2型糖尿病伴高血压患者血小板5-HT与心脑血管并发症的关系

目的探讨糖尿病伴高血压患者血小板5-羟色胺(5-HT)与心血管并发症的关系.方法应用磷光-荧光分光光度法测定59例2型糖尿病的患者、57例糖尿病伴高血压患者和35名正常对照组的血小板5-HT和血浆5-羟吲哚类物质(5-HIS)水平.结果2型糖尿病组血小板5-HT(514.9±153.7)ng/109pt明显低于正常对照组(618.4±194.1)ng/109pt(P＜0.05),2型糖尿病伴高血压组血小板5-HT(323.1±180.4)ng/109pt明显低于2型糖尿病组(P＜0.001)及正常对照组(P＜0.001).糖尿病患者中有心脑血管并发症者5-HT水平比无心脑血管并发症患者降低更为明显.结论糖尿病伴高血压患者血小板5-HT的释放使血压升高并加重心血管危险因素.     

2型糖尿病伴高血压患者血小板5-HT与心脑血管并发症的关系

目的探讨糖尿病伴高血压患者血小板5羟色胺(5HT)与心血管并发症的关系。方法应用磷光-荧光分光光度法测定59例2型糖尿病的患者、57例糖尿病伴高血压患者和35名正常对照组的血小板5-HT和血浆5羟吲哚类物质(5-HIS)水平。结果2型糖尿病组血小板5-HT(514.9±153.7)ng/109pt明显低于正常对照组(618.4±194.1)ng/109pt(P<0.05),2型糖尿病伴高血压组血小板5HT(323.1±180.4)ng/109pt明显低于2型糖尿病组(P<0.001)及正常对照组(P<0.001)。糖尿病患者中有心脑血管并发症者5-HT水平比无心脑血管并发症患者降低更为明显。结论糖尿病伴高血压患者血小板5-HT的释放使血压升高并加重心血管危险因素。     

2型糖尿病患者外周血淋巴细胞G蛋白偶联受体激酶2基因表达升高

目的探讨糖尿病对G蛋白偶联受体激酶2（GRK-2）基因的影响及其机制。方法56例40-65岁非高血压2型糖尿病（T2DM）患者为T2DM组,以年龄、性别相匹配的高血压糖尿病患者46例（HT-DM组）和体检健康者29例（NC组）为对照组,提取外周血淋巴细胞RNA,通过RT-PCR半定量检测GRK-2 mRNA表达。结果与HT-DM组相似,T2DM组外周血淋巴细胞GRK-2 mRNA表达水平较NC组明显增加（P〈0.05）。Pearson线性相关分析提示T2DM组患者GRK-2基因表达水平升高与PG、HbA1c、糖尿病病程、年龄、TC水平正相关（P〈0.05）。结论T2DM患者外周血淋巴细胞GRK-2基因表达升高,血糖升高可能是其重要原因。     

2型糖尿病家系非糖尿病一级亲属代谢综合征及相关组分患病率的临床研究

目的 了解T2DM家系中非糖尿病一级亲属MS及主要组分的患病率. 方法 选取恩施地区符合条件的128个土家族T2DM家系行OGTT,去除家系组中二级亲属、配偶组中有糖尿病家族史和T2DM患者,将剩余成员分为T2DM组322例、非糖尿病一级亲属（FDR）组298例和非糖尿病且无糖尿病家族史的配偶（NC）组102名.比较各组人体测量学参数、血糖、BP、血脂、胰岛素等指标的差别,及MS和主要组分的患病率. 结果 FDR组肥胖、腹型肥胖、IGR、高血压、高TG血症、低HDL-C血症、MS（MCEP-ATPⅢ标准）和MS（IDF标准）的患病率均高于NC组（P＜0.05或P＜0.01）,但低于T2DM组（P＜0.05或P＜0.01）. 结论 T2DM及相关的代谢异常如肥胖、高血压、脂代谢异常等存在明显的家族聚集性.T2DM家系中非糖尿病一级亲属已表现出不同程度的代谢异常.     

冠心病合并2型糖尿病患者的临床及冠脉造影特点

目的 探讨冠心病合并2型糖尿病（T2DM）患者的临床表现及冠状动脉病变的特点.方法 137例经冠脉造影（CAG）确诊为冠心病的患者按是否合并2型糖尿病分为糖尿病组（T2DM组）及非糖尿病组（NDM组）,对两组患者的一般情况、临床资料、血清学指标及CAG结果进行比较.结果 T2DM组的高血压、高血糖症及急性冠脉综合征的发生率明显高于NDM组,总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）明显升高（P＜0.05）;T2DM组多支病变、弥漫性病变、C型病变均高于NDM组（P＜0.05）.两组患者年龄、性别比例、吸烟史、高密度脂蛋白胆固醇（HDL-C）、肌酐（Cr）、尿酸（UA）比较差异无统计学意义（P＞0.05）.结论 冠心病合并2型糖尿病患者的高血压发生率、TC、TG、LDL-C均高于无糖尿病的冠心病患者,冠状动脉的病变也比后者严重.     

糖尿病对老年高血压患者心脏结构的影响

目的探讨糖尿病对老年高血压患者心脏结构的影响。方法将351例60岁以上的住院患者分为3组,即单纯高血压（EH）组149例,高血压合并2型糖尿病（T2DM）组129例和对照组73例,依据超声心动图结果评价心脏的结构。结果与单纯EH组比较,EH＋T2DM组的舒张末期左心室内径（LVD）、左室质量（LVM）、左室质量指数（LVMI）明显升高（P〈0．01）。EH＋T2DM组、EH组和对照组左室肥厚（LVH）的发生率分别为48．1％、34．9％和17．8％（P〈0．05／〈0．01）。EH＋T2DM组正常左室几何构型（NG）的比例低于EH组和对照组（44．2％vs56．4％vs82．2％．P〈0．05和〈0．01）;EH＋T2DM组离心性肥厚（ECH）的比例高于EH组和对照组（43．4％vs27．5％vs15％．P〈0．01）,三组间向心性肥厚（CCH）和向心性重构（CCR）的比例无显著性差异。结论糖尿病对老年高血压患者心脏结构有一定影响,高血糖可加重老年高血压患者心脏结构的异常。     

5-羟色胺2A受体基因多态性与糖尿病血管舒张功能的关联

用PCR-RFLP方法检测79例T2DM患者与84例健康正常人的5-HT2AR基因1438A/G多态性,用彩色多谱勒超声测定肱动脉反应性充血后以及含服硝酸甘油后血管内径的变化。T2DM组GG型者血清5-HT水平显著升高（P〈0.01）,NO水平显著降低（P〈0.05）,内皮依赖性血管舒张功能减弱（P〈0.05）。结果说明5-HT2AR基因1438位碱基纯合突变可能与T2DM血管舒张功能减弱有关。     

2型糖尿病合并外周血管病变相关危险因素探讨

目的探讨2型糖尿病（T2DM）患者发生外周血管病变（PVD）的危险因素。方法选取180例T2型DM患者,其中合并PVD80例,无PVD100例,检测相关临床指标。结果T2DM合并PVD组糖尿病病程、血清肌酐、总胆固醇、高密度脂蛋白胆固醇、高血压、脑梗死史、高敏C反应蛋白（hsC-RP）和白细胞介素6（IL-6）水平显著高于无PVD组。多因素回归分析显示hsC-RP和糖尿病病程与T2DM并发PVD正相关。结论hsC-RP是促使T2DM并发PVD的独立危险因素。     

糖尿病患者合并高血压对降压药物的选择和应用

糖尿病（DM）和高血压都是心血管疾病的独立危险因素，两者合并存在将使心血管疾病的死亡率增加2～8倍。DM人群中高血压的患病率是普通人群的1．5～3倍。2005年《中国高血压防治指南》（下称《指南》）中指出，我国高血压在DM人群中的患病率大约是40％～55％。而在高血压人群中，DM的患病率是正常血压人群的2，5倍。2型糖尿病（T2DM）患者50％以上的死亡率均由心血管疾病和肾脏疾病所致，而T2DM患者75％以上的心血管和肾脏并发症都与合并高血压密切相关。T1DM患者高血压的发生机制与T2DM有明显差别，高血压发生于疾病诊断后多年，可能继发于糖尿病肾病（DN）。DM患者的降压药物选择是否合理不仅以血压下降水平为标准，还要兼顾合并症治疗、功能受损器官的保护及对糖脂代谢的影响等。     

高血压合并2型糖尿病患者内皮功能损伤及靶器官损害的变化

目的探讨高血压合并2型糖尿病患者内皮功能损伤及靶器官损害的变化。方法根据糖尿病的诊断标准将98例高血压患者分为原发性高血压组（EH组）48例,EH合并2型糖尿病组（EH＋T2DM组）50例;另取健康体检者30例作为对照组。采用酶联免疫吸附双抗体夹心法测定各组血浆内皮损伤标志物血管性假血友病因子（vWF）,彩色多普勒超声测定颈动脉内膜中层厚度（IMT）、左室质量指数（LVM I）、并测定24 h尿微量白蛋白（mALB）。结果EH＋T2DM组、EH组、对照组vWF、LVM、IIMT、24 h尿mALB均依次增高,三组间比较差异具有统计学意义（P〈0.05或〈0.01）。左室肥厚（LVH）、颈动脉斑块发生率：EH＋T2DM组〉EH组〉对照组,三组比较均有统计学意义（P均〈0.05）。结论T2DM加重了EH病患者内皮功能损伤及靶器官的损害。     

5-羟色胺与2型糖尿病下肢血管病变程度的关联

应用彩色多普勒检杳98例2型糖尿病患者的下肢动脉硬化程度,高效液相色谱一紫外光检测法测定血清5-羟色胺水平.结果 提示病变组5-羟色胺显著高于无病变组(P<0.01),重度病变组5-羟色胺显著高于轻、中度病变组(P<0.01).     

Down-regulation of the serotonin transporter in hyperreactive platelets counteracts the pro-thrombotic effect of serotonin

An elevated plasma concentration of serotonin ([5-HT]) is a common feature of cardiovascular disease often associated with enhanced platelet activation and thrombosis. Whether elevated in vivo plasma 5-HT per se represents an independent risk factor for platelet hyperreactivity or only is an epiphenomenon of cardiovascular disease is poorly understood. We examined in vitro and in vivo platelet function following a 24h elevation of plasma [5-HT] in mice. In vivo administration of 5-HT using osmotic minipumps increased plasma [5-HT] in treated mice compared to control mice instrumented with saline loaded pumps. 5-HT infusion did not increase systolic blood pressure, but markers of platelet activation including P-selectin and (PE)Jon/A staining were increased and these findings coincided with the enhanced aggregation of isolated platelets in response to type I fibrillar collagen. Tail bleeding times and the time to occlusion following chemical damage to the carotid artery were shortened in 5-HT-infused mice. 5-HT-infused mice were treated with paroxetine (Prx) to block 5-HT uptake via the serotonin transporter (SERT). Prx lowered platelet [5-HT] and attenuated platelet activation and aggregation. These results and our biochemical indices of enhanced 5-HT intracellular signaling in the platelets of 5-HT-infused mice reveal a mechanistic link between elevated plasma [5-HT], abnormal intracellular 5-HT signaling and accentuated platelet aggregation. Although a down-regulation of the serotonin transporter (SERT) on the platelet surface may counteract the pro-thrombotic influence of elevated plasma [5HT], this compensatory mechanism may fail to prevent the increased thrombotic risk caused by elevated plasma [5-HT].     

Reduced platelet serotonin content in rabbits with dietary hypercholesterolemia.

Serotonin [5-hydroxytryptamine (5-HT)] has been implicated in platelet activation and vasoconstriction, two processes that contribute to arterial thrombosis in atherosclerotic diseases. In the present study, Japanese White rabbits fed 1% cholesterol for 5 weeks were used to investigate the response of hypercholesterolemic vascular arteries and platelets to 5-HT. Contractions of the thoracic aorta induced by 5-HT were comparable between the cholesterol-fed group and the age-matched control group. However, acetylcholine-induced vasodilation in arteries preconstricted with 5-HT was moderately but significantly attenuated in the cholesterol-fed rabbits. Platelet aggregation responses to 5-HT (0.1-3 micromol/l) in combination with epinephrine (5 micromol/l), adenosine diphosphate (ADP) (0.3-10 micromol/l), 9,11-dideoxy-9alpha,11alpha-methanoepoxy-prostaglandin F2alpha (U-46619) (1-30 micromol/l) or collagen (3 microg/ml) were significantly enhanced in cholesterol-fed rabbits. In contrast, platelet 5-HT content determined with a high-performance liquid chromatography-electrochemical detector (HPLC-ECD) was significantly decreased in cholesterol-fed rabbits. These results suggest a possible association among the endothelial dysfunction, platelet aggregation and platelet 5-HT content in rabbits with dietary hypercholesterolemia.     

Post-Traumatic Stress Disorder after typhoon disaster and its correlation with platelet 5-HT concentrations

Objective:To investigate residents' psychological stress factors and research the correlation between Post-Traumatic Stress Disorder(PTSD) and platelet 5-HT concentrations so as to provide scientific bases for diagnosis and treatment of PTSD and psychological intervention for people in the disaster area.Methods:A questionnaire survey of 5 500 residents who have accepted psychological help was conducted by the emphatic investigation method.While high performance liquid chromatography were used to detect the platelet serotonin concentration of 100 PTSD patients and 100 healthy people.Results:(1) Of the 5 114 cases,3 167(61.93%) showed positive results in screening for psychological stress symptoms,and 399(7.8%) were tested with apparent PTSD symptoms.Male and female prevalence showed no significant difference(X~2=-0.380,P=0.704).The differences of prevalence between different age groups were statistically significant(X~2=381.89,P=0.000).(2) The differences in the level of platelet 5-HT between PTSD patients and normal control group were statistically significant.Conclusions:The typhoon of Hainan province caused relatively large psychological problems to the disaster victims.Compared with normal control group,the platelet 5-HT levels of PTSD patients in the disaster areas are lower.It may be related to incidents exposure levels,cultural background,religious ideas,social concerns and psychological rescue of the residents who live in the disaster areas of Hainan.     

Modulation of hematopoiesis by ketanserin in erythropoietin-treated uremic patients: evidence from platelet studies

Recombinant human erythropoietin (EPO) not only ameliorates the anemia of renal failure but also modulates platelet function and corrects uremic platelet serotonin (5-hydroxytryptamine, 5-HT) storage pool deficiency. We studied if ketanserin, a blocker of platelet and vascular smooth muscle receptors for 5-HT, could reverse any EPO-induced changes in hemostasis. A complete blood count, immunoreactive serum EPO concentration, skin bleeding time (BT) and whole blood platelet aggregation (electric impedance method) induced by ristocetin and ADP, and intraplatelet and whole blood 5-HT, were determined in seven chronic hemodialysis (HD) patients before and after 1, 2, 4 and 8 weeks of EPO therapy, and repeated after a 4-week co-treatment with oral ketanserin. Stimulation of erythropoiesis was accompanied by a rise in the platelet count ( P < 0.05), shortening of the BT ( P < 0.02), an increase in platelet aggregability, and by replenished intraplatelet 5-HT store. Ketanserin co-treatment produced an unexpected 33% fall in serum EPO level ( P < 0.02), a decrease in the platelet count ( P < 0.05), prolongation of the BT ( P < 0.05) and depressed platelet aggregation in response to both agonists. There was no change in the amount of intraplatelet 5-HT while whole blood 5-HT concentration decreased significantly ( P < 0.02). Strong positive correlations between the decrease in whole blood 5-HT and the prolongation of the BT ( r = 0.786, P < 0.05), and between the former parameter and the fall in the platelet count ( r = 0.820, P < 0.05) were found. In conclusion, we report dual erythro- and thrombocytopoietic effects of EPO combined with correction of a platelet defect in the storage of 5-HT and enhanced platelet aggregability. The ketanserin-induced falls in serum EPO concentration and the platelet count provide new evidence of the dependency of thrombocytopoiesis on EPO in the initial weeks of the therapy. The 'antiplatelet' effects of ketanserin observed in this study seem to be due to reduction in circulating thrombocyte number rather than from any inhibitory effect on their aggregation.     

Effect of long-term ketanserin treatment on 5-HT levels, platelet aggregation and peripheral circulation in patients with Raynaud's phenomenon. A double-blind, placebo-controlled cross-over study

The long-term effects of the serotonergic (5-hydroxy-tryptamine, 5-HT) receptor antagonist, ketanserin, on 5-HT levels in whole blood, platelet aggregation and peripheral circulation were investigated in a double-blind placebo-controlled cross-over study. In 13 patients with Raynaud's phenomenon, 5-HT and catecholamine levels in whole blood were determined and platelet aggregation assayed after addition of ADP, collagen and 5-HT. Peripheral circulation was evaluated with fingertip temperatures and finger plethysmography before and after local cooling, with measurements repeated after indirect sympathetic blockade by body warming and after alcohol. Patients' symptoms were continuously registered in an individual diary. All measurements were performed 8 to 12 hours after the last drug intake. Five of seven scleroderma patients reported beneficial effects of ketanserin treatment and all six patients with primary Raynaud's phenomenon reported less severe and shorter cold-induced attacks. 5-HT levels in whole blood were significantly reduced after 5 weeks of ketanserin treatment (p less than 0.001) with a tendency for persistence of this reduction after halting of the medication (a "carry-over" effect). Platelet aggregation velocity induced by ADP, collagen and 5-HT was unaffected after ketanserin treatment. The diastolic blood pressure in these patients was decreased from 77.5 mmHg to 71.0 mmHg (p less than 0.001) after ketanserin, but the finger systolic blood pressure (FSBP) was unchanged. After sympathetic blockade by body warming, patients with ketanserin treatment had a paradoxical reduction in both FSBP and finger-tip temperatures, which makes a supposed alpha-receptor-blocking effect of ketanserin less likely. The reduced 5-HT levels in whole blood may explain the subjective favourable effect on patients with Raynaud's phenomenon.     

Collagen stimulated release of serotonin by human platelets includes a sulphate conjugated component

Collagen (5-160 μg/ml) induced release of free and sulphate conjugated serotonin (5-HT) from platelets in platelet-rich plasma (PRP) was examined in normal human subjects. Collagen stimulated release of free 5-HT to the plasma (platelet-poor; PPP) increased in a dose dependent manner (P < 0.0001) and was mirrored by a decline in platelet free 5-HT content (P < 0.0001). The half-maximum response occurred at a collagen concentration of 10.5 μg/ml. Non-specific (resting) release of free 5-HT represented 2.5% of the total free 5-HT (sum of PPP and platelet concentrations). On stimulation with 5,10,20,40,80 and 160 μg/ml collagen, PPP free 5-HT concentrations were 24.2, 45.5, 63.2, 74.9, 82 and 89.7% of the total respectively. Collagen also elicited dose dependent release of sulphate conjugated 5-HT to PPP (P < 0.05), which was reflected by a corresponding decline in platelet sulphate conjugated 5-HT content (P < 0.0001). Half maximal release of sulphate conjugated 5-HT occurred with 6 μg/ml collagen. Under resting conditions platelet and PPP sulphate conjugated concentrations were respectively 6 and 35.1% of total (sum of free and sulphate conjugated) 5-HT concentrations, whilst under collagen (160 μg/ml) stimulated conditions these concentrations represented 12.8 and 7.7% of the total. Mobilisation (i.e. hydrolysis) of platelet sulphate conjugated 5-HT did not occur on collagen stimulation, as evidenced by the absence of alterations in total sulphate conjugated 5-HT concentrations (sum of PPP and platelet sulphate conjugated 5-HT concentrations). PPP concentrations of the 5-HT metabolite 5-hydroxyindoleacetic acid (5-HIAA) were unaltered by collagen stimulation indicating that it did not influence 5-HT metabolism. It is concluded that release of platelet sulphate conjugated 5-HT, in addition to free 5-HT, occurs on platelet activation by collagen, although the sulphate conjugated fraction represents only a minor proportion of the total (free and sulphate conjugated) 5-HT released. Further studies will establish the physiological significance of platelet sulphate conjugated 5-HT.     

正常人与冠心病、高血压病人血小板内外5-HT和血小板聚集性增龄性变化的研究

本文对50名正常人血小板及血浆5-羟色胺和血小板聚集性进行了增龄性变化观察并与冠心病和高血压病人的相应指标进行了比较。结果表明,血小板5-羟色胺随龄降低,血浆5-羟色胺和血小板聚集性随龄增高。冠心病及高血压病人血小板5-羟色胺明显降低,而血浆5-羟色胺和血小板聚集性明显增加并与病情轻重有关。     

Doxazosin, an alpha1-adrenoceptor antagonist, inhibits serotonin-induced shape change in human platelets

Patients with peripheral vascular disease or diabetes mellitus tend to have elevated circulating levels of naturally occurring platelet agonists like serotonin (5 hydroxytryptamine; 5-HT). This bioamine can induce platelet shape change (PSC) an early phase of platelet activation, which is essentially aspirin resistant. In addition, 5-HT exerts other harmful effects (eg stimulating vascular smooth muscle proliferation and inducing vasoconstriction in atheromatous coronary vessels). The aim of this study was to determine whether doxazosin inhibits 5-HT-induced PSC. Doxazosin is a long acting alpha(1)-adrenoceptor antagonist, used in the treatment of essential hypertension and/or benign prostatic hyperplasia (BPH). Platelet rich plasma (PRP) was prepared from healthy volunteers (n = 8; five males and three females with a median age of 32 years, range: 26-57). Agonists (5-HT, 0.06-0.5; ADP, 0.1-0.2 micromol/l or U46619, a TXA(2)analogue, 0.025-0.05 micromol/l) were added to PRP and aliquots were removed at specific time points for median platelet volume (MPV) measurement (using a high-resolution channelyser). The MPV was used as an indicator of PSC. PRP was also incubated with doxazosin (final concentration: 0.33 microM, a concentration similar to therapeutic plasma levels) prior to the addition of each of the above-mentioned agonists. Doxazosin significantly inhibited (P = 0.007 and P = 0.008, at 30 sec and 60 sec, respectively) the 5-HT-induced increase in MPV. Doxazosin did not significantly inhibit ADP- or U46619-induced PSC. The inhibitory effect of doxazosin seems to be specific to platelet 5-HT(2) receptors, since there was no effect on ADP- or U46619-induced PSC. This inhibition of platelet activation may be an additional, clinically relevant, advantage. Future in vivo studies should consider assessing the effect of doxazosin on 5-HT-induced platelet activation.     

Metabolism of various biogenic amines in diabetes mellitus

Serotonin (5-HT) and histamine metabolism was studied in 50 patients with diabetes melitus. Simultaneously the blood and urine content of their precursors and metabolites tryptophane, 5-hydroxytryptophane (5-HTP), 5-hydroxyindolylacetic acid (5-HIAA) and histidine was examined. An increase in 5-HT metabolism intensification (the augmented 5-HTP and 5-HT blood levels and enhanced 5-HTP and 5-HIAA excretion with the urine) was determined, whereas the blood and urine contents of histamine and histadine were within normal. Moreover, significantly higher increase in 5-HT blood level and enhanced 5-HIAA excretion with the urine were seen in patients with juvenile diabetes mellitus comparatively to those with insulin-depending type of the disease. Possible significance of changes, being discovered in 5-HT metabolism of patients with diabetes mellitus, in the disease pathogenesis is discussed.