| Objective:The present study was initiated to observe the serum levels of S100 B and high-mobility group protein B1(HMGB1) in patients with atherosclerotic cerebral infarction(ASCI), and investigate the effects of different doses atorvastatin on the serum levels of HMGB1 and S100 B, thus explore the potential anti-inflammatory and neuroprotective effect of statin in cerebral infarction.Methods:Patients with ASCI within 72 hours were randomized to high-dose statin treatment group(atorvastatin 40 mg per day, group A), standard-dose statin treatment group(atorvastatin 20 mg per day, group B) and statin blank group(there was no statin usage within 7 days, group C). Age and sex-matched normal subjects were served as control group(group D). Blood samples were taken from ischemic stroke patients on admission and at 7 days and normal subjects. HMGB1 and S100 B concentrations were measured using an enzyme-linked immune sorbent assay(ELISA), and also determined size of the infarction(magnetic resonance imaging, MRI), neurological function defect of the patients(national institutes of health stroke scale, NIHSS) on admission and at 7 day, self-care ability at three months post-stroke(modified Rankin Scale score, m RS).Results:1) 298 ASCI patients were enrolled in the study. Among these cases, 106 patients were allocated to high-dose statin group, 134 cases to standard-dose statin group, and 58 patients did not receive any statin while in hospital.2) Smoking rates in cases(40.6% in group A, 39.6% in group B and 50.0% in group C)were significantly higher than in control(versus group D 20.9%, p=0.007, 0.008, 0.001).The proportion of anterior circulation infarction of statin blank group(31.0%) were lower than that of statin treatment groups(versus group A 60.4%: c =12.91, p<0.001; versusgroup B 55.6%: c =9.79, p=0.002), and the percentage of lacunar cerebral infarction of statin blank group(37.9%) were higher(versus group A 14.2%: c =12.13, p<0.001, versus group B 14.9%: c =12.34, p<0.001). Accordingly, NIHSS scores of group C on admission(4.69±5.25) were smaller(versus group A 5.77±4.42: p=0.002, and group B 5.08±4.60:p=0.023).3) S100 B concentrations in patients with ASCI on admission were significantly higher compared with normal controls(group A 38.19±30.10, group B 38.41±23.75 and group C32.47±25.04, versus group D 24.57±12.15 pg/L: p=0.006, p<0.001, p=0.048), and had a strong correlation with the volume of cerebral infarction(r=0.272, p=0.004), NIHSS scores on admission(r=0.173, p=0.05) and HDL levels(r =-0.224,p=0.01) respectively. S100 B concentrations at 7 day were evidently decreased compared with that on admission in patients from high-dose statin group(24.91±13.46 versus 38.19±30.10 pg/L, p=0.018) and standard-dose statin group(32.59±24.08 versus 38.41±23.75 pg/L, p=0.057). Conversely,statin blank group had significantly increased higher S100 B concentrations at 7 day than that on admission(45.73± 34.21 versus 32.47±25.04 pg/L, p=0.034). S100 B concentrations at 7 day were associated with serum cystatin C(r=0.164, p=0.045) and NIHSS differences between NIHSS score on admission and that at 7 day(r=-0.166,p=0.036).4) No statistic difference was observed in HMGB1 concentration between cases and normal controls(versus group D 7.43±4.29 pg/L, p>0.05), as well as the HMGB1 levels on admission and at 7 day in patients of cerebral infarction(group A: 6.38±3.21 versus9.51±18.44 pg/L, p>0.05; group B: 5.92±2.30 versus 5.81±1.75 pg/L, p>0.05; group C:8.77±5.60 vs 11.16±12.32 pg/L, p>0.05). However, HMGB1 concentrations had significantly correlations with fasting glucose(r=-0.299, p=0.02) and Hb A1c(r=-0.434,p=0.03).5)NIHSS score differences(NIHSS score on admission-NIHSS score at 7 day)of high-dose statin group(1.63±3.23)were evidently higher than standard-dose statin group and statin blank group(versus 0.89±1.69,p=0.01 and 0.98±1.86,p=0.015).The m RS at three month post-stroke was positively associated with age(r=0.216,p<0.001),volume of cerebral infarction(r=0.294,p<0.001),NIHSS scores on admission and at 7 day(r=0.639,r=0.742,p<0.001),CRP(r=0.169,p=0.004),FIB(r=0.123,p=0.037),D-dimer(r=0.275,p<0.001),neutrophils(r=0.295,p<0.001),and negatively associated with lymphocyte内皮细胞及平滑肌细胞上的晚期糖基化终产物受体(receptor for advanced glycationConclusions:1) S100 B serum levels of cerebral infarction patients within 72 hours significantly increased compared with normal subjects, and correlated with the severity of cerebral infarction.2) No obvious change of HMGB1 concentrations was observed in acute cerebral infarction patients.3) A dose dependent decrease of S100 B levels and neurological function defect was observed in patients received different doses of atorvastatin, which suggests that atorvastatin usage in acute phase of cerebral infarction can improve the early and late outcomes and play neuroproctive and anti-inflammatory role potentially via lowering high level S100 B which behaves itself as a cytokine, amplifying and perpetuating inflammation and causing oxidative damage to neurons.4) Long-term prognosis of patients with cerebral infarction associated with severity of cerebral infarction, age, levels of inflammatory markers and recovery conditions of neurological function. The severer cerebral infarction, older age and higher levels of inflammatory markers predict worse prognosis of ischemic stroke, and the more obviously neurologic impairment improves in acute phase of cerebral infarction, the better prognosis is. |
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