Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, PR China.
J Cereb Blood Flow Metab. 2010 Jul;30(7):1356-65. doi: 10.1038/jcbfm.2010.19. Epub 2010 Feb 24.
The purpose of this study is to investigate the possible mechanism and the neuroprotective effect of human urinary kallidinogenase (HUK) in cerebral ischemia. The mouse middle cerebral artery occlusion (MCAO) model was used. Mice were treated with HUK (20 PNAU/g per day, intravenous) or saline as control, from the beginning of reperfusion to 72 h. Neurological deficits, infarct size, and BWC were measured at 6, 24, 48, and 72 h after MCAO, respectively. Pathological changes of brain were observed by TUNEL assay. Inflammatory factors were measured by real-time PCR and western blotting. Activation of MAPKs, Akt, and nuclear factor-kappaB (NF-kappaB) was detected by western blotting. Our results indicated that HUK significantly improved neurofunction, decreased infarct size, and suppressed edema, as well as inflammatory mediators as compared with the vehicle group. Furthermore, HUK inhibited the NF-kappaB pathway and activated the MAPK/ERK pathway in this neuroprotection.
本研究旨在探讨人尿激肽原酶（HUK）在脑缺血中的可能作用机制和神经保护作用。采用小鼠大脑中动脉闭塞（MCAO）模型。小鼠从再灌注开始至 72 h 每天接受 HUK（20 PNAU/g，静脉注射）或生理盐水治疗作为对照。分别于 MCAO 后 6、24、48 和 72 h 测量神经功能缺损、梗死面积和脑水含量。TUNEL 法观察脑病理变化。实时 PCR 和 Western blot 法测定炎性因子。Western blot 法检测 MAPKs、Akt 和核因子-κB（NF-κB）的激活。结果表明，与载体组相比，HUK 显著改善了神经功能，减少了梗死面积和脑水肿，抑制了炎症介质。此外，HUK 在这种神经保护作用中抑制了 NF-κB 途径并激活了 MAPK/ERK 途径。
