Human urinary kallidinogenase suppresses cerebral inflammation in experimental stroke and downregulates nuclear factor-kappaB.
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.
Chen
Zhi-bin
ZB
Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, 321 Zhongshan Road, Nanjing, PR China.
Huang
Dan-qing
DQ
Niu
Feng-nan
FN
Zhang
Xin
X
Li
Er-guang
EG
Xu
Yun
Y
D000818:Animals; D001519:Behavior / Q000502:physiology; D015415:Biomarkers / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003029:Coagulants / Q000627:therapeutic use / Q000652:urine; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D007249:Inflammation / Q000188:drug therapy / Q000473:pathology; D007610:Kallikreins / Q000627:therapeutic use / Q000652:urine; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000627:therapeutic use / Q000652:urine; D009483:Neuropsychological Tests; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D015415:Biomarkers; D003029:Coagulants; D016328:NF-kappa B; D018696:Neuroprotective Agents; D048049:Extracellular Signal-Regulated MAP Kinases; D007610:Kallikreins