| Part Ⅰ The effect of cystatin C on acute ischemic strokeObjective: To observe the changes of serum cystatin C(Cys C) in patients of acute ischemic stroke(AIS), and to investigate the role of serum Cys C in the pathogenesis of acute ischemic stroke.Methods: 601 patients with first-ever AIS and 325 control subjects were recruited from November 2012 to December 2014. The general clinical data were compared in the two groups. Logistic regression analyses were done to investigate the association between serum Cys C and AIS. Patients and controls were pooled together to represent an integrated population study and were divided into quintiles by the levels of Cys C. The association between the risk of AIS and serum Cys C was compared among the five subgroups.Spearman’s rank correlation method was used to examine the correlation between serum Cys C level and NIHSS. To explore whether serum Cys C was related to the location of ischemic area, AIS patients were divided into three groups, such as posterior circulation infarction group, anterior circulation infarction group and mixed infarcts group. Serum Cys C was compared between before and after therapy in AIS patients.Results: Serum Cys C levels in patients with AIS(1.01±0.21 mg/L) were significantly higher than in controls(0.95±0.18 mg/L). After adjustment for age, sex, hypertension,diabetes, creatinine, urea, uric acid, triglyceride, HDL, LDL, CRP, logistic regression analyses displayed that elevated Cys C is an independent risk factor of AIS, the odds ratio with 95% confidence interval was 9.80(3.12, 30.83). The total population was divided into quintiles according to the levels of serum Cys C. Compared with the first quintile, the odds ratios(95% confidence interval) of risk for AIS in second and third quintile were 1.07(0.66,1.74) and 1.09(0.67, 1.78), which showed that there were no difference among the first quintile, the second and third quintile. Compared with the first quintile, the odds ratios(95% confidence interval) of risk for AIS in fourth quintile and fifth quintile were1.92(1.08, 3.40) and 2.88(1.49, 5.54), which showed that elevated levels of Cys C were significantly associated with AIS, and the risk of AIS increased with the levels of serum Cys C. Serum Cys C was not connected with NIHSS and the location of ischemic area;however, compared with serum Cys C level before treatment, serum Cys C in patients with AIS significantly decreased after one-week therapy(1.05 ± 0.19 versus 0.99 ± 0.18 mg/L,p<0.001).Conclusions: The levels of serum Cys C in patients with AIS significantly increased in3 days and decreased after one-week therapy. Raised Cys C is an independent risk factor of first-ever ischemic stroke. There was a positive correlation between the risk of AIS and the abnormally elevated serum Cys C levels.Part II The neuroprotective role of cystatin C on cerebralischemia/reperfusion injury in MiceObjective:To observe the levels of cystatin C(Cys C) on ischemic brain injury, and to explore the neuroprotective role of Cys C on the cerebral ischemia/reperfusion injury in mice.Methods:The mouse transient middle cerebral artery occlusion(t MCAO) model was established by using male ICR mice, which were randomly assigned into sham group,ischemic/reperfusion(I/R) group and I/R + Cys C group. The western blotting analysis was done to observe the levels of Cys C within 48 hours after cerebral I/R injury in a mouse MCAO model. The expression of Cys C in the ischemic and non-ischemic cortex was observed by immunohistochemisty staining. The effects of the treatment of Cys C(different dosage) on the cerebral infarct volume and neurobehavioral functions of mice were explored.Results: Cys C expression significantly increased at 6 h after I/R injury, reached a peak at 24 h, and decreased at 48 h after I/R injury. After pretreatment with Cys C, the cerebral infarct volume of the mice was reduced and the neurological deficit was improved significantly. Compared with the I/R group, infarct volume reduced with exogenous Cys C(50 ng for each mice) at 30 min before ischemia(P<0.05) and increased doses of Cys C(100ng or 200 ng) also provided protection on infarct size(P<0.05), which indicated that the neuroprotective effects of exogenous Cys C were dose dependent in a certain concentration range.Conclusion: Cys C expressed significantly increased in the early stage of cerebral I/R injury in a mouse MCAO model and showed a download trend in the late stage. The advanced interfere treatment of exogenous Cys C in mice t MCAO model markedly decreased cerebral infarct volume and relieved neurobehavioral function defects. Cys C exerted neuroprotective effects on ischemic brain injury in mice. |
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