|
| Protective effect of crocin on the blood-brain barrier of rat with cerebral ischemia reperfusion through Nrf2/HO-1 pathway |
| Hits 457 Download times 274 Received:March 15, 2022 |
| View Full Text View/Add Comment Download reader |
| DOI
10.11656/j.issn.1672-1519.2022.08.22 |
| Key Words
crocin;cerebral ischemia-reperfusion;BBB;inflammation;oxidative stress;Nrf2/HO-1 pathway |
| Author Name | Affiliation | | YANG Huanhuan | Third Hospital of Shijiazhuang, Shijiazhuang 050011, China | | DUAN Yi | Third Hospital of Shijiazhuang, Shijiazhuang 050011, China |
|
| Abstract
|
| [Objective] To investigate the protective effect and mechanism of crocin on the blood-brain barrier (BBB) of rats with cerebral ischemia-reperfusion. [Methods] According to the random number table method,240 healthy SD rats were divided into sham operation group,model group,low (10 mg/kg),medium (20 mg/kg),high (40 mg/kg) dose crocin group and nimodipine (2 mg/kg) group,40 in each group. The cerebral ischemia-reperfusion rat models were replicated by clamping the middle cerebral artery for 2 hours. The 7 days before the model operation,the drugs were injected intraperitoneally once a day,and the rats in sham operation group and model group were given 0.9% sodium chloride solution. The 24 h after reperfution,the neurological deficit score was performed,the brain tissue infarction rate was calculated by red tetrazolium (TTC) staining method,the water content of brain tissue was detected by weightlessness method；the pathological changes of brain tissue was observed through HE staining；the BBB permeability was detected by evans blue permeation method；the content of tumor necrosis factor-α (TNF-α),interleukin-1β (IL-1β),interferon-γ (IFN-γ) were detected by ELISA method；the content of malondialdehyde (MDA) and the activity of superoxide dismutase (SOD),talase (CAT) in brain tissue were detected by spectrophotometry method；the expression of Occludin,zonula occludens-1 (ZO-1),nuclear factor E2 related factor 2 (Nrf2),heme oxygenase 1 (HO-1),cytoplasmic nuclear factor-κB p65 (cytoplasmic NF-κB p65),nucleus NF-κB p65 in brain tissue were detected by Western blot method. [Results] Compared with the sham operation group,the neurological deficit score,infarction rate, water content of the rats in model group were increased (P<0.05)；the brain tissue presents pathological changes such as edema, decreased neuron number, vacuolar degeneration,nucleus deviation,pyknosis and hyperchromatism,inflammatory cell infiltration；the penetration of evans blue in brain tissue was increased (P<0.05)；the content of TNF-α,IL-1β,IFN-γ,MDA in brain tissue were increased while the activity of SOD,CAT were decreased (P<0.05)；the expression of Occludin,ZO-1,Nrf2,HO-1 were decreased,while the expression of cytoplasmic NF-κB p65,nuclear NF-κB p65 and the ratio of nuclear NF-κB p65/cytoplasmic NF-κB p65 were increased (P<0.05). Compared with the model group,the neurological deficit score,infarction rate,water content of the rats in medium,high dose crocin group and nimodipine group were significantly decreased (P<0.05)；the pathological changes of brain tissue was improved；the penetration of evans blue in brain tissue was decreaed (P<0.05)；the content of TNF-α,IL-1β,IFN-γ,MDA in brain tissue were decreased while the activity of SOD,CAT were increased (P<0.05)；the expression of Occludin,ZO-1,Nrf2,HO-1 were increased,while the expression of cytoplasmic NF-κB p65,nuclear NF-κB p65 and the ratio of nuclear NF-κB p65/cytoplasmic NF-κB p65 were decreased (P<0.05). [Conclusion] Crocetin has a certain protective effect on the structure and permeability of BBB in rats with cerebral ischemia-reperfusion, and can reduce brain tissue damage；which mechanism may be related to activation of Nrf2/HO-1 pathway and inhibition of NF-κB into the nucleus,and thereby inhibiting oxidative stress and inflammation. |
|
|
|
|
|
|
|
