Protective Effects of β-sitosterol on Traumatic University and its Effect on Ferroptosis-lipid Metabolism Pathway in Rats
Objective:To reveal the protective effect of β-sitosterol(Sito)on traumatic brain injury(TBI)rats and its effect on fer-roptosis-lipid metabolism pathway.Methods:Rats were divided into Sham group(n=10),TBI group(n=11),TBI+10Sito group(n=10),TBI+20Sito group(n=10),TBI+40Sito group(n=10)and TBI+40Sito+GPX4-IN-3 group(n=10).The rats in Sham group were not mod-eled.while the rats in other groups were TBI model rats.Rats in Sham group and TBI group were given 1 mL 0.5％carboxymethyl cellu-lose sodium by gastric gavage every day.Rats in TBI+10Sito group,TBI+20Sito group and TBI+40Sito group were given intragastric ad-ministration of β-sitosterol of 1 mL 10,20 and 40 mg/kg/d respectively.Rats in TBI+40Sito+GPX4-IN-3 group were given intragastric administration of[3-sitosterol of 0.5 mL 40 mg/kg/d and GPX4-IN-3 of 0.5 mL 15 mg/kg/d(selective inducer of ferroptosis).Rats in each group were given drugs for 14 days.At the end of administration,the neurological function scores of rats in each group were measured.Cognitive function was evaluated by Morris water maze test.Behavior was evaluated by sucrose preference test and open field experi-ment.The levels of serum lipid metabolism indexes[total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDL-c),high density lipoprotein cholesterol(HDL-c)],brain water content,brain oxidative stress indexes[superoxide dismutase(SOD)and malondialdehyde(MDA)]and brain tissue Fe2+content were measured.Brain injury was evaluated by hematoxylin-eosin(HE)stain-ing and Nissl staining.The protein expression of glutathione peroxidase 4(GPX4)was detected by Western blot and immunofluorescence staining.Results:Compared with Sham group,the neurological function score and escape latency increased,the number of crossing plat-form,sucrose preference rate,horizontal activity score and vertical activity score decreased,TC,TG and LDL-c increased,HDL-c de-creased,brain water content increased,neurons showed obvious damage,SOD level decreased,MDA level increased,Fe2+content in-creased,GPX4 protein expression and GPX4 relative fluorescence intensity decreased in TBI group(P＜0.05).Compared with TBI group,neurological function score and escape latency decreased,the number of crossing platform,sucrose preference rate,horizontal activity score and vertical activity score increased,TC,TG and LDL-c decreased,HDL-c increased,brain water content decreased,neuronal in-jury was significantly alleviated,SOD level increased,MDA level decreased,Fe2+content decreased,GPX4 protein expression and GPX4 relative fluorescence intensity increased in TBI+10Sito group,TBI+20Sito group and TBI+40Sito group(P＜0.05).Compared with TBI+40Sito group,the neurological function score and escape latency increased,the number of crossing platform,sucrose preference rate,horizontal activity score and vertical activity score decreased,TC,TG and LDL-c increased,HDL-c decreased,brain water content increased,neuron injury aggravated,SOD level decreased,MDA level increased,Fe2+content increased,GPX4 protein expression and GPX4 relative fluorescence intensity decreased in TBI+40Sito+GPX4-IN-3 group(P＜0.05).Conclusion:β-sitosterol can effectively re-duce the secondary injury after TBI,and its mechanism may be related to the inhibition of oxidative stress and lipid metabolism disorder mediated by ferroptosis pathway.
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