Effect Of Danhong Injection On A Rat Model Of Cerebral Ischemic-Reperfusion Injury And Its Therapeutic Mechanism

Objective:To investigate the effect of Danhong injection(DHI)on a rat model of cerebral ischemic-reperfusion injury with using positron emission tomography,and explore its potential therapeutic mechanism.Method:Rats were performed operation to establish middle cerebral artery occlusion(MCAO)model,and they were divided into 5 groups;sham group,ischemia-reperfusion untreated(IRU)group,DHI-1 group(DHI 1ml/kg/d),DHI-2 group(DHI 2ml/kg/d),and DHI-4 group(DHI 4ml/kg/d).All the treated-groups were intraperitoneally injected with DHI daily for 14 days.The therapeutic effects in terms of cerebral infarct volume,neurological function,and cerebral glucose metabolism were evaluated.Expression of TNF-α and IL-1 β were detected with enzyme-linked immunosorbent assay(ELISA).Levels of mature neuronal marker(NeuN),glial marker(GFAP),vascular density factor(vWF),and glucose transporter 1(GLUT1)were assessed by immunohistochemistry.Results:(1)Compared with the IRU group,the neurological deficit score of DHI treatment groups were significantly higher,especially DHI-2 group and DHI-4 group(P<0.01).Meanwhile,the infarct volume of DHI treatment groups were significantly smaller than that of the IRU group(P<0.01).(2)Compared with the IRU group,the expression of TNF-a in DHI treatment groups significantly decreased(P<0.01).DHI-2 group and DHI-4 group had significantly lower expression of TNF-a and IL-1β than the IRU group(P<0.05).(3)FDG-PET could detect the cerebral glouse metabolism to understand the change of neurological function of brain.Compared with the IRU group,the glouse metabolism of peri-infarct area in DHI treatment groups were significantly increased,espically in DHI-2 group and DHI-4 group 7d and 14d after MCAO(P<0.01).(4)Levels of NeuN,GFAP,vvWF,and GLUT1 were assessed by immunohistochemistry to explore the effect of DHI on neurogenesis,the astrocyte activity,angiogenesis and recovery of glouse metabolism after cerebral ischemia.The numbers of NeuN-positive and Vwf-postive cells in DHI-2 group and DHI-4 group were significantly higher than that of the IRU group(P<0.05).In the DHI-2 and DHI-4 treated animals,the integrated optical density(IOD)of GFAPs was significantly higher than that in the IRU group(P<0.01).Meanwhile,the IOD of GLUT1s in the DHI treatment groups markedly decreased in comparison with the IRU group(P<0.05).Conclusion:Firstly,Danhong injection promotes the recovery of glouse metabolism,reduction of infarct volume and neurological functional recovery after cerebral ishchemia.Secondly,there are neuroprotective effects of DHI in a rat model of cerebral ischemic-reperfusion injury,which related to anti-inflamation,microvascular remodeling,nerve cell regeneration,astrocyte activation and the recovery of glucose utilization.