Influences Of Lycopene On Blood-brain Barrier And Nerve Damage In Rats With Cerebral Small Vessel Disease By Regulating JAK2/STAT3/VEGF Signaling Pathway

Cerebral small vessel disease（CSVD）is a comprehensive syndrome of a series of clinical,imaging and pathological manifestations caused by various causes acting on arterioles,arterioles,capillaries,venules and venules in the brain.The pathogenesis of CSVD is very complex.Oxidative stress,brain tissue ischemia,vascular endothelial dysfunction,blood-brain barrier rupture,neuroinflammatory reaction,venous collagen disease and other mechanisms play an important role in the occurrence and development process.Therefore,anti-inflammation and anti-oxidation drugs can slow down the speed of blood-brain barrier and nerve injury in patients with cerebrovascular disease,and alleviate the clinical symptoms of patients;Studies have shown that JAK2/STAT3/VEGF signal pathway is an antioxidant stress pathway,which has protective effects on oxidative stress injury.Lycopene has extremely strong antioxidant and free radical scavenging effects.It is a natural carotene.Therefore,this experiment aims to study whether lycopene can reduce the permeability of blood-brain barrier in rats with cerebrovascular disease through JAK2/STAT3/VEGF pathway,and has a protective effect on neurons.Fifty CSVD rat models were prepared by in vitro injection of the same germline microemboli and were randomly grouped into model group,low-dose lycopene(65 mg·kg^-1)group,high-dose lycopene(85 mg·kg^-1)group,AG490(JAK2 inhibitor,3.5mg·kg^-1)group,and high-dose lycopene(85mg·kg^-1)+AG490(3.5mg·kg^-1)group,10 in each group,another 10 SD rats were regarded as the sham operation group.After grouping with lycopene and AG490,the cognitive ability of rats was detected by Morris water maze test and dark avoidance test;the permeability of blood-brain barrier in rats was detected by Evans blue method;the number of rat hippocampal neurons was detected by Nissl staining;the levels of inflammatory factors prostaglandin E2（PGE2）,tumor necrosis factor-α（TNF-α）,and oxidative stress factors catalase（CAT）,superoxide dismutase（SOD）,Malondialdehyde（MDA）in rat brain tissue were detected by ELASA method and colorimetric method;the expressions of matrix metalloproteinase（MMP）2,MMP9,tight junction-related proteins（ZO-1,Occludin）and JAK2/STAT3/VEGF pathway-related proteins in rat brain were detected by western blotting.The study found that compared with the sham operation group,the times of rats crossing the platform,the time of staying in the target quadrant,step through latency,the number of hippocampal neurons,the levels of CAT and SOD in brain tissue,the protein expressions of ZO-1,Occludin and VEGF,and the p-JAK2/JAK2,p-STAT3/STAT3 were obviously decreased in the model group（P<0.05）,and the error times,Evans blue content,levels of brain tissue PGE2,TNF-αand MDA,and the protein expressions of MMP2 and MMP9 were obviously increased（P<0.05）.Compared with the model group,the times of rats crossing the platform,the time of staying in the target quadrant,step through latency,the number of hippocampal neurons,the levels of CAT and SOD in brain tissue,the protein expressions of ZO-1,Occludin and VEGF,and the p-JAK2/JAK2,p-STAT3/STAT3 were all increased in the low-dose lycopene group and the high-dose lycopene group（P<0.05）,and the error times,Evans blue content,levels of brain tissue PGE2,TNF-αand MDA,and the protein expressions of MMP2 and MMP9 were all decreased（P<0.05）,high dose lycopene is more effective;the change trend of each index in AG490 group was opposite to that in lycopene groups,and AG490 could reverse the effect of lycopene.Therefore,Lycopene can inhibit inflammation and oxidative stress in CSVD rats by activating JAK2/STAT3/VEGF signaling,thereby reducing the blood-brain barrier and nerve damage,and improving their cognitive ability.