Effect of lycopene on blood-brain barrier and nerve damage in rats with cerebral small vessel disease by regulating JAK2/STAT3/VEGF signaling pathway.

Objective: To investigate the effect of lycopene on blood-brain barrier and nerve damage in rats with cerebral small vessel disease (CSVD) by regulating Janus kinase 2 (jAK2)/signal transducer and activator of transcription 3 (STAT3 )/vascular endothelial growth factor (VEGF) signaling pathway. Methods: Fifty CSVD rat models were prepared by in vitro injection of the same germ- line microemboli, and were randomly grouped into model group, low-dose lycopene (65 mg/kg) group, high-dose lycopene (85 mg/kg) group, AG490 (JAK2 inhibitor, 3.5 mg/kg) group, and high-dose lycopene (85 mg/kg)+AG490 (3.5 mg/kg) group, with 10 cases in each group, another 10 SD rats were regarded as sham operation group. After grouping with lycopene and AG490, cognitive ability of rats was detected by Morris water maze test and dark avoidance test; permeability of blood-brain barrier in rats was detected by Evans blue method; the number of rat hippocampal neurons was detected by Nissl staining; 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 rats brain tissue were detected by kits; expressions of matrix metalloproteinase (MMP)2, MMP9, tight junction-related proteins (ZO-1, Occludin) and JAK2/STAT3/VEGF pathway-related proteins in rats brain were detected by Western blotting. Results: Compared with 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, levels of CAT and SOD in brain tissue, protein expressions of ZO-1, Occludin and VEGF, and p-JAK2/JAK2, p-STAT3/STAT3 were obviously decreased in model group (P<0.05), while the error times, Evans blue content, levels of brain tissue PGE2, TNF-α and MDA, and protein expressions of MMP2 and MMP9 were obviously increased (P< 0.05). Compared with 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, levels of CAT and SOD in brain tissue, protein expressions of ZO-1, Occludin and VEGF, and p-JAK2/JAK2, p-STAT3/STAT3 were all increased in low-dose lycopene group and high-dose lycopene group (P<0.05), while the error times, Evans blue content, levels of brain tissue PGE2, TNF-α and MDA, and protein expressions of MMP2 and MMP9 were all decreased (P<0.05), and high dose lycopene was 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. Conclusion: Lycopene can inhibit inflammation and oxidative stress in CSVD rats by activating JAK2/STAT3/VEGF signaling pathway, thereby reducing the blood-brain barrier and nerve damage, and improving their cognitive ability. [ABSTRACT FROM AUTHOR]