| Objectives:Explore on the Neuroprotective Effects of high dose statinsinduced heme oxygenase 1(HO-1) expression in patients with ischemic stroke acute stage.Methods:Acute ischemic stroke were researched by prospective cohort study, which admitted to the cohort consistent with the diagnostic criteria and inclusion criteria in neural Department of internal medicine, Kunming General Hospital of Chengdu military region from 2012 October to 2015 February. The patients were randomly divided into high dose group and conventional dose group. On the basis of conventional therapy, high dose group were given atorvastatin calcium 80mg/day, the conventional dose group were given atorvastatin calcium 20mg/day. HO-1 expression measured and neurological deficit score had been operated on admission (DO), third days after admission (D3) and seventh days (D7). Cases were followed up to 90 days (D90), and the rates of adverse events were compared between the two groups. By enzyme-linked immunosorbent assay(ELISA)determination of HO-1,The database was established by EpiData3.0 software, the data was analyzed by the SPSS17.0 software package. The inspection standard was α=0.05.Results:1.Compared to the baseline screeningl35 patients,include 120 patients with,15 cases were exclude,60patients with 1:1 were randomly assigned tot reatment group,60cases in the control group.male 66,female 54 case,accounting for 55.35%,accounting for 44.65%; the maximum age of 74 years,the youngest 46 years,the average age (61.20 ± 5.84) years,87 cases of patients with hypertention,accounting for72.50%;40cases of patients of with diabetes,accounting for 33.33%; 18casesof patients with atrial fibrillation,accounting for 15%;37 smoking patients,accounting for 30.83%.there were nosignificant difference between the two group of indicators.2. HO-1 expression HO-1 expression had no statistical difference with conventional dose group and the high dose group in D0(0.32±0.09ng/mlvs.0.33±0.08 ng/ml,t=1.509, P=0.769).After atorvastatin calcium induced, HO-1 expression of high dose group (80mg/d) were significantly higher than that of the conventional dose group(20 mg/d)in D3 (0.98±0.08 vs.2.16±0.26,t=9.331,P=0.003) and D7 (1.64±0.11 ng/ml vs.3.40±1.21 ng/ml,t=10.835, P<0.01), and HO-1 expression was gradually increased along with the drug administration time lapse. Repeated measures analysis of variance showed that, HO-1 expression of two groups were statistically significant in D0, D3 and D7 (F=21.612, P<0.01; F=25.018, P<0.01). LSD-t test showed that, HO-lexpression of the conventional dose group inD7were higher than DO (t=1.319, P=0.020); HO-lexpression of the high dose group had statistically significant in DO and D3 (t=1.833, P=0.017), DO and D7 (t=3.070, P<0.01), D3 and D7 (t=1.237, P=0.026).The order of HO-1 expression from low to high was DO< D3< D7.3. NIHSS score NIHSS score had no significant difference between the conventional dose group and high dose group in DO (12.79±0.76vs.13.04±0.51,t=1.980, P=0.804). After atorvastatin calcium treatment, NIHSS score of the high dose group (80 mg/d) in D3 and D7 were lower than that of the conventional dose group (20 mg/d)(10.23±0.61vs.8.59±0.48,t=6.803, P=0.029; 6.02±0.45vs.3.41±0.35,t=8.077, P=0.013), and NIHSS score of was gradually reduced along with the drug administration time lapse. Repeated measures analysis of variance showed that, NIHSS score of two groups were statistically significant in D0, D3 and D7 ((F=18.814, P<0.01; F=27.098, P<0.01)). LSD-t test showed that, NIHSS score of the conventional dose group in DO were higher than D7 (t=-6.773,P=0.037), and in D3 were higher than D7 (t=-4.209,P=0.040).NIHSS score of the high dose group had statistically significant in DO and D3 (t=-4.452, P=0.022), DO and D7 (t=-9.630, P<0.01), D3 and D7 (t=-5.178, P=0.012).The order of NIHSS scores from high to low was D0>D3>D7.4. Correlation The correlation analysis showed that, HO-lexpression and the degree of neurologic impairment have a highly negative correlation (r=-0.813, P< 0.01); HO-1 expression and the degree of neurologic impairment have a moderate negative correlation (r=-0.529, P=0.006). Neuroprotective Effects of high dose group than the conventional dose group significantly.5. Prognosis mRS score of the conventional dose group was higher than that of the high dose group (2.67±0.86vs.2.35±0.52, t=8.409,P=0.033).The disability rate of the high dose group lower than that of the conventional dose group (3.33% vs.10%, X2=11.070, P=0.041). The adverse events (including death and disability) rates of the conventional dose group and the high dose group respectively were 13.33% and 3.33%, there was significant difference (X2=12.1360, P=0.036). Non conditional Logistic regression analysis showed that, smoking (OR=1.56, CI95%:1.09～3.48) and hypertension (OR=3.41, CI95%:2.35～6.00) were the promoting factors of acute ischemic stroke with bad prognosis; but high dose atorvastatin (OR=0.64, P=0.03, CI95%:0.14～0.83) was a promoting factor of acute ischemic stroke with favourable prognosis.6.We did not find any serious adverse reactions connected with treatment in the two groups, so we can consider that high dose group and the conventional dose group treatment are both safe and effective.Conclusions:After treatment by atorvastatin calcium, HO-1 expression of high dose group (80mg/d) were significantly higher than that of the conventional dose group (20mg/d), and HO-1 expression was gradually increased along with the drug administration time elapse. Meanwhile, NIHSS score of the high dose group were lower than that of the conventional dose group, and NIHSS score of was gradually reduced along with the drug administration time elapse. HO-1 expression was gradually increased along with the drug dose increasing. The neuroprotection was gradually increased along with the HO-1 expression increasing. High dose atorvastatin calcium could effectively reduce the rates of adverse events with acute ischemic stroke patients. |
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