Crocin Treats Posterior Circulation Ischemic Vertigo in Rats via Nrf2/HO-1 Path-way
Objective To study the effect of crocin on posterior circulation ischemic vertigo(PCIV)in rats and to decipher the underlying mechanism based on the nuclear factor E2-related factor 2(Nrf2)/heme oxygenase 1(HO-1)pathway.Methods According to the random number table method,60 SPF male SD rats were assigned into 5 groups:sham,model,crocin(60 mg/kg),ML385(Nrf2 inhibitor,30 mg/kg),and crocin(60 mg/kg)+ML385(30 mg/kg).The rats in other 4 groups except the sham group were modeled for PCIV by ligating the right common carotid artery and the right subclavian artery.After continuous treatment for 1 week in each group once a day,the degree of vertigo was investiga-ted by electrical stimulation escape test.The blood flow of vestibular nucleus,hemorheological indexes[whole blood viscosi-ty(low,middle,and high shear)and plasma viscosity],and erythrocyte parameters[erythrocyte aggregation index(EAI),index of rigidity(IR),hematocrit(HCT),and erythrocyte sedimentation rate(ESR)]were measured.Hematoxylin-eosin staining was employed to observe the pathological changes of the brain tissue.The levels of lactic acid(Lac),lactate dehy-drogenase(LDH),interleukin(IL)-1 β,IL-6,tumor necrosis factor-α(TNF-α),and malondialdehyde(MDA)and the activities of superoxide dismutase(SOD)and catalase(CAT)in the brain tissue were measured.Western blotting was em-ployed to determine the protein levels of Nrf2 and HO-1 in the brain tissue,nuclear factor κB p65(NF-κB p65)in the cytoplasm,and NF-κB p65 in the nucleus.Results Compared with the model group,crocin shortened the electrical stim-ulation escape latency,increased the blood flow of vestibular nucleus,decreased the whole blood viscosity,plasma viscosi-ty,EAI,IR,HCT,and ESR,and alleviated the pathological changes such as loose brain tissue structure,reduced neurons,vacuolar degeneration,nuclear deviation,and unclear nuclear membrane boundary.Moreover,crocin lowered the levels of Lac,LDH,IL-1 β,IL-6,TNF-α,and MDA in the brain tissue,increased the activities of SOD and CAT,up-regulated the expression of Nrf2 and HO-1,down-regulated the expression of NF-κB p65 in the nucleus,and decreased the ratio of nuclear NF-κB p65 to cytoplasmic NF-κB p65(all P＜0.05).The effect of ML385 was opposite to that of crocin,and the changes of vertigo symptoms and other indicators in the ML385 group were more serious than those in the model group.ML385 obviously reversed the alleviating effects of crocin on vertigo symptoms,blood flow of vestibular nucleus,and expression of Nrf2,HO-1,and nuclear NF-κB p65 in the rat model of PCIV.Conclusion Crocin can alleviate vertigo symptoms,recover the blood flow of vestibular nucleus,inhibit inflammatory response and oxidative stress,and reduce brain tissue damage in the rat model of PCIV by activating the Nrf2/HO-1 pathway and inhibiting the NF-κB nuclear translo-cation.
CrocinPosterior Circulation Ischemic VertigoBlood Flow of Vestibular NucleusNrf2/HO-1 Path-wayNF-κB
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