The Protective Effect Of Curcumin Analogue Cur20 On Animal Models Of Vascular Dementia

Objective: To investigate the protective effect and mechanism of curcumin analogue Cur20 on mice model of vascular dementia.Methods:(1)Mice were randomly divided into sham group(Sham),vascular dementia animal model group(Model),curcumin group(Curcumin)and curcumin analog group(Cur20).The animal model of vascular dementia was prepared by permanent ligation of the right common carotid artery.After 24 hours of surgery,the Curcumin group and the Cur20 group were given the corresponding drug to treatment,while the model and the sham operation group were given the corresponding solvents.On the 14 th day after operation,the mice were subjected to water maze test to test the difference of spatial learning and memory ability of each group mice.On the 19 th day after operation,the mice were subjected to Y-maze test to test the difference of working memory ability of each group.On the 20 th day after operation,the mice were sacrificed.The morphological changes of the hippocampus were observed by Nissl staining.The content of oxidative stress related factors ROS,MDA,GSH and SOD in brain was detected by brain homogenate.The expression of VEGF,CD34,Ang-2,TFEB and HIF-1? related to angiogenesis was detected.(2)Prepare and culture Primary rBMECs;The cell viability of rBMECs with different concentrations Cur20 was detected by MTT;hypoxia chamber to construct Oxygen and glucose deprivation(OGD)to establish cerebral ischemia in vitro,Then observe the morphological changes of rBMECs in different group.MTT assay was used to detect the protective effects of NAC and different concentrations of Cur20 on rBMECs in ischemia model.Flow cytometry was used to detect apoptosis of rBMECs with NAC and different concentrations of Cur20 in ischemia model.ROS content in different groups were detected by high content;The expression of Ki67 in different groups were detected by immunofluorescence;Western Blot detecte the expression of HIF-1?,TFEB and VEGF.Results:(1)Compared with the sham operation group,the escape group latency of the model group was prolonged,the number of crossing the platform was reduced,and the spontaneous alternation rate was significantly reduced,indicating successful modeling.The escape latency of the mice treated with curcumin and Cur20 was significantly shorter than that of the model group,the number of crossing platforms was also significantly increased,and the spontaneous alternation rate was significantly increased,and the number of platform crossings in the Cur20 group was significantly higher than that in the curcumin group.In the model group,the number of neurons in the hippocampus of the mice was decreased,the nucleus was pyknosis,and the damage was obvious.Curcumin and Cur20 could improve the injury.The right common carotid artery ligation can significantly increase the content of ROS and MDA in the brain tissue of mice,and decrease the content of SOD and GSH.The curcumin group and Cur20 can significantly reverse the changes of above indicators.Compared with the model group,the levels of VEGF,CD34,TFEB and HIF-1? in the brain of Cur20 group were increased.The expression level of Ang-2 protein was comparable to that of the model group,and there was no significant difference.Compared with the model,the level of CD34 and TFEB protein in the brain tissue of the curcumin group was significantly increased,while the levels of VEGF,HIF-1? and Ang-2 protein were not significantly different from those in the model group.(2)The cell viability of rBMCEs treated with ischemia model was significantly decreased.The cell viability of rBMCEs pretreated with NAC and Cur20(0.1?M,1?M,10?M)for 2h was improved.Cur20(0.1?M,1?M,10?M)could decrease the apoptosis and ROS content induced by ischemia model,and improve the damaged cell morphology promoted cell proliferation;Cur20 up-regulat the expression of HIF-1?,TFEB,NF-?B and VEGF induced by ischemia model.Conclusion:(1)Cur20 has a protective effect on the ischemic animal model.It mainly reduces the content of ROS and MDA,increases the SOD and GSH content,and exerts antioxidant activity,and reduces the oxidative damage caused by ischemia and hypoxia.Cur20 up-regulat the expression of angiogenesis-related factors VEGF,CD34,HIF-1? and TFEB promote angiogenesis in the ischemic area to enhance the blood supply in the ischemic area.(2)Cur20 has protective effects on rBMECs in oxygen glucose deprivation model.The mechanism may be related to the up-regulated expression of HIF-1?,VEGF and TFEB.