, 2014, 45(11): 3412-3419.

[13]Lan Lan, Tao Jing, Azhen Chen, et al. Electroacupuncture exerts anti-inflammatory effects in cerebral ischemia-reperfusion injured rats via suppression of the TLR4/NF-κB pathway[J]. Int J Mol Med, 2013, 31(1): 75-80.

[14] Natalie Lovland Halladin. Oxidative and inflammatory biomakers of ischemia and reperfusion injuries[J]. Dan Med J, 2015, 62(4): B5054.

[15]Wang Hong-xin, Zhang Kan, Zhao Lan, et al. Anti-inflammatory effects of vinpocetine on the functional expression of nuclear factor-kappa B and tumor necrosis factor-alpha in a rat model of cerebral ischemia-reperfusion injury[J]. Neurosci Lett, 2014, 566: 247-251.