Effect of sufentanil on blood-brain barrier and nerve damage in hypertensive intracerebral hemorrhage rats by regulating the GAS6/Axl signaling pathway
Objective To investigate the effect of sufentanil(SUF)on the blood-brain barrier and nerve damage in hypertensive intracerebral hemorrhage(HICH)rats by regulating the growth arrest specific protein 6(GAS6)/receptor tyrosine kinase Axl signaling pathway.Methods Healthy SD rats were given a high salt diet for 6 weeks to induce hypertension,and 5 μl of collagenase Ⅳ was injected into the right caudate nucleus of hypertensive rats to construct a HICH model.The HICH model rats were divided into HICH group,L-SUF group,H-SUF group,and H-SUF+AVB-S6-500(GAS6/Axl pathway inhibitor)group.The L-SUF group and H-SUF group were intraperitoneally injected with SUF of 25 and 50 mg/kg every day,while the H-SUF+AVB-S6-500 group were intraperitoneally injected with SUF of 50 mg/kg for two weeks and then followed by AVB-S6-500 of 50 mg/kg.The same batch of hypertensive rats was selected as sham group,which were injected with an equal amount of physiological saline into the right caudate nucleus and peritoneal.cavity.The scores of neurological function damage,blood-brain barrier(BBB)permeability,and BBB structure were analyzed.ELISA was applied to detect the levels of superoxide dismutase(SOD),malondialdehyde(MDA),interleukin-1β(IL-1β),and tumor necrosis factor-α(TNF-α);Wester blot was used to detect the expression of GAS6 and Axl proteins in brain tissue.Results Before drug administration,compared with the sham group,the Longa scores of all other groups were greatly higher(P<0.05),and there was no great difference between these groups(P>0.05).After drug administration,compared with the sham group,the Longa score,BBB permeability,the expression of IL-1β,TNF-α,MDA,GAS6 and Axl proteins in the HICH group were greatly higher,while SOD level was lower(P<0.05),and there was obvious edema,loose cell connections,and uneven endothelial thickness.Both low and high dose SUF can revese these changes mentioned above in HICH rats(P<0.05),while AVB-S6-500 could antagonize the effects of SUF.Conclusion SUF may improve the blood-brain barrier and alleviate nerve damage in HICH rats by activating the GAS6/Axl pathway and inhibiting inflammation and oxidative reactions.
SufentanilGrowth arrest specific gene 6/tyrosine protein kinase receptorHypertensive intracerebral hemorrhageBlood-brain barrierNerve damage
万方数据
维普
