Neanthes japonica (Iznka) fibrinolytic enzyme reduced cerebral infarction, cerebral edema and increased antioxidation in rat models of focal cerebral ischemia.
Thrombolytic agent is increasingly being used in treating acute ischemic stroke. A novel protease with strong thrombolytic activity, Neanthes japonica (Iznka) fibrinolytic enzyme (NJF) discovered in our laboratory has been reported with characteristics of direct hydrolyzing fibrin and fibrinogen. The neuroprotective effect of NJF and urokinase (UK) was tested in rat models of middle cerebral artery occlusion (MCAO). The model was successfully produced by introducing an intraluminal suture into the left middle cerebral artery (MCA). NJF (0.25, 0.5, 1mg/kg) was injected intravenously 1h after the onset of reperfusion. Compared with vehicle group, MCAO animals treated with NJF showed dose dependent reduction in cerebral infarction with improved neurological outcome. Meanwhile, ischemia induced cerebral edema was reduced in a dose dependent manner. Treatment with NJF at 0.5mg/kg was almost equivalent to UK at 15,000U/kg dosage in the reduction of cerebral infarction and cerebral edema. Biomedical assay showed that NJF treatment suppressed lipid peroxidation and restored superoxide dismutase (SOD) activities in brain tissue. These results suggest that NJF posses neuroprotective potential in rat MCAO and reperfusion model. Neuroprotection shown by NJF may be attributed to inhibition of lipid peroxidation, increase in endogenous antioxidant defense enzymes.
Department of Biochemistry and Molecular Biology, Norman Bethune College of Medicine, Jilin University, 126 Xinmin Street, Changchun, Jilin Province 130021, China.
Shao-Hua
SH
Wang
Qi
Q
Li
Zhi-Hui
ZH
Deng
Xue
X
Ji
Xi
X
Jiang
Xin
X
Ge
Qi-Qing
QQ
Bo
Jia-Yue
JY
Cui
Lian-Zhi
LZ
Zhang
Jian-Kai
JK
Liu
Min
M
Hong
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D004195:Disease Models, Animal; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010447:Peptide Hydrolases / Q000627:therapeutic use*; D011077:Polychaeta / Q000201:enzymology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology
D000975:Antioxidants; D018696:Neuroprotective Agents; D010447:Peptide Hydrolases