Effects of dl-3-n-butylphthalide on neurological and endothelial functions and hemorheology in patients with acute cerebral infarction of different CYP2C19 genotypes

Xu Na; Ma Qingchuan; Mu Ni

doi:10.3969/j.issn.1674-7151.2023.04.012

Abstract：Objective To investigate the effects of dl-3-n-butylphthalide on neuralogical and endothelial functions and hemorheology in patients with acute cerebral infarction of different CYP2C19 genotypes.Methods Totally 363 patients with acute cerebral infarction admitted in the neurology department of Tianshui First People's Hospital from January to June 2023 were selected as research objects,and blood samples were collected after continuous administration of dl-3-n-butylphthalide for 5 days.The concentration of dl-3-n-butylphthalide was determined by liquid chromatograph mass spectrometer(LC-MS),and the CYP2C19 genotype was sequenced by second-generation single nucleotide polymorphism(Hi-SNP).The participants were divided into three dl-3-n-butylphthalide metabolism groups based the results of CYP2C19 genotypes:fast group for CYP2C19*1/*1 genotype,intermediate group for CYP2C19*1/*2,CYP2C19*1/*3,CYP2C19*2/*17 and CYP2C19*3/*17 genotypes,and slow group for CYP2C19*2/*2,CYP2C19*3/*3 and CYP2C19*2/*3 genotypes.According to Chinese Guidelines for Diagnosis and Treatment of Acute Ischemic Stroke 2018,neural function and endothelial function indexes[including endothelin-1(EN-1)and nitric oxide(NO)],and hemorheological indexes(including whole blood viscosity and plasma viscosity)were detected.The indexes above-mentioned were compared among three groups.Results The dl-3-n-butylphthalide concentration in slow group was significantly higher than those in fast group and intermediate group(mg/L:0.57±0.09 vs.0.28±0.04,0.12±0.00,both P<0.05),and the dl-3-n-butylphthalide concentration in intermediate group was significantly higher than that in fast group(P<0.05).The total effective rates of fast group,intermediate group and slow group were 52.63%,63.09%and 81.39%,respectively,with statistically difference(P<0.05).The ET-1 concentration in slow group was significantly lower than those in fast group and intermediate group(ng/L:38.56±6.59 vs.65.26±6.36,54.01±5.36,both P<0.05),and the NO concentration in slow group was markedly higher than those in fast group and intermediate group(μmol/L:60.54±5.99 vs.38.71±3.96,49.22±4.51,both P<0.05].In intermediate group,the ET-1 concentration was significantly lower than that in fast group,but the NO concentration was obviously higher than that in fast group(both P<0.05).The levels of high-shear viscosity,low-shear viscosity,plasma viscosity and erythrocyte sedimentation rate(ESR)were significantly lower than those in fast group and intermediate group[high-shear viscosity(mPa·s):5.44±0.51 vs.6.76±0.63,6.07±0.59,low-shear viscosity(mPa·s):8.41±0.82 vs.9.64±0.96,9.02±0.90,plasma viscosity(mPa·s):1.36±0.13 vs.2.46±0.22,1.89±0.19,ESR(mm/h):27.33±2.64 vs.33.56±3.41,30.24±3.22,all P<0.05].However,the indexes in intermediate group were obviously lower than those in fast group(all P<0.05)Conclusions CYP2C19 gene polymorphism has significant effects on nerve function,endothelial function and hemorheology in patients with acute cerebral infarction treated with dl-3-n-butylphthalide.It is of great value to detect CYP2C19 genotype to guide the individualized application of dl-3-n-butylphthalide.