The Effect Of Hydrochloric Fasudil On Serum Inflammatory Factors And Its Therapeutic Efficacy In Acute Ischemic Stroke Patients

Objective:Through determining the serum concentration of Interleukin 6(IL-6), Tumor necrosis factor-α(TNF-α) and S100B in blood in acute ischemic stroke patients, we attempt to find out the relationship among the serum concentration, ischemic stroke subtype based on TOAST(Trail of ORG 10172 in Acute Stroke Treatment) criteria, infarct volume and location of infarction. We also study on serum concentration of the three and association with neurological deficits and functional outcome. Dynamic determination of IL-6, TNF-αand S100B in blood at different points showed time-varying characteristic and positive relationship among the three. By comparing serum concentration of IL-6, TNF-αand S100B before and after Hydrochloric Fasudil treatment and evaluating clinical efficiency in both Fasudil group and routine treatment group, we attempted to discussed the possible role and mechanism of Fasudil, the Rho kinase inhibitor, in Anti- inflammation in acute ischemic stroke patients.Methods: 87 acute ischemic stroke patients were divided into Fasudil group and routine treatment group. There were no significant differences in age, gender, complications and infarct volume. The neurological status and functional outcome in all acute ischemic stroke patients were evaluated by the National Institutes of Health Stroke Scale(NIHSS)and Barthel Index(BI) score on admission and on the 10th day. All patients underwent CT/MRI Scan in 48 hours. Responsibility nidus was confirmed and infarct volume was determined. They were divided into three groups by using Fullicino formula and five stroke subtypes based on TOAST criteria. The therapeutic course in both Fasudil group and routine treatment group was 10 days. The control group was composed of 39 healthy cases. The blood samples were taken on the 1st day,3rdday ,10th day after stroke onset in all stroke patients to separate serum for ELISA detection of IL-6,TNF-αand S100B. The serum concentration of IL-6, TNF-αand S100B was also detected using the same method in control group when they received physical examination. T test, analysis of variance (ANOVA) and Pearson correlation analysis were used to statistics the collected data in SPSS 13.0.Results: (1)The serum concentration of IL-6,TNF-αand S100B in acute ischemic stroke group were significantly higher than in healthy control group on admission. (2)The serum concentration of IL-6, TNF-αand S100B showed positive correlation with the final infarct volume and no correlation with location of infarct. They were higher in subjects with large infarct volume than that with small infarct volume. (3)The serum concentration showed remarkable difference in large-artery atherosclerosis(LAA), small-artery occlusion(SAA) and cardioembolism(CE) subgroups. It was highest in LAA subgroup and lowest in SAA subgroup. (4)The serum concentration of the three showed correlation with each other in acute ischemic stroke patients. (5)The serum concentration of IL-6, TNF-αand S100B showed dynamic changes in acute ischemic stroke patients. They began to increase on admission and reached the peak on the 3rd day, then decreased even lower on the 10th day than on admission in routine treatment group. (6)There was a positive correlation between serum concentration and NIHSS scores on admission and on the 10th day. There was also negative correlation between serum concentration and Barthel Index(BI). So serum concentration of IL-6, TNF-αand S100B can be predictors of neurological deficits and prognosis in early stage of ischemic stroke. (7)Serum concentration of IL-6, TNF-αand S100B in Fasudil group decreased significantly compared with routine treatment group. Routine treatment group showed a higher serum level on the 3rd day than on admission and a lower level on the 10th day. A decreased serum level in Fasudil group was observed on the 3rd day, and the decrease on the 10th day was even more significant than in routine treatment group. (8)In Fasudil group ,the rates of serum concentration reduction in large infarct volume subgroup was more remarkable than that in small infarct volume subgroup,which indicates Fasudil may have a stronger anti-inflammatory effect on severe infarction cases. (9)NIHSS scores on the 10th day in Fasudil group were decreased significantly compared with routine treatment group. BI was obviously improved in Fasudil group, significantly different from those in routine treatment group.Conclusions:IL-6 ,TNF-αand S100B are involved in inflammatory injury in acute cerebral ischemic stroke. They are proved to be sensitive biochemistry markers in early stage after stroke. The serum concentration of IL-6 ,TNF-αand S100B showed dynamic changes in acute phase and had a significant correlation with final infarct volume and stroke subtype according to TOAST criteria. They are also predictors of neurological deficits and prognosis. So they can be used for early diagnosis, as well as evaluation of anti-inflammatory and neuro-protective therapy. Hydrochloric Fasudil,a Rho kinase inhibitor, can reduce the serum level of inflammatory factors, release brain damage and improve neurological deficits and prognosis. It has anti-inflammatory and neuro-protective effects, a wide therapeutic time window and safe using.