d-Serine administration provokes lipid oxidation and decreases the antioxidant defenses in rat striatum

The present work investigated the effects of intrastriatal administration of d-serine on relevant parameters of oxidative stress in striatum of young rats. d-Serine significantly induced lipid peroxidation, reflected by the significant increase of thiobarbituric acid-reactive substances, and significantly diminished the striatum antioxidant defenses, as verified by a decrease of the levels of reduced glutathione and total antioxidant status. Finally, d-serine inhibited superoxide dismutase activity, without altering the activities of glutathione peroxidase and catalase. In contrast, this d-amino acid did not alter sulfhydryl oxidation, a measure of protein oxidative damage. The present data indicate that d-serine in vivo administration induces lipid oxidative damage and decreases the antioxidant defenses in the striatum of young rats. Therefore, it is presumed that this oxidative stress may be a pathomechanism involved at least in part in the neurological damage found in patients affected by disorders in which d-serine metabolism is compromised, leading to altered concentrations of this d-amino acid.     

Homocysteine, reactive oxygen species and nitric oxide in type 2 diabetes mellitus

INTRODUCTION: Type 2 diabetes mellitus shows a characteristic altered platelet function that can be due to several mechanisms such as oxidative stress. Hyperhomocysteinemia, considered as a risk factor for various arterial thrombosis, may have a role in generating oxidative damage, even if the pathogenic mechanisms are still not clear. In this report we aimed to determine the role of plasma homocysteine in inducing oxidative stress in type 2 diabetes mellitus. MATERIALS AND METHODS: The study was performed on a group of 34 males with type 2 diabetes and 36 healthy subjects matched for sex and age. Patients and healthy subjects were undergone to laboratory evaluation for plasma homocysteine levels and other metabolic parameters. In both groups of subjects platelet reactive oxygen species, nitric oxide and guanosine 3',5' cyclic monophosphate levels were measured. Moreover the reduced glutathione content in platelets of patients and of healthy subjects was assayed. RESULTS: Plasma homocysteine levels were significantly increased in patients compared with healthy subjects. The basal level of reactive oxygen species was significantly higher in patients than in controls. In addition platelets of patients stimulated with thrombin produced more reactive oxygen species than healthy subjects ones. The nitric oxide, guanosine 3',5' cyclic monophosphate and reduced glutathione content were decreased in platelets of patients. CONCLUSIONS: As homocysteine stimulates oxidative stress and inhibits nitric oxide formation, hyperhomocysteinemia measured in type 2 diabetic patients, promoting platelet hyperactivity, could have a role in the atherogenic effects described in type 2 diabetes.     

Concurrent folate treatment prevents Na,K-ATPase activity inhibition and memory impairments caused by chronic hyperhomocysteinemia during rat development

We investigated the hypothesis that folate administration would prevent hyperhomocysteinemia-induced memory deficits and Na⁺,K⁺-ATPase activity inhibition. Chronic hyperhomocysteinemia was induced from the 6th to the 28th day of life by subcutaneous injection of homocysteine (0.3–0.6 μmol/g), twice a day; control Wistar rats received the same volume of saline solution (0.9% NaCl). Half of the homocysteine- and saline-treated groups also received intraperitoneal administration of folate (0.011 μmol/g) from the 6th to the 28th day of life. A group of animals was killed 12 h after the last injection, plasma and parietal cortex were collected for biochemical analysis. Another group stayed at Central Animal House until 60th day of life, when the rats were submitted to behavioral testing in water maze or were killed for evaluation of cortical Na⁺,K⁺-ATPase activity. Results showed that hyperhomocysteinemia impaired reference memory for platform location, as assessed by fewer crossings to the platform place and increased latency for the first crossing, when compared to controls. In the working memory task homocysteine-treated animals also needed more time to find the platform. We also observed that Na⁺,K⁺-ATPase activity was reduced in parietal cortex of hyperhomocysteinemic rats sacrificed 12 h after the last injection of homocysteine (29-day-old rats). In contrast, this enzyme was not altered when the rats were sacrificed 31 days after the treatment (60-day-old rats). Hyperhomocysteinemic rats treated with folate had all those impairments prevented, an effect probably related to folate antioxidant properties.     

Evaluation of oxidative status and depression-like responses in Brown Norway rats with acute myeloid leukemia

It has been proved that oxidative stress increases when leukemia is accompanied by depression. This fact may indicate the role of oxidative stress in the development of depression in cancer patients. The aim of this study was to determine whether the acute myeloid leukemia of Brown Norway rats, which is accompanied by oxidative stress, evoked behavioral and receptor changes resembling alterations characteristic of rat models of depression. The rats were divided into two groups: leukemic rats and healthy control. Leukemia was induced through intraperitoneal injection of 10⁷ promyelocytic leukemia cells to the Brown Norway rats. Depression-like behavior was evaluated in the forced swim test at 30 or 34 days after leukemic cells injection. The rats were killed after the evaluation and the spleen, brain cortex and hippocampus were excised. The red–ox state was assessed in homogenates of tissues by measuring total glutathione (GSH) content, the ferric ion reducing ability of plasma (FRAP) level, expression of heme oxygenase-1 (HO-1), biliverdin reductase (BvR) and ferritin mRNA, superoxide dismutase (SOD) activity, as well as malondialdehyde (MDA) concentration. Radioligand binding assay was used to assess of the effect of leukemia on cortical receptors. Leukemic cells were identified using RM-124 antibody by FACS Calibur flow cytometry. Leukemia influenced locomotory activity as well as forced swim test behavior in a 34-day series of experiments. Signs of oxidative stress in leukemic rats were observed in each examined stage of leukemia development. The FRAP values and glutathione contents, were significantly lowered whereas HO-1 mRNA expression, and malonodialdehyde concentrations were significantly increased in the spleen and brain structures of leukemic rats in comparison with the healthy controls. A significant increase in the potency of glycine to displace [³H]L-689,560 from the strychnine-insensitive glycine site of the N-methyl-D-aspartic (NMDA) receptors receptor complex in cortical homogenates of the leukemic rats in 30- and 34-day experimental series was observed in comparison with the control. Upregulation of 5-HT_2A receptors was observed in rat cortex after 30 days of leukemia development but not in 34-days series compared with the control. It is concluded that disturbances in antioxidant system in brain cortex were accompanied by an activation of glycine sites of the NMDA receptor complex, regardless of stage of leukemia development, which are characteristic of model of depression. Findings of our study demonstrate the link between glutamatergic activity, oxidative stress and leukemia.     

Reduction of lipid and protein damage in patients with disorders of propionate metabolism under treatment: a possible protective role of l-carnitine supplementation

Disorders of propionate metabolism are autosomal recessive diseases clinically characterized by acute metabolic crises in the neonatal period and long-term neurological deficits whose pathophysiology is not completely established. There are increasing evidences demonstrating antioxidant properties for l-carnitine, which is used in the treatment of propionic and methylmalonic acidemias to increase the excretion of organic acids accumulated in tissues and biological fluids of the affected patients. In this work we aimed to evaluate lipid (malondialdehyde content) and protein (carbonyl formation and sulfhydryl oxidation) oxidative damage in plasma from patients with propionic and methylmalonic acidemias at the moment of diagnosis and during treatment with l-carnitine. We also correlated the parameters of oxidative damage with plasma total, free and esterified l-carnitine levels. We found a significant increase of malondialdehyde and carbonyl groups, as well as a reduction of sulfhydryl groups in plasma of these patients at diagnosis compared to controls. Furthermore, patients under treatment presented a marked reduction of the content of protein carbonyl groups, similar to controls, and malondialdehyde content in relation to patients at diagnosis. In addition, plasma total and free l-carnitine concentrations were negatively correlated with malondialdehyde levels. Taken together, the present data indicate that treatment significantly reduces oxidative damage in patients affected by disorders of propionate metabolism and that l-carnitine supplementation may be involved in this protection.     

Folic acid pretreatment prevents the reduction of Na(+),K(+)-ATPase and butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia.

The main objective of the present study was to evaluate the effect of folic acid pretreatment on parietal cortex Na(+),K(+)-ATPase and serum butyrylcholinesterase activities in rats subjected to acute hyperhomocysteinemia. Animals were pretreated daily with an intraperitoneal injection of folic acid (5 mg/kg) or saline from the 22th to the 28th day of age. Twelve hours after the last injection of folic acid or saline, the rats received a single subcutaneous injection of homocysteine (0.6 micromol/g of weight body) or saline and were killed 1h later. Serum was collected and the brain was quickly removed and parietal cortex dissected. Results showed that acute homocysteine administration significantly decreased the activities of Na(+),K(+)-ATPase and butyrylcholinesterase on parietal cortex and serum, respectively. Furthermore, folic acid pretreatment totally prevented these inhibitory effects. We also evaluated the effect of acute homocysteine administration on some parameters of oxidative stress, namely thiobarbituric acid-reactive substances and total thiol content in parietal cortex of rats. No alteration of these parameters were observed in parietal cortex of homocysteinemic animals, indicating that these oxidative stress parameters were probably not responsible for the reduction of Na(+),K(+)-ATPase and butyrylcholinesterase activities. The presented results confirm previous findings that acute hyperhomocysteinemia produces an inhibition of Na(+),K(+)-ATPase and butyrylcholinesterase activities and that pretreatment with folic acid prevents such effects. Assuming that homocysteine might also reduce the activities of these enzymes in human beings, our results support a new potential therapeutic strategy based on folic acid supplementation to prevent the neurological damage found in hyperhomocysteinemia.     

In vivo and in vitro effects of homocysteine on Na,K-ATPase activity in parietal, prefrontal and cingulate cortex of young rats

In the present study we determined the effect of chronic administration of homocysteine on Na+,K+-ATPase activity in synaptic membranes from parietal, prefrontal and cingulate cortex of young rats. We also studied the in vitro effect of homocysteine on this enzyme activity and on some oxidative stress parameters, namely thiobarbituric acid-reactive substances (TBA-RS) and total radical-trapping antioxidant potential (TRAP) in the same cerebral structures. For the in vivo studies, we induced elevated levels of homocysteine in blood (500 microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young rats by injecting subcutaneously homocysteine (0.3-0.6 micromol/g of body weight) twice a day at 8 h intervals from the 6th to the 28th postpartum day. Controls received saline in the same volumes. Rats were killed 12 h after the last injection. Chronic administration of homocysteine significantly decreased (50%) Na+,K+-ATPase activity in parietal, increased (36%) in prefrontal and did not alter in cingulate cortex of young rats. In vitro homocysteine decreased Na+,K+-ATPase activity and TRAP and increased TBA-RS in all cerebral structures studied. It is proposed that the alteration of Na+,K+-ATPase and induction of oxidative stress by homocysteine in cerebral cortex may be one of the mechanisms related to the neuronal dysfunction observed in human homocystinuria.     

Folic acid supplementation attenuates hyperhomocysteinemia-induced preeclampsia-like symptoms in rats

Folic acid participates in the metabolism of homocysteine and lowers plasma homocysteine levels directly or indirectly.To establish a hyperhomocysteinemic pregnant rat model,2 mL of DL-homocysteine was administered daily by intraperitoneal injection at a dose of 200 mg/kg from day 10 to day 19 of gestation.Folic acid was administered by intragastric administration at a dose of 20 mg/kg during the period of preeclampsia induction.Results showed that systolic blood pressure,proteinuria/creatinine ratio,and plasma homocysteine levels in the hyperhomocys-teinemic pregnant rats increased significantly,and that body weight and brain weight of rat pups significantly decreased.Folic acid supplementation markedly reversed the above-mentioned abnormal changes of hyperhomocysteinemic pregnant rats and rat pups.These findings suggest that folic acid can alleviate the symptoms of hyperhomocysteinemia-induced preeclampsia in pregnant rats without influencing brain development of rat pups.     

Pro-thrombotic and pro-oxidant effects of diet-induced hyperhomocysteinemia

Elevated plasma homocysteine levels are associated with the risk of atherosclerosis and arterial and venous thrombosis. We have previously demonstrated that rabbits rendered hyperhomocysteinemic by parenteral administration of homocysteine develop a dysfibrinogenemia that is associated with the formation of fibrin clots that are abnormally resistant to fibrinolysis. We suggested that this acquired dysfibrinogenemia contributes to the thrombotic tendency in hyperhomocysteinemia. However, it was possible that the homocysteine-associated dysfibrinogenemia was an artifact of the parenteral administration model. Therefore, the goals of the current study were to develop a diet-induced model of homocysteinemia in rabbits and determine whether a dysfibrinogenemia and evidence of oxidative stress develop in this model as they do when homocysteine is injected. We found that rabbits fed a diet severely deficient in folate and mildly deficient in choline develop mild hyperhomocysteinemia: 14.8+/-4.0 microM in deficient rabbits compared to 9.0+/-1.7 microM in controls. The deficient rabbits also develop evidence of oxidant stress: increased lipid peroxidation in liver, impaired mitochondrial enzyme activities in liver and elevated caspase-3 levels in plasma. Most importantly, the deficient rabbits also develop a dysfibrinogenemia characterized by increased resistance to fibrinolysis. We believe that this dietary model of homocysteinemia is clinically relevant and reproduces many features associated with hyperhomocysteinemia in previous work using in vitro and in vivo models. Our findings suggest that an acquired dysfibrinogenemia could play a role in the increased risk of atherothrombotic disease in mildly hyperhomocysteinemic human subjects.     

Physical exercise reverses glutamate uptake and oxidative stress effects of chronic homocysteine administration in the rat

The influence of physical exercise on the effects elicited by homocysteine on glutamate uptake and some parameters of oxidative stress, namely thiobarbituric acid-reactive substances, 2',7'-dichlorofluorescein (H(2)DCF) oxidation, as well as enzymatic antioxidant activities, superoxide dismutase, catalase and glutathione peroxidase in rat cerebral cortex were investigated. Wistar rats received subcutaneous administration of homocysteine or saline (control) from the 6th to 29th day of life. The physical exercise was performed from the 30th to 60th day of life; 12 h after the last exercise session animals were sacrificed and the cerebral cortex was dissected out. It is shown that homocysteine reduces glutamate uptake increases thiobarbituric acid-reactive substances and disrupts enzymatic antioxidant defenses in cerebral cortex. Physical activity reversed the homocysteine effects on glutamate uptake and on antioxidant enzymes activities; although the increase in thiobarbituric acid-reactive substances was only partially reversed by exercise. These findings allow us to suggest that physical exercise may have a protective role against homocysteine-induced oxidative imbalance and brain damage to the glutamatergic system.     

The anti-oxidant and anti-apoptotic effects of nebivolol and zofenopril in a model of cerebral ischemia/reperfusion in rats

The aim of this experiment was to investigate whether nebivolol and zofenopril have protective effects against oxidative damage and apoptosis induced by cerebral ischemia/reperfusion (I/R).There were seven groups of rats, with each containing eight rats. The groups were: the control group, I/R group, I/R plus zofenopril, I/R plus nebivolol, I/R plus nebivolol and zofenopril, zofenopril only and nebivolol only. Cerebral I/R was induced by clamping the bilateral common carotid artery and through hypotension. The rats were sacrificed 1 h after ischemia, and histopathological and biochemical analyses were carried out on their brains. The total antioxidant capacity was evaluated by using an automated and colorimetric measurement method developed by Erel. I/R produced a significant increase in the levels of total oxidant status and malondialdehyde levels, the number of caspase-3 immunopositive cells and activities of prolidase and paraoxonase in brain when compared with the control group (p < 0.05). A significant decrease in brain total antioxidant capacity and nitric oxide levels were found in I/R group when compared with the control group (p < 0.05). Both nebivolol and zofenopril treatment prevented decreasing of the total antioxidant capacity and nitric oxide levels, produced by I/R in the brain (p < 0.05). Both nebivolol and zofenopril treatment prevented the total oxidant status, malondialdehyde levels, activities of paraoxonase and prolidase from increasing in brains of rats exposed to I/R (p < 0.05).In conclusion, both nebivolol and zofenopril protected rats from ischemia-induced brain injury. The protection may be due to the indirect prevention of oxidative stress and apoptosis.     

Chronic Mild Hyperhomocysteinemia Alters Inflammatory and Oxidative/Nitrative Status and Causes Protein/DNA Damage,as well as Ultrastructural Changes in Cerebral Cortex: Is Acetylsalicylic Acid Neuroprotective?

Homocysteine is a sulfur-containing amino acid derived from methionine metabolism. When plasma homocysteine levels exceed 10–15 μM, there is a condition known as hyperhomocysteinemia, which occur as a result of an inborn error of methionine metabolism or by non-genetic causes. Mild hyperhomocysteinemia is considered a risk factor for development of neurodegenerative diseases. The objective of the present study was to evaluate whether acetylsalicylic acid has neuroprotective role on the effect of homocysteine on inflammatory, oxidative/nitrative stress, and morphological parameters in cerebral cortex of rats subjected to chronic mild hyperhomocysteinemia. Wistar male rats received homocysteine (0.03 μmol/g of body weight) by subcutaneous injections twice a day and acetylsalicylic acid (25 mg/Kg of body weight) by intraperitoneal injections once a day from the 30th to the 60th postpartum day. Control rats received vehicle solution in the same volume. Results showed that rats subjected to chronic mild hyperhomocysteinemia significantly increased IL-1β, IL-6, and acetylcholinesterase activity and reduced nitrite levels. Homocysteine decreased catalase activity and immunocontent and superoxide dismutase activity, caused protein and DNA damage, and altered neurons ultrastructure. Acetylsalicylic acid totally prevented the effect of homocysteine on acetylcholinesterase activity and catalase activity and immunocontent, as well as the ultrastructural changes, and partially prevented alterations on IL-1β levels, superoxide dismutase activity, sulfhydryl content, and comet assay. Acetylsalicylic acid per se increased DNA damage index. In summary, our findings showed that chronic chemically induced model of mild hyperhomocysteinemia altered some parameters and acetylsalicylic acid administration seemed to be neuroprotective, at least in part, on neurotoxicity of homocysteine.     

Effects of maternal hyperhomocysteinemia induced by methionine intake on oxidative stress and apoptosis in pup rat brain

Maternal hyperhomocysteinemia is associated with a number of complications such as preeclampsia syndrome, thromboembolic events, repeated miscarriages, abruptio placentae, in utero fetal death, intrauterine fetal growth restriction and fetal neural tube defects. However, little is known about the mechanism of homocysteine on the degeneration of fetal brain. Thus, our study is aimed to investigate the effects of maternal hyperhomocysteinemia on oxidative stress and apoptosis in pup brain. Hyperhomocysteinemia was induced in female rats by way of administrating methionine dissolved in water at a dose of 1 g/kg body weight throughout the pregnancy. After delivery, level of lipid peroxidation (LPO; as malondialdehyde + 4-hydroxyalkenals) was determined in various fractions of pub brains. Furthermore, DNA fragmentation, levels of Bcl-2 protein and p53 mRNA expression were determined to evaluate apoptosis. Significant elevation was found in the levels of LPO in subcellular fractions of pup brains delivered from hyperhomocysteinemic mothers. DNA fragmentation, a hallmark of apoptosis was observed in the brain of pups of homocysteine group while significant reduction was seen in the levels of anti-apoptotic Bcl-2 levels. In addition, maternal hyperhomocysteinemia increased cerebral p53 mRNA expression above the control value. As a conclusion, we demonstrate and suggest that the pups of hyperhomocysteinemic mothers have an increased oxidative stress in brain tissues. The increased oxidative stress appears to cause apoptosis and cell death. These results may be significant to understand chronic pathology of the complications of hyperhomocysteinemia and congenital malformations of fetuses.     

Total antioxidant capacity is impaired in different structures from aged rat brain

Our data support a disproportion between free radicals levels and scavenging systems activity in different cerebral regions of the aging rat. We investigated the total reactive antioxidant potential and reactivity levels, which represent the total antioxidant capacity, in different cerebral regions of the aging rat (cortex, striatum, hippocampus and the cerebellum). In addition, we have determined several oxidative stress parameters, specifically the free radicals levels, the macromolecules damage (lipid peroxidation and carbonyl content), as well as the antioxidant enzymes activities in different cerebral areas from young (2 months-old), mature adult (6 months-old) and old (24 months-old) male Wistar rats. Free radicals levels, determined by 2′,7′-dichlorofluorescein diacetate probe, were higher in striatum, cerebellum and hippocampus from aged rats. There was an age-related increase in lipoperoxidation in hippocampus and cerebral cortex. In the cerebellum, a high activity of superoxide dismutase and a decrease of catalase activity were observed. The striatum exhibited a significant catalase activity decrease; and glutathione peroxidase activity was diminished in the hippocampus of mature and aged rats. There was a marked decrease of total antioxidant capacity in hippocampus in both reactivity and potential levels, whereas striatum and cerebral cortex displayed a reduction on reactivity assay. We suggest that age-related variations of total antioxidant defenses in brain may predispose structures to oxidative stress-related neurodegenerative disorders.     

Development of an animal model for chronic mild hyperhomocysteinemia and its response to oxidative damage

The purpose of this study was to develop a chronic chemically induced model of mild hyperhomocysteinemia in adult rats. We produced levels of Hcy in the blood (30 μM), comparable to those considered a risk factor for the development of neurological and cardiovascular diseases, by injecting homocysteine subcutaneously (0.03 μmol/g of body weight) twice a day, from the 30th to the 60th postpartum day. Controls received saline in the same volumes. Using this model, we evaluated the effect of chronic administration of homocysteine on redox status in the blood and cerebral cortex of adult rats. Reactive oxygen species and thiobarbituric acid reactive substances were significantly increased in the plasma and cerebral cortex, while nitrite levels were reduced in the cerebral cortex, but not in the plasma, of rats subjected to chronic mild hyperhomocysteinemia. Homocysteine was also seen to disrupt enzymatic and non-enzymatic antioxidant defenses in the blood and cerebral cortex of rats. Since experimental animal models are useful for understanding the pathophysiology of human diseases, the present model of mild hyperhomocysteinemia may be useful for the investigation of additional mechanisms involved in tissue alterations caused by homocysteine.     

Hyperhomocysteinemia increases damage on brain slices exposed to in vitro model of oxygen and glucose deprivation: prevention by folic acid

In the present study we evaluate the effects of homocysteine on cellular damage using hippocampal slices from Wistar rats exposed to oxygen and glucose deprivation (OGD, followed by reoxygenation), an in vitro model of hypoxic-ischemic events. For chronic treatment, we induced elevated levels of homocysteine in blood (500 microM), comparable to those of human homocystinuria, and in brain (60 nmol/g wet tissue) of young rats by subcutaneous injections of homocysteine (0.3-0.6 micromol/g of body weight), twice a day with 8 h intervals, from the 6 th to the 28 th postpartum day and controls received saline. Rats were sacrificed 1, 3 or 12 h after the last injection. For acute treatment, 29-day-old rats received one single injection of homocysteine (0.6 micromol homocysteine/g body weight) or saline and were sacrificed 1h later. In another set of experiments rats were pretreated with Vitamins E (40 mg/kg) and C (100 mg/kg) or folic acid (5 mg/kg) during 1 week; 12 h after the last administration they received a single injection of homocysteine or saline and were sacrificed 1 h later. Results showed that both chronic (1 h after homocysteine administration) and acute hyperhomocysteinemia increased the cellular damage measured by LDH released to de incubation medium, suggesting an increase of tissue damage caused by OGD. Pretreatment with folic acid completely prevented the damage caused by acute hyperhomocysteinemia, whereas Vitamin E just partially prevented such effect. These findings may be relevant to explain, at least in part, the higher susceptibility of hyperhomocysteinemic patients to be susceptible to ischemic events and point to a possible preventive treatment.     

血浆同型半胱氨酸与脑梗死的相关性研究

目的探讨血浆同型半胱氨酸水平对脑梗死的影响。方法采用高效液相色谱仪HPLC-FD法检测40例急性脑梗死患者的血浆Hcy,采用离子捕获法测定患者叶酸（Fol）、维生素B12（VitB12）等指标,与40名健康对照者比较。结果 脑梗死组血浆Hcy水平和甘油三酯（TG）明显高于对照组,而Fol及VitB12水平则低于对照组,差异有统计学意义（P〈0.05）。高Hcy血症与脑梗死相关,相对危险度OR为8.921（95%CI 2.16～30.32）,脑梗死组和对照组血浆Hcy水平与血Fol、VitB12水平均呈显著负相关。结论 高同型半胱氨酸血症是脑梗死的独立危险因素。     

慢性肾衰竭患者同型半胱氨酸与脑卒中的关系

目的　研究慢性肾衰竭 (CRF)患者同型半胱氨酸 (Hcy)水平与脑卒中的关系。方法　采用荧光偏振免疫法 (FDIA )测定 97例 CRF患者 (其中 30例并发脑卒中 )和 35例健康对照组血浆总 Hcy水平 ,并对结果进行统计学处理、分析。结果　 CRF患者血浆总 Hcy水平明显高于健康对照组 ,有显著性差异 (P<0 .0 0 1) ,其中并发脑卒中组血浆总 Hcy水平明显高于未并发脑卒中组 ,有显著性差异 (P<0 .0 5 ) ;CRF患者血浆 Hcy水平分别与叶酸、维生素 B1 2 呈负相关。结论　慢性肾衰竭患者普遍存在高同型半胱氨酸血症 ,并可能参与了脑卒中的发生过程 ,临床应监测 CRF患者的血浆总 Hcy水平 ,并对高 Hcy血症者给予相应的治疗 ,以防止 CRF患者并发脑卒中     

同型半胱氨酸与兔脑动脉损伤的关系及维生素B6、B12、叶酸对其预防作用的探讨

目的探讨高蛋氨酸(Met)喂饲兔引发高同型半胱氨酸(Hcy)血症与脑动脉损伤的关系,同时观察补充VitB6、VitB12、叶酸对血Hcy水平和动脉损伤的影响.方法采用纯种雄性新西兰兔26只,分为三组对照组、高蛋氨酸组、干预组,分别喂以普通兔饲料每只200g/d、普通饲料添加0.5%Met、普通饲料每天每只兔添加0.5%Met、叶酸2.5mg、VitB6 10mg、VitB12 200mg,喂养6个月,测定血浆总Hcy(tHcy),光镜检测脑动脉组织学改变.结果实验前血浆tHcy浓度三组间无明显差异,实验后断食2 h和7 h血tHcy浓度高Met组明显高于对照组(P＜0.01),而干预组血tHcy浓度明显低于高Met组(P＜0.01),但仍高于对照组.光镜组织学检测发现高Met组和干预组脑动脉可见内皮细胞坏死、脱落、溃疡形成,附壁血栓,中膜平滑肌散乱疏松.结论高Met引发高Hcy血症对脑动脉有损伤,且VitB6、VitB12、叶酸的补充可以降低高Met引发的高Hcy浓度的水平.     

血浆同型半胱氨酸与颅内动脉瘤的关系

目的 探讨血浆同型半胱氨酸(Hcy)、血清叶酸、维生素B12水平与颅内动脉瘤的关系.方法 采用化学发光法检测80例颅内动脉瘤患者和60例对照者血浆Hcy、血清叶酸、维生素B12水平,相关危险因索用logistic回归分析.结果 颅内动脉瘤组平均血浆Hcy水平明显高于对照组(P=0.005),两组中血浆Hcy升高分别有38例(48%)和9例(15%)(X2=16.239,P＜0.001);颅内动脉瘤组平均血清叶酸、维生素B12水平明显低于对照组(P=0.01;P=0.005);颅内动脉瘤患者血浆Hcy水平与血清叶酸、维生素B12水平呈负相关(P＜0.05).多因素logistic回归分析显示:血浆Hcy是颅内动脉瘤发病的独立危险因素,比值比(OR)=3.961[P=0.019,95%可信区间(CI):1.255～12.500].结论 高Hcy血症与颅内动脉瘤发病有密切关系,可能是颅内动脉瘤发病的一个独立危险因素;血浆Hcy水平升高可能与血清叶酸、维生素B12水平降低有关.