Effect Of Butylphthalide Combined With Atorvastatin On Efficacy And Metabolomics In Patients With Mild Stroke

Objective: This study aims to observe the effect of long-term treatment of butylphthalide combined with atorvastatin on the neurological recovery of light stroke patients with middle cerebral artery stenosis on the responsible side,and to compare the changes of metabolomics levels before and after treatment,so as to provide evidence for the treatment of light stroke patients.Methods: A total of 47 mild ischemic stroke patients with middle cerebral artery stenosis on the responsible side confirmed by MR angiography(MRA)or High-Resolution Magnetic Resonance Imaging(HRMRI)of the intracranial artery(NIHSS≤3 points)who visited the second hospital of Dalian medical university from January 2016 to November2020 were selected.According to the application of sequential butylphthalide therapy,they were divided into butylphthalide combined with an atorvastatin treatment group(dlNBP group)and atorvastatin treatment group(atorvastatin group).All patients were treated according to early management guidelines for acute ischemic stroke;The dl-NBP group was additively injected with butylphthalide injection(100ml twice a day)intravenously.After 7 days,it was changed to a soft butylphthalide capsule(0.2g three times a day)orally on a fasting basis for 3 months.NIHSS,MRS,and ADL scales were used to evaluate the two groups on the first day of admission,before discharge,and 6months after discharge.At the same time,the morning fasting venous blood was collected at admission and 6 months after treatment to detect amino acid metabolism,free fatty acids,and vitamins.The changes of the above indexes before and after treatment were compared to observe whether there were differences between groups.SPSS 25.0statistical software was used for data analysis and processing,and p < 0.05 indicated a statistically significant difference.Results:1.There were no significant differences in the clinical baseline data between the dl-NBP group and the atorvastatin group,including gender,age,history,baseline score(NIHSS,MRS,ADL),blood lipid,homocysteine metabolic pathway,degree of vascular stenosis,and later antiplatelet medication regimen(p > 0.05),and the baseline was stable.2.After treatment,compared with before treatment,NIHSS,MRS,and ADL scores in the dl-NBP group and the atorvastatin group all decreased,with statistical significance(p< 0.05);At 6 months after treatment,the reduction rates of NIHSS,MRS,and ADL in the dl-NBP group and the atorvastatin group were(62.70%/52.82%),(90.48%/66.99%)and(22.11%/18.37%),respectively.The reduction rate of MRS was significant,with statistical significance(p < 0.05).3.Metabolomics(1)Before treatment,there were no significant differences in amino acid metabolism,free fatty acids,vitamin A,vitamin E,and vitamin D between the dl-NBP group and the atorvastatin group(p > 0.05).(2)6 months after treatment compared with before treatmentSerum amino acid determination: glycine and valine in the dl-NBP group were decreased(94.18±19.89/80.39±19.23μmol/L)and(101.06±16.68/88.81±13.07μmol/L),respectively,and the difference was statistically significant(p < 0.05).There was no significant difference in amino acid metabolism in the atorvastatin group(p > 0 0.05).Serum-free fatty acid determination: the palmitic acid in the dl-NBP group was decreased(4214.05±713.87/3898.81±865.76nmol/ m L),while docosahexaenoic acid was increased(372.43±118.42/426.24±152.11nmol/ m L),with statistical significance(p <0.05).In the atorvastatin group,eicosenoic acid increased(13.78±3.58/15.47±4.64nmol/m L),and the difference was statistically significant(p < 0.05).Serum vitamin test: VA in the dl-NBP group was higher than before(0.49±0.16 /0.59±0.17μg/m L),and the difference was statistically significant(p < 0.05).There was no statistical significance in the vitamin difference of the atorvastatin group(p>0 0.05).(3)Six months after treatment,there were statistically significant differences in glycine and valine between the dl-NBP group and the atorvastatin group(p < 0.05),which were(80.39±19.23/97.04±23.11μmol/L)and(88.81±13.07/99.64±13.53μmol/L),respectively.There was statistically significant difference in erucic acid(3.81±3.45/2.23±1.46nmol/m L)in serum free fatty acid(p < 0.05).There was significant difference in VA between the two groups(0.59±0.17/0.49±0.12μg/m L)(p < 0.05).(4)Pearson correlation analysis showed that there was a moderate positive correlation between m RS score and palmitic acid after butylphthalide treatment(r(19)=0.446,p <0.05).Conclusions:1.Long-term application of butylphthalide combined with atorvastatin can promote the recovery of neurological function and can be used as a long-term treatment plan for light stroke patients with middle cerebral artery stenosis the responsible side.2.Butylphthalide combined with Atorvastatin has better efficacy,which may be related to its influence on the metabolism of amino acids(glycine,valine),fatty acids(palmitic acid,docosahexaenoic acid,C20:1,erucic acid),and vitamin(VA),in which butylphthalide has a more prominent effect on the metabolic changes of palmitic acid.