| BackgroundStroke is a kind of brain dysfunction which is caused by organic brain damage resulting from blood circulation disorder,and it is also the main clinical type of cerebrovascular disease(CVD).Stroke is characterized by rapid onset and rapid progression.Stroke can be divided into two categories,including cerebral ischemic stroke(CIS)and cerebral hemorrhagic stroke(CHS).The proportion of CIS can be as high as 4/5,which is the most common type of Stroke.In recent years,with the rapid development of social economy,people’s living standards as well as dietary nutrition have been continuously improved.At the same time,the pace of life is speeding up.The morbidity and mortality of stroke in middle-aged and old people and even young people have increased greatly,and it has become a major disease that endangers human health and safety of life and property.As the main type of CVD,CIS has poor clinical prognosis,high mortality and disability rate.Cerebrovascular stenosis is an important pathological basis for CIS,and the western population is dominated by extracranial Artery stenosis,while the Asian population is dominated by intracranial Artery stenosis,especially middle imaginary artery(MCA)stenosis.After cerebrovascular stenosis,the vascular system can establish a bypass vascular anastomosis network(i.e.,collateral circulation)through regeneration,remodeling and maturity to supply blood to the ischemic area of brain tissue.Effective establishment of cerebral collateral circulation can increase blood perfusion in ischemic area,improve prognosis,reduce mortality and risk of hemorrhagic transformation,and is closely related to the occurrence,development,treatment and prognosis of CIS.Therefore,early assessment of the establishment of cerebral collateral circulation is of great significance for guiding subsequent clinical treatment and estimating the prognosis of patients.Currently,the commonly used methods for evaluating the cerebral collateral circulation,such as digital subtraction angiography(DSA),magnetic resonance agiography(MRA),and computed tomography angiography(CTA),have many shortcomings such as high price,low resolution or complex operation,which limit their clinical application.And so,clinically,we need to have the biological markers that are cheap,convenient and specific to predict the circulatory state of the brain.Sonic hedgehog(SHH)is a regulatory protein widely found in various tissues and organs.Recent studies have found that SHH plays an important role in the process of angiogenesis.Vascular endothelial growth factor(VEGF)plays a powerful role in promoting angiogenesis and is the most widely studied vascular growth factor.Previous animal model experiments have confirmed that SHH and VEGF are closely related to the formation of collateral vessels after cerebral infarction.Therefore,we speculate that SHH and VEGF may also have some relationship with the establishment of collateral circulation in patients with cerebral infarction,which is expected to be a biological indicator to predict the establishment of collateral circulation.However,as far as we know,no literature has been reported on the effect of changes in SHH and VEGF levels on the establishment of collateral circulation in patients with acute ischemic stroke(AIS).In view of the above situation,combined with our previous research results,we designed the study.PurposeThis study aims at clarifying the compensatory mode and opening degree of cerebral lateral circulation in patients with symptomatic MCA stenosis through DSA examination,exploring the effect of serum levels of SHH and VEGF on the establishment of cerebral collateral circulation,and analyzing the potential risk factors affecting the establishment of cerebral collateral circulation,so as to provide theoretical reference for exploring the biological markers of cerebral collateral circulation.MethodsThis study is a single-center case-control study,as a branch subject belonging to the project of "COLLATERAL".From January 2015 to January 2018,a total of 268 patients(189 males and 79 females)with AIS confirmed as Unilateral middle cerebral artery M1segment(MCA-M1)severe stenosis(rate of stenosis≥70%)or occlusion(rate of stenosis=100%)by digital subtract angiography were enrolled from the Department of Neurology,Liaocheng People’s Hospital.According to the ASITN/SIR grading system,the establishment of collateral circulation as shown in DSA was divided into good collateral circulation group and poor collateral circulation group.Level 0～1 is defined as poor collateral circulation and level 2～4 is good collateral circulation.The baseline clinical data,including age,sex,hypertension,diabetes,coronary heart disease,smoking history,drinking history,etc,were collected.The fasting venous blood of the patient was collected in the morning of the next day after admission,and the serum levels of SHH and VEGF were determined by ELISA.At the same time,hypersensitivity-c reactive protein(Hs-CRP),erythrocyte sedimentation rate(ESR),low-density lipoprotein cholesterol(LDL-C),high-density lipoprotein cholesterol(HDL-C),triglyceride(TG),total choles-terol(TC)and homocysteine(Hcy)of patients were examined,and the potential risk factors of cerebral collateral circulation were analyzed statistically.Results(1)Of the 268 patients included in the study,189 were male and 79 were female,with an average age of(64.83±5.62)years old.There were 161 cases of MCA-M1 severe stenosis,among which 114 cases presented collateral compensation,and there were 107 cases of occlusion,of which 94 cases presented collateral compensation,and the difference was statistically significant(P=0.001).There were 292 collateral vessels,including 212(72.6%)of the anterior and posterior arteries,44(15.1%)of the new vessels,20(6.8%)of the anterior and posterior communicating arteries,8(2.7%)of the lateral branches of the external carotid artery,4(1.4%)of the peri-calary artery,and 4(1.4%)of the superficial temporal artery.There were 152 cases(67.7%)in the group with good collateral circulation and 116 cases(42.3%)in the group with poor collateral circulation.(2)There were no statistical significance in the baseline data between the two groups,such as gender,age,coronary heart disease,smoking,drinking,ESR,TC,TG,HDL-C,CRP and Hcy,etc(P>0.05).The prevalence rate of hypertension,diabetes and LDL-C level of the patients in the group with poor collateral circulation were all higher than those in the group with good collateral circulation,and the differences were statistically significant(P<0.05).(3)Compared with the group with poor collateral circulation,SHH and VEGF levels were increased in the group with good collateral circulation(P<0.01).Pearson correlation analysis showed that SHH level was positively correlated with VEGF level(r=0.758,P<0.01).(4)Logistic regression analysis was performed using hypertension,diabetes,LDL-C,SHH and VEGF as independent variables and collateral circulation grading as dependent variables.Statistical results showed that the establishment of collateral circulation was significantly correlated with diabetes(OR=3.094,95%CI:1.321～7.245,P=0.009),SHH level(OR=0.310,95%CI:0.117～0.819,P=0.018)and VEGF level(OR=0.361,95%CI:0.147～0.887,P=0.026),diabetes was an independent risk factor for the establishment of collateral circulation and SHH and VEGF were independent protective factors for the establishment of collateral circulation.Conclusions(1)In AIS patients with severe stenosis or occlusion of MCA-M1,most of the bodies can establish collateral circulation compensation,and the main compensatory way is leptomeningeal collateral circulation.(2)The levels of SHH and VEGF are closely related to the formation of cerebral collateral circulation,and there is a positive correlation between their expression levels,and they are expected to be related biological markers for the clinical evaluation of cerebral collateral circulation compensation.(3)Hypertension,diabetes,and high LDL-C levels may be associated with poor collateral circulation formation,and concurrent diabetes is an independent risk factor for collateral circulation establishment,while SHH and VEGF levels are independent protective factors. |
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