| ObjectiveZG freeze-dried powder is a composition drug triturated under the guidance of TCM theory by our team which mainly contains catalpol and puerarin for the treatment of ischemic cerebrovascular disease. Puerarin is used for cerebral infarction clinically as a vasodilator drugs. Catalpol is reported to play a neuroprotective and vascular remodeling role in the treatment of stroke. This is the first time to combine the two drugs to determine whether the combination could be a treatment of cerebral ischemia and cerebral edema.Methods1. Optimal proportion of catalpol and puerarin is designed using Doehlert matrix (DM). Bleeding time, clotting time, survival time of sodium nitrite poisoning and MDA, SOD activity of acute ischemia brain tissue were measured after given intravenous injection of the designed doses of DM for 7 d. Results were optimized by response surface method for optimal proportion.2. To verify the reasonableness of ZG compatibility,60 pMCAO rats were divided into 6 groups randomly:sham-operated, model, edaravone (3 mg/kg). puerarin (A2 mg/kg), catalpol (B2 mg/kg), and ZG (A2B2 mg/kg) respectively. Behavioral testing and TTC staining were carried out after administration for 7 days. Infarction area was analyzed by biomedical image analysis system. 3. To execute the regularity of brain edema and behavioral testing,ischemia rats were divided to 8-time groups:3h,6h,12h,24 h,48 h,72 h,5 d,7 d respectively At each time point animals were sacrificed after evaluation of behavioral tests to determine brain water content.4. Treatment of brain edema with ZG compatibility was detected. pMCAO rats were divided into 6 groups:sham-operated, model, edaravone (3 mg/kg), ZG (0.5 X A2B2 mg/kg), ZG(A2B2 mg/kg), ZG (2 X A2B2 mg/kg). Brain water content was determined by dry-wet weight method as following formula:(wet weight-dry weight)/ wet weight×100%.Results1. Optimal proportion results of catalpol and puerarin suggested that intravenous injection of puerarin dose of A mg/kg and catalpol dose of B mg/kg was the best combination.2. Longa score and beam walking score results show that the model group showed significant neurological behavior disorder (P<0.01). Administration of catalpol, puerarin and ZG compatibility could significantly ameliorate the animal's behavior disorders (P<0.05, P<0.01). Brain infarction of model group significantly increased compared with normal rats, while the treated group could significantly reduce infarct volume (P<0.05, P<0.01).3. Behavior disorders and brain water content began to increase after 12 h. Edema peaked at 24 h-48 h while neurological impairment consistent with the performance of its peak almost 72 h, decreased from 72 h and recovered to normal at 7 d.4. ZG group rats can significantly reduce the brain water content of model rats (P<0.05, P<0.01). Brain edema of A2B2 group returned to normal level.Conclusion1. This study confirmed that ZG compatibility could treat ischemic damage effectively. The combination of puerarin A mg/kg and catalpol B mg/kg (mice intravenous injection dose) educed the best treatment, and the compatibility of the two drugs was better than either singly used but the difference was not significant. 2. Brain edema appeared at 12 h after cerebral infarction with severe behavioral disorders and increased brain water content. ZG compatibility rats significantly reduced brain water content of ischemic rats. The brain water content of A2B2 group fell to normal level.
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