The Relationship Between Cerebral Artery Stenosis With Cypa And KLF2 And The Studies Of Cerebral Perfusion With 320 Row CT

Part one The Relationship Between Cerebral Artery Stenosis with CyPA and KLF2BackgroundAtherosclerosis(AS)is an important pathological basis of cerebral artery stenosis.In addition to the mechanism of vascular endothelial injury,more and more attention has been paid to the theory of oxidative stress.Cyclophilin A(CyPA)belongs to the immunophilin protein family.In the condition of oxidative stress,CyPA is stimulated by endothelial cells and secreted into the extracellular.CyPA can promote the expression of adhesion molecules in vascular endothelial cells,promote the infiltration of inflammatory cells,promote smooth muscle cell proliferation and migration,and promote the formation of the vascular wall LDL by regulating the expression of scavenger receptor touptake,eventually,resulting in AS.Kruppel-like factor 2(KLF2)is a member of the Kruppel-like zinc finger transcription factor family.In recent years,it has been found that KLF2 has function of anti-inflammatory,anti adhesion and anti oxidative stress,and also plays an important role in the prevention of AS disease.KLF2 can regulate the expression of pro-inflammatory or anti-inflammatory factors in endothelial cell and inhibit differentiation of adipocyte,prevent proliferation and migration of smooth muscle cell,and maintain the rest of immune cells and blood anticoagulation state,finally resistanting AS.Previous studies have found that the expression of CyPA in vascular endothelial cells of rats was gradually increased while KLF2 decreased with the aggravation of AS lesions,suggesting that elevated CyPA and declined KLF2 may be involved in the formation of AS.But,there is rare research reports about CyPA rare or KLF2 level change in patients with cerebral atherosclerosis stenosis.ObjectiveThe purpose of this part is to probe relationship between cerebral artery stenosis with CyPA and KLF2.Methods1.88 cases subjects were selected from neurology department of Wuhan General Hospital Of Guangzhou Military from October 2015 to October 2016.2.Identify intracranial artery with a narrow rate of>50%or occlusion of the lumen as arterial stenosis.Divided subjects into three groups according to the degree of artery stenosis:control group(no absent stenosis,CG),single intracranial artery stenosis group(SIASG)and multiple intracranial artery stenosis group(MIASG).3.The serum CyPA and KLF2 levels were determined by ELISA method.Other parameters included plasma glucose,blood lipid,glycosylated hemoglobin,homocysteine and uric acid were determined by clinical laboratory of this hosipital.Compare the difference of above parameters and basic data between 3 groups,including age,gender,previous history of stroke,hypertension,hyperlipidemia,diabetes,coronary heart disease,gout history,smoking history and family history of stroke.Analysis of risk factors for intracranial artery stenosis and its relationship with CyPA and KLF2.5.SPSS20.0 statistical analysis software,measurement data in line with the normal distribution were analyze by t test,with a mean +/-standard deviation(+/-SD)description.Basic information such as gender,history of previous stroke were analyze by X2 test,while,age and parameters were analyze byvariance.Using the least significant difference t test in multiple comparison between group.Difference was statistically significant(P<0.05).Results1.Comparison of the basic data of the control group,the single stenosis of intracranial artery and multiple intracranial artery stenosis group.There is significant difference between MIASG and CG in the previous history of stroke,diabetes,coronary heart disease and family history of stroke(39.4%vs 14.8%,P<0.05;39.4%vs 14.8%.P<0.05;18.2%P<0.05;21.3%vs 11.1%,vs 3.7%,P<0.05),namely MIASG patients has significantly higher risk of previous stroke history.There is also significant difference between MIASG and SIASG in coronary heart disease and stroke family history(18.2%vs 0%,P<0.05 21.3%;vs 7.1%,P<0.05),namely MIASG patients has significantly higher risk of coronary heart disease and stroke family history than SIASG patients.2.Comparison of the age and parameters of the control group,the single intracranial artery stenosis group and the multiple intracranial artery stenosis group.There were significantly difference of serum CyPA and KLF2 levels between three groups of patients(0.62 + 0.54 vs 1.37 + 0.61 vs 2.77 + 1.35,P<0.05;1.27 + 0.40 vs 0.82 + 0.26 vs 0.30 + 0.35,P<0.05),namely,MIASG patients have higher level of CyPA than SIASG patients,and they all have higher have higher level of CyPA than CG patients;MIASG patients have lower level of KLF2 than SIASG patients,and they all have lower have higher level of CyPA than CG patients.Conclusion1.Patients with previous history of stroke,history of diabetes,coronary heart disease and family history of stroke were more likely to be associated with intracranial artery stenosis.History of coronary heart disease and family history of stroke may be independent risk factors of intracranial multiple atherosclerotic stenosis.2.The increased serum CyPA and decreased KLF2 may participate in the formation and development of intracranial atherosclerotic stenosis.Part Two Studies of Cerebral Perfusion Imaging in patients with cerebral artery stenosis with 320 row CTBackgroundLow cerebral cerfusion resulted from Cerebral artery stenosis is one of the important causes of ICVD.Cerebral perfusion imaging is the most direct evidence for the evaluation of cerebral ischemia.320 row CT perfusion imaging examination has short examtime,simple operation,lower cost,lower trauma,synchronous angiography and other advantages compared with other perfusion imaging technology.It has important application value for research of cerebral perfusionon in patients with ICVD.Cerebral perfusion study was given priority to the infarction area supplied by stenosis cerebral artery in the past reports,while rare studies of the non-infarction area were reported.The status of cerebral perfusion in addition to vascular stenosis effects,may also be affected by other factors,such as the cerebral collateral circulation,cerebral blood flow and perfusion pressure.In clinical work,we usually found that patients with different degree of cerebral vascular stenosis often have different degrees of cerebral ischemia symptom.We speculate that the cerebral collateral circulation has an important influence on cerebral perfusion.ObjectiveThe purpose of this part is to probe the effect of cerebral collateral circulation on cerebral perfusion in patients with cerebral artery stenosis.Methouds1.46 cases subjects were selected from neurology department of Wuhan General Hospital Of Guangzhou Military from September 2014 to September 2015.All patients were suffered from unilateral middle cerebral artery(MCA)sever stenosis(narrow rate of>70%)or occlusion(narrow rate of 100%)at the beginning or M1 segment.2.All patients completed the CT angiography(CTA)of head and neck combined with CT perfusion imaging(CTP)examination when they were admitted to hospital within one week.3.Divided subjects into two groups according to the collateral circulation score:collateral vessels of more than 50%was defined as the rich collateral group;on the contrary,less 50%was defined as reduced collateral group.4.In the bilateral basal ganglia and radiation level,select MCA cortex with significantly longer TTP(time to peak)as region of interest(ROI).Manually outline the size of ROI,record averaged value of the cerebral perfusion parameters in both sides of brain,including of CBV,CBF,MTT and TTP.Finally,calculate the specific value of the perfusion parameters on both sides(Rcbv,Rcbf,Rttp ratio,Rmtt).5.Statistical analysis.Results1.Comparison of cerebral perfusion between affected side and healthy side of MCA territory in patients with unilateral MCA occlusion.Compared with the contralateral mirror,TTP at ipsilateral affected area was prolonged,CBV and CBF slightly increased and the differences were statistically significant(P<0.05).While MTT was slightly reduced,with no statistically significant difference(P>0.05).That is the ipsilateral cerebral blood perfusion of non infarction is significantly compensatory.2.The difference of cerebral perfusion between rich collateral group and reduced collateral group patients.Among 46 cases patients with unilateral MCA occlusion there were 27 cases in rich collateral group(58.7%)and 19 cases in reduced collateral group(41.3%).Rich collateral circulation group patients have higher Rcbv and Rcbf and lower Rmtt than reduced collateral group patients.,the differences were statistically significant(P<0.05);Rttp was proved no statistically significant differences between two groups(P>0.05).Ipsilateral cerebral perfusion was significantly higher than that That is meaning that rich collateral circulation group patients have more compensatory cerebral perfusion than reduced collateral circulation group decreased.ConclusionTo patients with cerebral artery stenosis,cerebral perfusion in non infarction area is at compensatory state.Rich cerebral collateral circulation can effectively improve cerebral perfusion in patients with ischemic cerebrovascular disease.Part Three Follow-up Studies of Cerebral Perfusion Imaging in patients with cerebral artery stenosis with 320 row CTBackgroundAccording to different cerebrovascular reserve mechanism,cerebral ischemia caused by cerebral artery stenosis can be roughly divided into four periods:collateral circulation reserves stage,cerebral blood flow reserves stage,cerebral metabolic reserve stage and cerebral infarction stage.When cerebral ischemia occured,firstly collateral circulation supply compensatory blood;when the collateral circulation is insufficient to compensate,cerebral arterioles expansion,cerebral blood flow reserve mechanism starts to maintain the normal cerebral blood flow;With further aggravate ischemia,the reserve capacity limits and decompensation,brain tissue uptake capacity to maintain normal brain tissue oxygen metabolism and function by increasing the oxygen,namely the cerebral metabolic reserve stage;Lastly,when the brain tissue oxygen is furtherly reduced,acute stroke or TIA happens.At present,preventive treatment of stroke remains a top priority.Antiplatelet aggregation,stable plaque,and controlling risk factors are still the main,which have been shown to reduce the risk of stroke recurrence.We hypothesized that these treatments may improve the state of cerebral perfusion to a certain extent or maintain cerebral perfusion at compensatory state.At present,research reports are yet found in this regard.ObjectiveThe purpose of this part is to probe the change of cerebral perfusion in patients with cerebral artery stenosis as the course extending in the condition of conventional drug treatment,such as six or twelve months after hospital.Methods1.64 cases of subjects with acute ischemic cerebrovascular disease were selected from neurology department of Wuhan General Hospital Of Guangzhou Military from February 2015 to February 2016.2.All patients were confirmed by cranial 320 row CTA as unilateral MCA severe stenosis or occlusion at the begging or M1 segment in first one week of hospital.3.All patients carry out normaltive secondary prevention treatment after hospital,including antiplatelet aggregation,stable plaques,improve cerebral circulation and control high blood pressure,high cholesterol,diabetes and other risk factors.4.Follow-up patients at 6 months and 12 months after discharge.To know life condition of every patient,whether resuffered cerebral infarction or TIA,conduct the neck + head 320 row CTA and CTP examination again.5.Record mRS scores,degree of vascular stenosis,the condition of collateral circulation,size of cerebral hypoperfusion area and cerebral perfusion parameters value of every patient at the time of discharge,6 and 12 months after discharge.6.Statistical analysis.Results1.Follow-upat 6 months after discharge In the tatal of 64 cases subjucts,56 patients(85.9%)survival well,no recurrence of cerebral infarction or TIA events.11 patients took CTA joint CTP review:collateral circulation condition remained unchange;1 case suffered much more serious vascular stenosis than six months ago,7 cases improved(63.6%)and 3 cases unchanged;2 cases had expanded cerebral hypoperfusion area,7 cases shrinked(60%)and 2 cases unchanged.7 cases were lost to follow-up.2 cases died of centrifuge infarction and cerebral infarction complication respectively.2.Follow-upat 12 months after discharge In 55 patients with longer follow-up,49 cases(89.1%)patients survival well,no recurrence of cerebral infarction or TIA events.19 patients took CTA joint CTP review:collateral circulation condition remained unchange;2 case suffered much more serious vascular stenosis than 12 months ago,3 cases improved and 14 cases unchanged(73.7%);4 cases(21%)had expanded cerebral hypoperfusion area,9 cases shrinked(47.4%)and 6 cases unchanged.5 cases were lost to follow-up.1 cases maybe died of large-area cerebral infarction.3.The comparison of vascular stenosis degree,mRS score,collateral score and the perfusion parameters value at every stage of the patients had no statistical difference(P>0.05),namely,,the lesions in with there were no significant changes in cerebral artery stenosis degree,mRS score,the collateral score and cerebral perfusion parameter values of patients within 1 year after discharge from hospital as the extension of time.Conclusion1.More than 80%of patients with cerebral artery stenosis survival well after 6 months or 12 months of conventional secondary prevention treatment,having low chance of recurrence of cerebral infarction or TIA;2.As the extension of the course,parts of patients with cerebral artery stenosis showed a trend of decreased degree of vascular stenosis and reduced cerebral hypoperfusion area,while,the collateral circulation and cerebral perfusion parameters value showed no obvious change trend.