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Association Betwwen Hyperhomocysteinemia And Acute Ischemic Cerebral Disease

Posted on:2003-04-02Degree:DoctorType:Dissertation
Country:ChinaCandidate:X LiFull Text:PDF
GTID:1104360062495202Subject:Neural Science
Abstract/Summary:PDF Full Text Request
Objective: Homocysteine is a thiol-containing amino acid. It is derived from the metabolism of methionine. Marked hyperhomocysteinemia is associated with premature atherosclerosis. Mild to moderate hyperhomocysteinemia has been shown to be a independent risk factor for atherosclerotic and thromboembolic disease. It is not clear whether moderately elevated plasma homocysteine concentration also represents a independent risk factor for stroke, and if so, it is not certain the relation of the homocysteine with the type of ischemic stroke. And it is not clear if elevated plasma homocysteine concentration is correctable by folic acid, and vitamin B6 supplementation. To research into these problems we carried on the case-control study and the animal experiment, to examine the relationship between plasma homocysteine and acute ischemic stroke, to observe the injuring effects of high homocysteine to the vascular and the defending effects of folic acid and vitamin B6.Methods: Fasting plasma homocysteine was measured with high-performance liquid chromatography and fluorescence detection after derivatization of plasma thiols with OPA. Clinical study: We conducted a case-control study of 128 hospital cases with acute ischemic stroke (male 88, female 40, mean age 65.05?0.31 years, age range 37-85 years)and 123 randomly selected healthy controls subjects (male 83, female 40, mean age 55.26 ?7.63 years, age range 38-70years). On thebasis of clinical evaluation and results of imaging studies, the stroke cases were classified into four subtypes: (1) Large-artery disease (single cerebral infarction); (2)Small-artery disease ( lacunar infarction); (3) Cerebral multiinfarction; (4) TIASs. The prevalence of conventional vascular risk factors included age, sex, hypertension, diabetes mellitus, hyperlipidmia, previous TIASs or stroke event, family history and cigarette smoking were inquired. Fasting plasma homocysteine levels, systolic blood pressure, diastolic blood pressure, serum glucose, plasma total cholesterol and triglycerides, plasma fibrinogen and serum BUN were determined in cases and control subjects. Animal experiment: Eighteen male rabbits were randomly divided into three groups, control diet, methionine-rich diet and methionine-rich diet with folic acid and VitB6 treated. Plasma homocysteine levels and serum folic acid levels were measured. Samples were obtained from aorta, carotid artery for histological investigation of light microscope and electron microscope.Results: Clinical study: Mean plasma homocystein of acute ischemic stroke (14.1?.8^mol/l) was significantly higher than control subjects (10.1?.1nmol/l), PO.0001. The elevated plasma homocystein level was related to age and hypertension. The risk factors of acute ischemic strokes include age, hypertension, diabetes mellitus, previous TIASs or stroke events, family history, cigarette smoking and elevated plasma homocystein level. Plasma homocystein level was higher in cases of acute ischemic stroke subtypes due to large-artery disease (single cerebral infarction), cerebral multiinfarction and TIASs compared with control subjects but not in small-artery disease ( lacunar infarction). Animal experiment: Plasmahomocystein level was significantly higher in methionine-rich diet rabbits compared with control and folic acid and VitB6 treated rabbits. Plasma homocystein level was higher in methionine-rich diet rabbits than control rabbits but not higher than methionine-rich diet rabbits. Light microscopic and electron microscopic histological investigation showed degeneration and desquamation of endothelial cells. This denuded intima is seen to be covered by thrombocytes. The smooth muscle cells showed a characteristic processes of hypertrophy , reorientation and hyperplasia.Conclusions: Measurment of plasma homocysteine with high-performance liquid chromatography and fluorescence detection by derivatization of plasma thiols with OPA is a good mean, it is suited to be used in clinical evaluation. Hyperhomocysteinemia is a possible independent risk fa...
Keywords/Search Tags:homocystein, atherosclerosis, ischemic stroke, risk factors, HPLC, folic acid, VitB6
PDF Full Text Request
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