槲皮黄酮对酒精性肝损伤大鼠高同型半胱氨酸血症及氧化应激的作用

目的探讨槲皮黄酮对酒精性肝损伤大鼠高同型半胱氨酸血症(HHcy)及氧化应激的作用。方法将30只大鼠随机分为正常对照组、模型组、低剂量槲皮黄酮治疗组、中剂量槲皮黄酮治疗组、高剂量槲皮黄酮治疗组,每组6只。用酒精+0.5 mL鱼油灌胃诱导酒精性肝损伤模型,造模3周后,治疗组大鼠分别给予4、2、1 g/kg槲皮黄酮灌胃,7周后麻醉处死大鼠,测定血浆总同型半胱氨酸(tHcy)浓度及血清丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、白蛋白(Alb)、白/球蛋白比值(A/G)、肝匀浆丙二醛(MDA)、超氧化物歧化酶(SOD)和还原型谷胱甘肽(GSH)表达水平,并对肝脏病理组织进行检测。结果模型组大鼠tHcy、ALT、AST、MDA的表达水平高于正常对照组,而SOD、GSH含量低于对照组,差异均有统计学意义(P<0.05);治疗后,槲皮黄酮治疗组大鼠tHcy、ALT、AST、MDA均低于模型组(P<0.05),而SOD、GSH含量高于模型组(P<0.05),并呈浓度依赖性。组织病理学检测显示,模型大鼠出现肝细胞脂肪变性、点状坏死,伴随炎性细胞浸润,槲皮黄酮治疗后,点状坏死和炎性细胞浸润消失。结论槲皮黄酮可改善酒精性肝损伤,其作用机制可能与降低高同型半胱氨酸水平及氧化应激有关。     

高同型半胱氨酸血症对帕金森病的影响

目的研究高同型半胱氨酸血症对帕金森病的发病与药物治疗的影响。方法选择正常老年组30例和未治疗帕金森病(PD)患者组30例,应用高效液相色谱法测定血浆同型半胱氨酸(hcy)水平。选择治疗中的PD患者60例,分为治疗组(应用美多巴)30例和对照组30例(应用其他抗震颤麻痹药物),同样方法测定其血浆中hcy水平。结果未治疗PD组、治疗组和对照组的hcy水平分别为:18.79±2.14、21.30±3.57和19.82±2.80,与正常老年组(12.31±1.26)比较显著升高(P<0.05),治疗组与未治疗PD组、对照组比较hcy水平无明显差异。结论高同型半胱氨酸血症是PD的危险因素,但对PD的治疗无明显影响。     

高同型半胱氨酸血症对下肢动脉弹性功能的影响

目的 研究高同型半胱氨酸血症患者下肢动脉弹性功能的变化。方法应用科林BP-203RPEⅡ（VP—1000）动脉弹性测定仪检测13例高同型半胱氨酸血症患者和15例健康志愿者下肢动脉弹性,即踝肱脉搏波传导速度（baPWV）和踝臂指数（ABI）。结果高同型半胱氨酸患者与对照组比较,高同型半胱氨酸患者的baPWV[（1874±106）cm／svs（1200±105）cm／s,P〈0．05）】明显升高,动脉僵硬度升高,下肢动脉弹性明显下降,踝臂指数（ABI）两组间差异无显著性。结论高同型半胱氨酸血症可致下肢血管动脉弹性下降,是引起动脉硬化的危险因素。     

不同性别原发性高血压患者同型半胱氨酸水平、高同型半胱氨酸血症研究

目的研究不同性别原发性高血压患者血浆同型半胱氨酸（Hcy）水平、高同型半胱氨酸血症（hHcy）。方法 482例原发性高血压患者,测定其血浆同型半胱氨酸水平及其他健康指标,对其中男357例,女125例的血清同型半胱氨酸水平及高同型半胱氨酸血症的关系进行统计学分析。结果 1原发性高血压患者男性的同型半胱氨酸水平（13.29±5.81）μmol/L显著高于女性（9.68±4.71）μmol/L（P〈0.001）,调整年龄、体质量指数（BMI）、收缩压、舒张压等因素后,男性同型半胱氨酸水平显著高于女性（P〈0.001）。2高同型半胱氨酸血症的发生率男性73.1%高于女性29.6%（P〈0.001）,调整年龄、BMI、收缩压、舒张压等因素后,男性高同型半胱氨酸血症发生率显著高于女性（P〈0.001）。结论原发性高血压患者血浆同型半胱氨酸水平、高同型半胱氨酸血症与性别存在相关性。     

大蒜素对高同型半胱氨酸血症大鼠自由基代谢的影响

目的:从自由基代谢方面观察大蒜素对高同型半胱氨酸血症的影响。方法:Wistar雄性大鼠分为大蒜素高剂量组、大蒜素低剂量组、叶酸对照组、模型对照组和空白对照组,饲养6周,腹腔静脉取血,测定血清同型半胱氨酸和SOD、MDA,数据进行统计学分析。结果:模型对照组在6周时血浆同型半胱氨酸水平高于空白对照组和大蒜素高、低剂量组;模型对照组和叶酸对照组的血清超氧化物岐化酶(SOD)水平低于空白对照组(P<0.05),大蒜素高剂量组和大蒜素低剂量组的血清SOD水平明显高于模型对照组(P<0.05),叶酸对照组的血清SOD水平与模型对照组差异无显著性(P>0.05);模型对照组和叶酸对照组的血清丙二醛(MDA)水平显著高于空白对照组(P<0.05),大蒜素高剂量组和大蒜素低剂量组的血清MDA水平明显低于模型对照组(P<0.05),大蒜素高剂量组和大蒜素低剂量组的血清MDA水平也明显低于叶酸对照组(P<0.05),叶酸对照组的血清MDA水平与模型对照组比较差异无显著性(P>0.05)。结论:大蒜素能明显降低高同型半胱氨酸血症大鼠血中的同型半胱氨酸水平,并升高高同型半胱氨酸血症大鼠血清SOD活性,降低高同型半胱氨酸血症大鼠血清M...     

高同型半胱氨酸血症与动脉粥样硬化的关系

近年血浆同型半胱氨酸(homocysteine,Hcy)的研究受到广泛关注。除极少数的研究,几乎发表的文章都指出高Hcy是动脉粥样硬化性疾病和静脉血栓形成的独立危险因素[1],与冠心病、脑血管疾病、外周血管疾病和静脉血栓的发生和发展相关。可经补充叶酸、维生素B12、维生素B6而纠正。现     

高同型半胱氨酸血症与缺血性脑卒中关系

目的　分析高同型半胱氨酸 (Hcy)血症与缺血性脑卒中的关系。方法　应用高压液相色谱法(HPLC)对 35例缺血性脑卒中组患者和 35例对照组中的健康体检者进行血浆Hcy测定。结果　缺血性脑卒中患者的平均血浆Hcy(18. 9±6. 8)μmol/L高于对照组(11. 4±4. 1)μmol/L,且具有显著性差异(P<0. 001)。结论　高同型半胱氨酸血症是缺血性脑卒中的独立危险因子,应该给予重视及治疗。     

高同型半胱氨酸血症治疗药物研究进展

高同型半胱氨酸血症是心脑血管疾病的一个独立的、重要的危险因素.本文综述近年高同型半胱氨酸血症治疗药物研究进展,重点介绍药物的临床应用以及活性化合物和复合制剂的开发.     

高同型半胱氨酸血症对脑梗死发病率的影响

目的研究探讨高同型半胱氨酸血症对脑梗死发病率的影响。方法对2011年5月至2012年5月来我院治疗的脑梗死患者158例进行回顾性分析,同期门诊体检的健康人49例作为对照组,探讨各脑梗死危险因素对脑梗发病的影响。结果研究组各危险因素水平显著高于对照组（P〈0.05）,且高同型半胱氨酸与其他危险因子无相关。结论高同型半胱氨酸血症同其他传统脑梗死危险因素皆对脑梗死的发病率有显著影响,且为独立危险因子。     

高同型半胱氨酸血症对大鼠股骨骨折骨愈合的影响及干预

目的：探讨高同型半胱氨酸血症（Hhey）对大鼠股骨骨折愈合的影响及维生素B12干预后的结果。方法：36只SD大鼠随机分为对照组、Hhcy组、干预组,并制作股骨骨折模型,评价大鼠股骨骨折愈合水平。结果：①Hhcy组大鼠总同型半胱氨酸tHey（21．56±5．32）μmol／L高于对照组（12．72±3．02）μmol／L（P〈0．05）,干预组tHey水平（13．76±6．34）μmol／L与对照组（12．72±3．02）μmol／L比较,差异无统计学意义（P〉0．05）;②大鼠股骨密度（BMD）Hhcy组（0．175±0．010）g／cm^2低于对照组（0．285±0．007）g／cm^2（P〈0．05）,干预组（0．279±0．015）g／cm^2与对照组（0．285±0．007）g／cm^2比较,差异无统计学意义（P〉0．05）。结论：高同型半胱氨酸血症影响骨折愈合,应用维生素B12可以减轻Hhcy对大鼠骨折愈合的影响。     

Investigation of oxidant stress and vasodepression to glyceryl trinitrate in the obese Zucker rat in vivo

1. We examined the relationship between oxidant stress and the vasodepressor activity of glyceryl trinitrate (GTN) in vivo, including rapid GTN tolerance development, in 13-week old obese and age-matched lean Zucker rats which had been maintained for 4 weeks on either control diet or diets enriched with the lipophilic, chain-breaking antioxidants vitamin E (0.5% w w⁻¹) or probucol (0.5% w w⁻¹) or the superoxide anion scavenger tiron (1% w v⁻¹ in drinking water).
2. The basal plasma level of the isoprostane 8-epi-PGF_2α, an in vivo marker of lipid peroxidation, was elevated by approximately 5 fold in the obese Zucker rat and markedly reduced by dietary lipophilic antioxidants and depressed by dietary tiron.
3. Vasodepression to bolus does GTN (0.1–100 μg kg⁻¹ i.v.), but not endothelium-dependent vasodepression to bolus dose acetylcholine (ACh, 0.02–2.0 μg kg⁻¹ i.v.), was impaired in obese animals and completely restored by dietary antioxidants.
4. Nitrate tolerance developed in vivo during a 1 h infusion of GTN (40 μg kg⁻¹ min⁻¹ i.v.) appeared more severe in obese animals. However, rapid nitrate tolerance was not affected by dietary antioxidants in either the obese or lean Zucker rat.
5. We therefore provide evidence that elevated oxidant stress in the obese Zucker rat is associated with an impairment in nitrate vasodepressor activity. However, our data are not consistent with either a role for oxidant stress in rapid nitrate tolerance development in the anaesthetized Zucker rat or the aggravation of this tolerance by pre-existing oxidant stress.

     

Effect of hyperhomocysteinemia on cardiovascular risk factors and initiation of atherosclerosis in Wistar rats

Hyperhomocysteinemia is considered an independent risk factor for atherosclerosis. The present study was designed to assess the effect of high level of serum homocysteine on other cardiovascular risk factors and markers in rats and to study its mode of action in initiating atherosclerosis. To address this issue, four different doses of methionine (0.1 g/kg, 0.25 g/kg, 0.5 g/kg, 1 g/kg) were orally administered to four groups (Group II, III, IV, V respectively) of rats (6 rats in each group) for a period of 8 weeks to get different level of homocysteine in serum. Group I was administered with saline and served as control. Our results revealed that the level of Total cholesterol, Triglyceride, and Oxidized low-density lipoproteins increased significantly with the increase in the level of serum homocysteine. The levels of Resistin, C-reactive protein and cysteinyl-leukotrienes were found to be significantly high in Group IV (P<0.001 vs Group I) and Group V (P<0.001 vs Group I) at 8 weeks. Total antioxidant capacity and nitrite/nitrate level in serum showed negative correlation with the increased dose of methionine. The mRNA expression and the enzyme activity of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase significantly increased only in livers of rats of Group V. Furthermore, high mRNA expression of P2 receptors and caveolin were found in aorta of rats administered with high dose of methionine (Group IV and V at 8 weeks). Data obtained from in-vitro effect of homocysteine on isolated aortic arch also showed induction in P2 receptors and caveolin with the increase in the concentration of homocysteine. These findings collectively suggest that hyperhomocysteinemia initiates atherosclerosis by modulating the cholesterol biosynthesis and by significantly inducing the level of other cardiovascular risk factors and markers, which play important role in initiating atherosclerosis.     

高同型半胱氨酸血症对慢性应激模型大鼠行为学及神经生化的影响

目的研究高同型半胱氨酸血症(Hhcy)对慢性不可预见应激模型大鼠行为学、神经递质及神经营养因子水平的影响。方法以高蛋氨酸饮食喂养大鼠制作Hhcy模型(Hhcy组,12只);另选24只大鼠,均分为普食组和对照组,均给予普通饮食喂养;Hhcy组与普食组给予慢性不可预见性刺激。比较三组的学习记忆能力、海马组织5-羟色胺(5-HT)和5-羟基吲哚乙酸(5-HIAA)含量以及脑脊液中神经营养因子(BDNF)水平。结果水迷宫实验中,Hhcy组目的象限停留时间比普食组短(P<0.05);Hhcy组海马5-HIAA含量和脑脊液中BDNF含量均较普食组低(P<0.05)。结论Hhcy可致慢性应激模型大鼠学习记忆能力的下降,加重神经递质及生长因子水平的异常,可能为抑郁症的危险因素之一。     

上消化道急性应激性黏膜病变出血的急诊内镜诊断和治疗

目的探讨上消化道急性应激性黏膜病变出血患者的急诊内镜诊断和治疗。方法对上消化道急性应激性黏膜病变出血患者60例进行急诊内镜检查,并行内镜下治疗及其他治疗的资料进行回顾性分析。结果60例患者内镜下病变表现为4种类型,其中充血水肿型36例、急性溃疡型22例、出血糜烂型20例、坏死剥脱型12例(有的各型并存)。单纯内镜下止血14例全部成功,内镜下止血加静脉给药止血20例亦全部成功;内镜下止血+胃管注药+静脉给药止血18例、成功15例;内镜下止血+胃管注药+静脉给药+手术止血8例、成功5例;有6例重症患者虽经内、外科综合治疗仍然病死。结论急诊内镜不仅是上消化道急性应激性黏膜病变出血准确可靠的诊断手段,而且也是一种快速有效的治疗方法。     

Phenolic fractions from Trifolium pallidum and Trifolium scabrum aerial parts in human plasma protect against changes induced by hyperhomocysteinemia in vitro

Elevated concentration of homocysteine (Hcy) in human plasma, defined as hyperhomocysteinemia has been correlated with some diseases, such as cardiovascular, neurodegenerative, and kidney disorders. Homocysteine occurs in human plasma in several forms, including the most reactive form of Hcy – its cyclic thioester – homocysteine thiolactone (HTL), which represents up to 0.29% of plasma total Hcy. It is suggested that Hcy and HTL may also act as oxidants, but various polyphenolic antioxidants are able to inhibit the oxidative damage induced by Hcy or HTL. The aim of our present study was to investigate in vitro oxidative changes in human plasma induced by the model of hyperhomocysteinemia in the presence of the phenolic fractions from selected clovers (Trifolium pallidum and Trifolium scabrum aerial parts). Hyperhomocysteinemia was stimulated by a reduced form of Hcy (final dose 100 μM) or HTL (final dose 1 μM). The aim of our study was also to explain the effect of the phenolic fractions on the coagulation activity of human plasma treated with Hcy and its thiolactone. Tested phenolic fractions significantly inhibited the oxidative stress (measured by the total antioxidant level – TAS) in plasma treated with Hcy or HTL. The phenolic fractions from T. pallidum and T. scabrum also caused a distinct reduction of plasma lipid peroxidation (measured by the level of thiobarbituric acid reactive substance) induced by the model of hyperhomocysteinemia. Moreover, tested fractions modulated the coagulation properties of plasma treated with homocysteine and its thiolactone. It seems that antioxidative activities of the phenolic fractions from T. pallidum and T. scabrum aerial parts may be responsible for their medicinal properties during hyperhomocysteinemia.     

The role of oxidant stress in angiotensin II-mediated contraction of human resistance arteries in the state of health and the presence of cardiovascular disease

BACKGROUND: Angiotensin II is a powerful vasoconstrictor and regulator of cardiovascular growth. Also, it increases formation of reactive oxygen species and contributes to vascular dysfunction. We investigated the role of oxidant stress in contraction of human resistance arteries to angiotensin II, in health and in the presence of cardiovascular disease. METHODS AND PATIENTS: Studies of isometric contraction to angiotensin II, using human resistance arteries from healthy volunteers and patients, undergoing cardiac revascularization surgery, were performed by the broad-spectrum antioxidant agent vitamin C and superoxide dismutase mimetic TEMPOL. In the presence of vitamin C, the potency and the maximum contractile response were reduced in both patients and healthy volunteers. Addition of TEMPOL caused a decrease in angiotensin II-induced contraction only in the patients' group. CONCLUSIONS: Our studies provide evidence for the role of oxidant stress in the contractile response of human resistance arteries to angiotensin II. In patients with cardiovascular disease, the superoxide anion may be the major species involved. In healthy subjects, other reactive oxygen species and the redox-independent vasoconstrictor action of angiotensin II predominate. CONDENSED ABSTRACT: Increased formation of reactive oxygen species, due to angiotensin II, contributes to vascular dysfunction. We determined the oxidative reactivity of human resistance arteries to angiotensin II in healthy subjects and patients, undergoing cardiac revascularization surgery, using the broad-spectrum antioxidant agent, vitamin C, and superoxide dismutase mimetic, TEMPOL. There was a large decrease in potency and maximum of angiotensin II-induced contractile response noted in both groups with the former, while the latter reduced contraction only in the patients' group. Superoxide anion may play a major role in angiotensin II contractions of human resistance arteries in the presence of cardiovascular disease. In healthy subjects, other reactive species and the redox-independent pathways predominate.     

肥胖者吸烟对动脉僵硬度与氧化应激的影响

目的观察肥胖者吸烟对动脉僵硬度及氧化应激的影响。方法选取大学在校男生85人,按照BMI或腰围大小分为2组,对照组41人,实验组44人,实验组进行吸烟干预25d,对照组无任何干预,测定对照组及实验组吸烟前、后每位受试者动脉僵硬度、血浆谷胱甘肽、丙二醛、尿酸含量并进行对比。结果实验组吸烟前与对照组比较,动脉僵硬度（1．78±0．26VS1．97±0．38,P〈0．05）及血浆丙二醛[（3．88±1．13）μmol／LVS（4．32±1．56）μmol／L,P〈0．05]、尿酸含量[（295±43）μmol／LVS（361±57）μmol／L,P〈0．05]显著增高;实验组吸烟后与对照组及实验组吸烟前比较,动脉顺应性显著下降[（1．54±0．32）ml／mmHgVS（1．97±0．38）ml／mmHg,P〈0．01;（1．54±0．32）ml／mmHgVS（1．78±0．26）ml／mmHg,P〈0．05],与对照组比较,实验组吸烟前后丙二醛尿酸含量则显著上升[丙二醛：（4．32±1．56）vs（3．88±1．13）,（4．77±1．07）vs（3．88±1．13）;尿酸：（361±57）VS（295±43）,（472±39）μmol／L vs（295±43）μmol／L,P〈0．01或P〈0．05]。结论氧化应激反应产物丙二醛、尿酸含量的增高,说明机体氧化．抗氧化机制失衡有助于动脉僵硬度和动脉顺应性发生改变,增加心血管疾病的患病风险,而肥胖者吸烟更具有患病的高危性。     

Protective effect of nimesulide against hepatic ischemia/reperfusion injury in rats: Effects on oxidant/antioxidants,DNA mutation and COX-1/COX-2 levels

BackgroundNimesulide is a pharmacological agent and selective COX-2 inhibitor. It has anti-inflammatory, analgesic and antipyretic properties. The purpose of this study was to investigate the effect of nimesulide on oxidant/antioxidant, DNA mutation and COX-1/COX-2 activities in rat liver tissue with induced ischemia/reperfusion (I/R).MethodsBefore the experiment, rats were divided into four groups; liver ischemia/reperfusion (LIR), 50 mg/kg nimesulide + liver ischemia/reperfusion (NLIR50), 100 mg/kg nimesulide + liver ischemia/reperfusion (NLIR100) and a control group to be given a sham operation (SG). Malondialdehyde (MDA), total glutathione (GSH) levels and myeloperoxidase (MPO), COX-1/COX-2 enzyme activities and DNA damage product level results from liver tissues and serum AST and ALT levels were determined. The data obtained were compared with the results from the liver ischemia/reperfusion and sham operation groups.ResultsMDA levels, MPO and COX-2 activities and products of DNA injury were significantly lower in the groups given nimesulide, and particularly the NLIR100 group, compared to the LIR group (p < 0.05), while tGSH levels were significantly higher (p < 0.05). There was no significant difference between the NLIR50 and NLIR100 groups and the LIR group in terms of COX-1 levels (p > 0.05). AST and ALT levels were significantly lower in the other groups compared to the LIR group (p < 0.05).ConclusionsNimesulide at 100 mg/kg prevented oxidative liver damage induced with I/R significantly better than at a dose of 50 mg/kg. These experimental findings indicate that nimesulide may be useful in the treatment of hepatic I/R damage.