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Oxidative Medicine and Cellular Longevity
Volume 2016 (2016), Article ID 1843201, 14 pages
Research Article

Tissue Kallikrein Alleviates Cerebral Ischemia-Reperfusion Injury by Activating the B2R-ERK1/2-CREB-Bcl-2 Signaling Pathway in Diabetic Rats

1Department of Neurology, Jinling Hospital, Medical School of Nanjing University, Nanjing, Jiangsu 210002, China
2Department of Neurology, Maanshan Municipal People’s Hospital, Maanshan, Anhui 243000, China
3Department of Neurology, Jinling Hospital, Southern Medical University, Nanjing, Jiangsu 210002, China
4Department of Orthopedics, Maanshan Municipal People’s Hospital, Maanshan, Anhui 243000, China
5State Key Laboratory of Organ Failure Research, National Clinical Research Center for Kidney Disease, Department of Biostatistics, School of Public Health and Tropical Medicine, Southern Medical University, 510515 Guangzhou, China

Received 23 February 2016; Accepted 6 June 2016

Academic Editor: Angel Catalá

Copyright © 2016 Ruifeng Shi et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Diabetes mellitus (DM) substantially increases the risk of ischemic stroke and reduces the tolerance to ischemic insults. Tissue kallikrein (TK) has been demonstrated to protect neurons from ischemia/reperfusion (I/R) injury in orthoglycemic model by activating the bradykinin B2 receptor (B2R). Considering the differential effects of B2R or bradykinin B1 receptor (B1R) on cardioprotection and neuroprotection in I/R with or without diabetes, this study was designed to investigate the role of TK during cerebral I/R injury in streptozotocin-induced diabetic rats. Intravenous injection of TK inhibited apoptosis in neurons, alleviated edema and inflammatory reactions after focal cerebral I/R, significantly reduced the infarct volume, and improved functional recovery. These beneficial effects were accompanied by activation of the extracellular signal-regulated kinase 1/2 (ERK1/2), cAMP response element-binding (CREB), and Bcl-2 signal proteins. Inhibition of the B2R or ERK1/2 pathway abated the effects of TK, whereas an antagonist of B1R enhanced the effects. These findings reveal that the neuroprotective effect of TK against cerebral I/R injury in streptozotocin-induced diabetic rats mainly involves the enhancement of B2R and ERK1/2-CREB-Bcl-2 signaling pathway activity.