Screening Of 18 F-FDG Micro PET/CT In Rat Model Of Cerebral Ischemia-reperfusion Injury And Evaluation Of The Efficacy Of Panax Notoginseng Saponins

Part 1The application of ¹⁸F-FDG micro PET in cerebral ischemia reperfusion model screeningObjective: We take pathological result as gold criteria of cerebral ischemia,investigating the practicability of ¹⁸F-FDG micro PET/CT in screening the cerebral ishchemia model.Methods: 18 male SD rats were randomly selected and numbered,the cerebral ischemia reperfusion model was made by using the suture method of reversible middle cerebral artery embolism.We create inclusion criteria of the rats:the Zea-Longa score is between 1 and 4 When postoperative awake.2 and 24 hours after operation,Garcia 18 points method was used to evaluate neurological functions of rats.In2 and 24 hours after operation,¹⁸F-FDG was injected in to caudal vein after anesthesia;micro PET/CT scan was conducted at 40 min after radiotracer injection.Visual and semiquantitative analysis were adopted to analyze the images.The rats that was accidental dead were performed autopsy and HE staining;the rats that were still alive at 24 hours after operation,the brain tissue was taken out quickly after the scan,The infarction rates were calculated by TTC staining.Results: 18 selected rats' pathological findings: 11 rats were the MCAO/R model,4 were subarachnoid hemorrhage,3were subarachnoid hemorrhage and cerebral hemorrhage.8-12 h after operation,4 rats died accidentally.2h after operation,the accuracy rate of neurological function score and micro PET/CT were 61.1%?11/18?and 83.3%?15/18?respectively,the difference was statistically significant?P=0.043<0.05?;24hours after operation,the accuracy rate of neurological function score and micro PET/CT were 78.6%?11/14?,100%?14/14?,no statistical difference?P>0.05?.Conclusions: Micro PET/CT is better than the nerve function score in screening cerebral ischemia reperfusion model in early stage;24h after operation,the two were not statistically different.Part 2Effect of panax notoginceng saponins on brain glucose metabolism in rat with cerebral ischemia reperfusion injury observed by¹⁸F-FDG micro PET/CTObjective:The dynamic changes of brain glucose metabolism after ischemia reperfusion injury was observed by micro PET/CT,which was combined with neurological deficit scores,pathological and immunohistochemi cal results.To evaluate the therapeutic effect of panax notoginseng sapinis?PNS?in cerebral ischemia reperfusion injury and primarily discussed the mechanism of how PNS affects the brain glucose metabolism.Methods:40 heathy adult male rats were randomly divided into five groups?n=8?:sham group?group A?,blank control group?group B?,low dose PNS treatment group?group C?,high dose PNS treatment group?group D?and Positive control group?group E?.According to the improved method of Zea-longa,intraluminal thread was inserted through right external carotid arterty,to make right middle cerebral artery occlusion.In control group?group B?and treatment groups?group C?D?E?,the insertion depth of intraluminal thread was 1.8cm;in sham group,the depth was 1.0 cm.Reperfusion was performed by withdrawing it after one hour of MCAO.The treatmens of the Low dose PNS treatment group?group C?,high dose PNS treatment group?group D?and Positive control group?group E?were started at 3 hours afer operation,last for 3 days.The rats in group C?D and Ereceived intraperitoneal drug therapy,the drugs and dosage in group C?D and E are low dose PNS?57.5mg/kg?,high dose PNS?115mg/kg?and edaravone?4mg/kg?respectively.In sham group?group A?and blank control group?group B?,rats received intraperitoneal injection of the same volume of normal saline.Each rat was injected ¹⁸F-FDG into caudal vein at 2h?6h?24h?48h and 72 h after successful modeling,40 minutes after injection,micro PET/CT was conducted.Meanwhile,Garcia neurological function evaluation was performed.Micro PET/CT image was analyzed by visual analysis and semi quantitative analysis.Then making the perfusion of brain,taking out of the brain after 72 hours,HE stained were performed,GLUT-1 and GLUT-3 were detected by immunohistochemistry.Repeated measures was used to analyze the data,P<0.05 was statistically significant.Results:1.Neurological function score :?1?There was no significant difference at different time points in sham group?F=1.699,P=0.178>0.05?;?2?As time went by,Each group's neurological function recovered to different extent,and a statistically significant differences?P<0.05??3?The effects of neural function recovery:Positive control group=high dose PNS treatment group>low dose PNS treatment group> blank control group.2.Micro PET/CT can directly reflect the glucose metabolism of ischemic and peripheral edema brain tissue,it's glucose metabolism was significantly decreased.3.micro PET/CT :?1?In sham group,There was no significant difference in SUV at each time point?F=1.912,P=0.273>0.05?.?2?There were differences in each time point in the group B?C?D and E,thedifference was significant?P<0.05?.The SUV reached minimum at 6h in each group?SUV =1.08±0.18,n=32?,starting to increase at the next time point.?3?There was no significant difference among group B?C?D and E,before the drug intervention,2h after operation?P>0.05?.?4?Effects of drug intervention on brain glucose metabolism:Positive control group = high dose PNS group>low dose PNS group> blank control group.4.HE staining can directly reflect the edema degree of the treatment group?C?D?E?was significantly lower than that of the control group,the edema degree in the high dose group was lower than that in the low dose treatment group.5.Immunohistochemistry can directly reflect that the number of the positive expression cells of GLUT-1 and GLUT-3in the treatment group?C?D?E group?was more than that in the control group.the positive expression cell of the high dose treatment group was more than that of the low-dose treatment group.Conclusion:1.micro PET/CT clearly showed the approximate range and the change of glucose metabolism in cerebral ischemia and peripheral edema brain tissue.2.Panax notoginseng saponins have neuroprotective effects,it can improve the neurological impairm ent symptoms,alleviate cerebral edema,increase positive expression of GLUT-1 and GLUT-3 and increase glucose metabolism in ischemic and peripheral brain tissue.