Impact of shikonin on neural function damage in rats with subarachnoid hemorrhage by regulating the HIF-1α/NLRP3 signaling pathway
Objective To investigate the impact of shikonin on neural function damage in rats with subarachnoid hemorrhage(SAH)by regulating the hypoxia inducible factor-1α(HIF-1α)/NOD-like receptor pyrin domain containing 3(NLRP3)signaling pathway.Methods Rats were randomly grouped into the sham surgery group,model group,YC-1(HIF-1α inhibitor,5mg/kg)group,low-dose shikonin group(4mg/kg),high-dose shikonin group(25mg/kg),and high-dose shikonin(25mg/kg)+AG1(HIF-1α activator,10mg/kg)group,with 15 rats per group.The internal carotid artery puncture method was applied to prepare a SAH model.The Zea Longa scoring method was applied to evaluate the neurological function of rats in each group.The enzyme-linked immunosorbent assay(ELISA)method was applied to detect serum levels of tumor necrosis factor alpha(TNF-α),interleukin-6(IL-6),and IL-1β.Morphological changes of hippocampal tissues,apoptosis rate of hippocampal neurons and blood-brain barrier permeability were detected by hematoxylin and eosin(H&E)staining,terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)staining and Evans blue staining,respectively.Commercial reagent kits were used to detect the levels of superoxide dismutase(SOD),malondialdehyde(MDA)and catalase(CAT)in rat brain tissue.Western blot was applied to detect the protein expressions of Bax,Bcl-2,HIF-1α,and NLRP3 in rat brain tissue.Results The morphology and structure of hippocampal neurons in the sham operation group were intact and clear.Compared with those of the sham surgery group,rats in the model group presented a large amount of edema,blurred structure,nuclear dissolution,deformation,pyknosis and the disappearance of some nuclei in hippocampal neurons,significantly higher Zea Longa score,serum TNF-α,IL-6 and IL-1β levels,apoptosis rate of hippocampal neurons,Evans blue exudation amount,MDA level and protein expressions of Bax,HIF-1α,and NLRP3,but significantly lower levels of SOD and CAT and protein expression of Bcl-2(P<0.05).Compared with those of the model group,rats in the low-dose shikonin group,high-dose shikonin group and YC-1 group presented significantly improved pathological damage of rat hippocampal neurons,significantly lower Zea Longa score,serum TNF-α,IL-6 and IL-1β levels,apoptosis rate of hippocampal neurons,Evans blue exudation amount,MDA level and protein expressions of Bax,HIF-1α,and NLRP3,but significantly higher levels of SOD and CAT and protein expression of Bcl-2(P<0.05).Compared with those of the high-dose shikonin group,rats in high-dose shikonin + AG1 group presented significantly higher Zea Longa score,serum TNF-α,IL-6 and IL-1β levels,apoptosis rate of hippocampal neurons,Evans blue exudation amount,MDA level and protein expressions of Bax,HIF-1α,and NLRP3,but significantly lower levels of SOD and CAT and protein expression of Bcl-2(P<0.05).Conclusion Shikonin reduces oxidative stress and inflammatory response by inhibiting the HIF-1α/NLRP3 signaling pathway,thereby improving the neurological damage in SAH rats.
万方数据
维普
