Expression Of Glycoprotein Ibalpha And ADAM17in Acute Ischemic Stroke And Relationship Between These Markers And TCM Syndrome Differentiation

Part One:Changes in platelet GPIba and AD AM17in the acute stage of atherosclerotic ischemic strokeObjective:Glycoprotein (GP)Iba ectodomain shedding has important implications for thrombosis and hemostasis. A disintegrin and metalloproteinase17(ADAM17) was identified to play an essential role in agonist induced GPIba shedding. The relationship of GPIba shedding and ADAM17in the acute stage of atherosclerotic ischemic stroke (AIS) patients has not been thoroughly studied.Methods:306patients and230controls matched for age, sex, race, history of hypertension and diabetes mellitus were enrolled in the study. GPIba, ADAM17, glycocalicin (GC) were detected by flow cytometry, western blotting and enzyme-linked immunosorbent assay (ELISA) respectively.Results:Compared with the control group, the expression of GPIba in acute ischemic stroke patients were significantly lower (P=0.000, P<0.01). The amount of plasma glycocalicin and AD AM17were higher than those in control group (P=0.699, P=0.000), and AD AM17showed significant difference. Pearson’s analysis showed glycocalicin had no correlation with GPIba in AIS patients (r=0.095, P>0.05). GPIba and NIHSS had negative correlation (r=-0.514,P<0.01).Conclusion:Our findings indicate that ADAM17may be a risk factor in AIS patients and the expression of GPIba can serve as a measure for stroke severity. Part Two:Study on the relationship between levels of coagulation markers and TCM syndrome differentiation in ischemic strokeObjective:To observe the relationship between levels of coagulation markers and TCM syndrome differentiation in ischemic stroke and provide theoretical basis for prevention and cure methods on stroke.Methods:306cases of ischemic stroke (merdian stroke) were divided into five types: wind-phlegm blocking collateral type、upward invading of wind-fire type、phlegm-heat with blocked intestines type、wind syndrome due to yin-deficiency type and blood stagnancy due to qi-deficiency type.230cases of healthy people were chosen as control. GPIbα、AD AM17、PLT、MPV、PDW、 coagulation function and homocysteine(Hcy) were detected by drawing blood and analysed according to different TCM syndrome type.Results:(1)Among306patients with ischemic stroke(merdian stroke),33.33%patients were wind-phlegm blocking collateral type,22.22%patients were upward invading of wind-fire type,16.67%patients were phlegm-heat with blocked intestines type,14.71%patients were wind syndrome due to yin-deficiency type and13.07%patients were blood stagnancy due to qi-deficiency type.(2) Among those patients,there were147males(48%) and159females(52%).The average age was63.30±10.76years. There were no significant difference among different TCM syndrome types in sex(X2=2.758, P>0.05)and age(F=0.227, P=0.923, P>0.05).(3) GPIba showed significant difference among five types (F=3.737, P=0.006, P<0.01).There were significant difference between blood stagnancy due to qi-deficiency type and wind-phlegm blocking collateral type (P=0.011, P<0.05)、upward invading of wind-fire type (P=0.001, P<0.01).GPIba of wind syndrome due to yin-deficiency type showed significant difference compared to that of upward invading of wind-fire type(P=0.009, P<0.01).ADAM17showed no significant difference among different types (F=1.008, P=0.403, P>0.05)(4) There were statistical difference in Hcy among different types(F=4.613, P=0.001, P<0.01).There were significant difference between wind-phlegm blocking collateral type and upward invading of wind-fire type、blood stagnancy due to qi-deficiency type、wind syndrome due to yin-deficiency type (P=0.026, P=0.017, P=0.000, P<0.05).Hcy of phlegm-heat with blocked intestines type showed no significant difference compared with that of wind-phlegm blocking collateral type (P=0.051, P>0.05).(5) There were significant difference among different types in MPV (F=2.503, P=0.042, P<0.05).Wind-phlegm blocking collateral type showed significant difference compared to upward invading of wind-fire type and wind syndrome due to yin-deficiency type (P=0.01, P=0.015, P<0.05). There were significant difference among different types in PDW (F=2.515, P=0.042, P<0.05). Wind-phlegm blocking collateral type showed significant difference compared to upward invading of wind-fire type and wind syndrome due to yin-deficiency type (P=0.01, P=0.02, P<0.05).There were no significant difference among wind-phlegm blocking collateral type、blood stagnancy due to qi-deficiency type and phlegm-heat with blocked intestines type (P>0.05)(6) There were no statistical difference among five types in PLT、PT、TT、APTT and INR (P>0.05).Fibrinogen among five types showed significant difference(F=14.143,P=0.000, P<0.01).There were significant difference between wind-phlegm blocking collateral type、 upward invading of wind-fire type、blood stagnancy due to qi-deficiency type and phlegm-heat with blocked intestines type、wind syndrome due to yin-deficiency type (P<0.01).There were no statistical difference among wind-phlegm blocking collateral type%upward invading of wind-fire type and blood stagnancy due to qi-deficiency (P=0.169, P=0.748, P=0.167,P>0.05) (7) There were significant difference in D-dimer among five types (F=2.962, P=0.02, P<0.05). Wind-phlegm blocking collateral type had significant difference compared to upward invading of wind-fire type、phlegm-heat with blocked intestines type and wind syndrome due to yin-deficiency type (P=0.022, P<0.05; P=0.047, P<0.05; P=0.005, P<0.01).Wind syndrome due to yin-deficiency type showed statistical difference compared to blood stagnancy due to qi-deficiency type (P=0.038, P<0.05)(8) In ischemic stroke(meridian stroke),there were negative correlation between GPIb∝and fibrinogen (r=-0.249, P=0.000, P<0.01). Fibrinogen bore positive correlation with D-dimer(r=0.151, P=0.008, P<0.01)Conclusions:(1) In ischemic stroke(meridian stroke), the dominant TCM syndrome type is wind-phlegm blocking collateral type.(2) TCM syndrome type of ischemic stroke(meridian stroke)shows no significant relationship with age、sex、AD AM17、PT、TT、APTT and INR,while has relationship with GPIb∝、Hcy、D-dimer、Fibrinogen、MPV and PDW.(3) The expression of GPIba in upward invading of wind-fire type and wind-phlegm blocking collateral type are higer than other types. The amount of Hcy is the highest in wind-phlegm blocking collateral type.MPV and PDW were high in wind-phlegm blocking collateral type. The amount of fibrinogen were high in wind-phlegm blocking collateral type、upward invading of wind-fire type and blood stagnancy due to qi-deficiency type.Changes of D-dimer in both wind-phlegm blocking collateral type and blood stagnancy due to qi-deficiency type were the most significant.In summary,there were close relationship between levels of coagulation markers and wind-phlegm blocking collateral type、phlegm-heat with blocked intestines type and blood stagnancy due to qi-deficiency type.(4)In ischemic stroke(meridian stroke), there is negative correlation between GPIbaand fibrinogen. Fibrinogen bears positive correlation with D-dimer.