Relationship Between Cystatin C And Acute Ischemic Stroke And Its Protective Effect

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Correlation analysis between serum Cystatin C and acuteischemic stroke and large cerebral arterial stenosisObjective:To investigate serum Cystatin C levels difference between acute ischemic stroke and control subjects.Furthermore,the correlation between increased serum cystatin C(Cys C)and large cerebral artery stenosis in patients with acute ischemic stroke(AIS)was also analyzed.Methods:Total 252 patients with acute ischemic stroke who were examined with cerebral digital subtraction angiography(DSA)within 7 days stroke from January 2012 to December 2015 in the Second Affiliated Hospital of Soochow University were enrolled in this study.At the same time,75 control subjects were recruited.Large cerebral artery was defined as the internal carotid artery main stem,the middle cerebral artery(M1/M2),and the vertebral artery(V4).Large cerebral artery stenosis was defined as a narrowing of the relevant artery lumen of ?50% or occlusion by viewing cerebral DSA videos.Differences between two groups were determined with Student's T test.A general linear model was used to estimate the relationship between adjusted Cys C values and large cerebral artery stenosis.Bonferroni tests were implemented to correct the error generated by multiple comparisons.The association between large cerebral artery stenosis and Cys C levels were estimated with regression analyses,and the odds ratio(OR)and 95% confidence intervals(CI)were estimated by logistic regression analyses.Patients with large cerebral artery stenosis were divided into 4 groups: vertebral artery stenosis group(VBA stenosis),internal carotid artery stenosis group(ICA stenosis),middle cerebral artery stenosis group(MCA stenosis),and at least 2 large cerebral artery stenosis group(Combined stenosis).Relationship between serum Cys C and the location of stenosis was analyzed.Pearson or Spearman's rank correlation method was used to determine any correlation between plasma Cystatin C levels and all clinical variables.Results:Compared to control subjects,the levels of serum Cys C in patients with AIS significantly increased(P <0.05).Participants(252 cases)included 131 patients(52.0%)without stenosis and 121 patients(48.0%)with large cerebral artery stenosis.Serum Cys C levels in patients with large cerebral artery stenosis were much higher than that of control subjects(P <0.001).Further,logistic regression analyses showed that increased serum Cys C was an independent risk factor of large cerebral artery stenosis in patients with acute ischemic stroke.After the adjustment for age,sex,and smoking,hypertension,type 2 diabetes mellitus(DM),dyslipidemia,creatinine(Cr),urea,uric acid,and C reactive protein(CRP),serum Cys C was highly associated with large cerebral artery stenosis but not the location of large cerebral artery stenosis in patients with AIS.In the ischemic stroke group,correlation analyses among subjects with acute ischemic stroke showed a positive and significant correlation between cystatin C levels and age(r =0.427,P <0.001),urea(r =0.256,P <0.001)and creatinine levels(r =0.608,P <0.001),Uric acid(r =0.293,P <0.001),CRP(r =0.193,P =0.002).Correlation was not observed between cystatin C levels and systolic blood pressure(r =0.066,P =0.299),diastolic blood pressure(r =-0.021,P =0.741),fasting blood glucose level(r =-0.081,P =0.198),triglyceride level(r =-0.001,P =0.991),total cholesterol level(r =-0.009,P =0.889),high-density lipoprotein(HDL)cholesterol level(r =-0.084,P =0.185),and low-density lipoprotein(LDL)cholesterol level(r =0.004,P =0.944).Conclusion:Cystatin C is associated with acute ischemic stroke.A significant positive correlation was observed between elevated serum Cys C levels and large cerebral artery stenosis in patients with acute ischemic stroke.However,serum Cys C levels were not related to the location of stenosis.Part ? The protective effects of exogenous Cystatin C on the cerebralischemic/reperfusion(I/R)injury in miceObjective: At time of 24 h after I/R injury,the level of cystatin C(Cys C)of the brain in a t MCAO mouse model was observed.Observation of neuroprotective effects of Cys C on the ischemic /reperfusion injury in mice was conducted.Methods: The ICR mice were randomly assigned into 4 groups: sham group,Sham+Cys C group,ischemic/reperfusion(I/R)group and I/R+Cys C group.The mouse transient middle cerebral artery occlusion(t MCAO)model was established.The level and expression of Cys C at time of 24 h hour after cerebral I/R injury in a mouse were analyzed by western blotting and immunofluorescence technique.Effects of Cys C pre-treatment on the mice ischemic infarction volume,motor and cognitive function were detected,after intracerebroventricular administration of exogenous Cys C.Results: At 24 h after I/R injury,Cys C level and expression significantly increased,compared with the sham group.After the pre-treatment with 100 ng and 200 ng Cys C,the infarct volumes of the mice were reduced by 32.25% and 27.47% respectviely.Compared with I/R group,pre-treatment with Cys C 100 ng 30min before I/R injury,the time to fall from the rope of rats was significantly increased at 14d(P <0.05);The latency to escape onto the hidden platform was significantly decreased at 21 d(P <0.05).In addition to relieved neurobehavioral function defects,the motor and cognitive function was enhanced in I/R +100ng Cys C pre-treatment group.Conclusion: The present findings provide the evidence that Cys C expression significantly increased at 24 h after I/R injury.Cys C pre-treatment in mice MACO model significantly reduced infarct volume.Furtermore,Cys C pre-treatment alleviated neurobehavioral function,motor and cognitive function defects.These reuslts implicated the existence of neuroprotective effects of exogenous Cys C on I/R injury model in mice.