The Effects Of Mailuoning Injection On Cerebral Ischemia-reperfusion Injury

Background Nowadays, the cerebrovascular disease has become the second largest cause of death in our country. Its higher disability and death rate brings heavy burden to patients,families and society。Cerebral ischemic-reperfusion injury is an important pathological mechanism in the process of ischemia.It has been the focus of the study abroad and home. Mailuoning injection has been widely used in clinical. Although its efficacy on ischemic cerebrovascular diseases has been preliminarily confirmed, the best administrated dosege and time have not been reported so far.Meanwhile,it's specific mechanisms against ischemic brain injury have not been described in detail because of its complex composition.This experiment interfered cerebral ischemia–reperfusion rat models with mailuoning injection and observed its treatment effects from the neurological scores, ultrastructure, regional cerebral blood flow, apoptotic cells and VEGF. Thus to explore the more appropriate administration dosage and time and the possible molecular mechanisms in experimental animals.Methods 1.Cerebral ischemia-reperfusion models of SD rats were made with modified Longa methed. 2. Different doses of mailuoning injection (20,40,80mg·Kg-1·d-1)were used to interfere rat models. Neurological scores(modified Bederson methed) , apoptotic cells in hippocampus(flow cytometry) ,regional cerebral blood flow(laser doppler flowmetry) were dtected to investigate the appropriate administration dosage.3. The appropriate administration dosage of mailuoning injection was used at different time points(6,24,48h,7d). Neurological scores(modified Bederson methed), ultrastructure of hippocampus CA1 neurons (electronmicroscopy) were evaduated to explore the appropriate administration time.Meanwhile,the VEGF,Caspase-3 positive cells were counted by immunohistochemistry to explore the possible mechanism.Results 1.The neurological scores, apoptotic cells and blood flow of the higher doses (≥40mg·Kg-1·d-1) groups were statistically different with the low dose (20mg·Kg-1·d-1) group(P <0.05 or 0.01).2. The neurological scores of rats in treatment groups was abviously lower compared with the ischemia-reperfusion group.Compared with 7d group, the neurological scores of the treatment groups administrated within 48h were statistically different(P <0.0 or <0.01).The earlier the administration, the more significant the recovery of hippocampal neurons ultrastructure.3. VEGF positive cells in brain tissue of treatment groups were significantly increased than that of the ischemia-reperfusion group (non-treatment group) (P <0.05 or 0.01) and the Caspase-3 positive cells were decreased(P <0.05).Conclusion 1.Mailuoning injection has a treatment effect on cerebral ischemia-reperfusion injury. It can inhibit neuronal apoptosis, increase regional cerebral blood flow and reduce neurological scores.The effects of middle and high administration dosages are better.2.The treatment effects are better when administrated within 48h. The structure of hippocampal CA1 neurons can restore better when administrated earlier and can reduce the neurological scores.Mailuoning injection could play the treatment role by increasing VEGF levels and decreasing Caspase-3 levels.