小剂量阿司匹林防治Ⅱ型糖尿病患者视网膜病变的临床研究

为探讨糖尿病视网膜病变的防治方法，对１０６例患Ⅱ型糖尿病（ＮＩＤＤＭ）但尚未出现明显视网膜病变者，在血糖水平基本控制稳定的情况下，随机抽取５３例，日服小剂量阿司匹林（４０￣８０ｍｇ／ｄ），坚持服药２ａ后，观察两组病人眼底病变的发生和改变。结果表明，小剂量阿司匹林组较之对照组的视网膜病变的发生率低且程度轻，二者之间有显著差别（Ｘ＾２＝６．０９，Ｐ〈０．０５）。并对小剂量阿司匹林防治糖尿病微血管病变的     

25-羟基维生素D3水平与2型糖尿病视网膜病变的关系研究

目的探讨血清25羟基维生素D水平与2型糖尿病视网膜病变的关系。方法眼科住院或门诊的2型糖尿病患者，本研究共纳入了99例2型糖尿病伴视网膜病变患者，其中非增值性病变者61例，增值性病变者38例，并纳入了90例2型糖尿病不合并视网膜病变者。本研究控制了各组间年龄、性别、体重指数、病程等重要常规临床参数，先后采用单因素及多因素统计方法，分析了25-羟基维生素D3对糖尿病视网膜病变风险的影响。结果单变量分析结果显示，糖尿病视网膜病变组糖化血红蛋白、TG、25．羟基维生素D3水平差异有统计学意义（P〈0．05）。25羟基维生素D水平在对照组、非增值性视网膜病变组、增值性视网膜病变组逐渐降低，差异有统计学意义（P〈O．05）。多因素Logistie回归分析显示：维生素D不足独立影响非增值性及增值性视网膜病变的风险（P〈0．05），OR值分别为2．15（1．19，7．71），3．36（1．56，7．96）。结论维生素D不足是糖尿病视网膜病变发生的危险因素，补充维生素D可能对预防至治疗糖尿病视网膜病变有益。     

小剂量阿司匹林不同时间给药对2型糖尿病患者CD62P表达的影响

目的：探讨小剂量阿司匹林不同时间给药对2型糖尿病患者血小板膜糖蛋白CD62p,表达水平的影响。方法：56例2型糖尿病不伴微血管病变患者,按就诊时间随机分为阿司匹林晨服组36例（100mg·d^-1,8：00服药）和晚服组20例（100mg·d^-1,20：00服药）,采用流式细胞术测定阿司匹林治疗前后血小板CD62p的表达,采用高效液相色谱法测定水杨酸血药浓度。结果：两组患者服药后CD62p阳性表达率均显著降低,服药前CD62p分别为（7．43±3．25）％,（7．28±2．94）％,服药后分别降为（5．69±2．81）％,（5．83±2．53）％,但两组差值无明显差异（P〉0．05）。水杨酸血药浓度分别为（2．39±0．92）和（0．85～4．11）mg·L^-1,与cD62P差值不相关（r=-0．175;P〉0．05）。结论：口服小剂量阿司匹林能够显著降低2型糖尿病不伴微血管病变患者血小板CD62P的表达水平,时辰给药对CD62P表达水平的影响不显著。     

胰激肽原酶治疗早期糖尿病视网膜病变45例疗效分析

目的观察胰激肽原酶治疗早期糖尿病视网膜病变（DR）的疗效。方法应用胰激肽原酶治疗45例早期DR的2型糖尿病患者,并与拜阿司匹林和复方丹参片治疗的40例对照比较,研究该药对DR患者视网膜病变、视力、眼底变化的疗效。结果治疗组视力、视网膜病变分级等比对照组均有好转,有显著性差异（P〈0．05）。结论胰激肽原酶能有效逆转糖尿病早期视网膜病变,改善眼底微循环,对早期糖尿病视网膜病变有较好疗效。     

糖化血红蛋白检测对糖尿病视网膜病变的临床意义

目的 探讨糖化血红蛋白对糖尿病视网膜病变的临床意义。方法 对2型糖尿病视网膜病变患者110例和2型糖尿病无视网膜病变患者90例用微柱法行糖化血红蛋白检测。结果 糖尿病视网膜病变患者糖化血红蛋白比无视网膜病变患者糖化血红蛋白明显增高，经统计学处理差异有统计学意义（P〈0．01）。结论 控制血糖，降低糖化血红蛋白水平，有助于降低糖尿病视网膜病变发生的危险。糖化血红蛋白是糖尿病患者长期血糖控制情况的一个良好指标。     

DR患者血清中生长因子水平变化的研究

目的探讨2型糖尿病（T2DM）视网膜病变（DR）患者血清中胰岛素样生长因子-Ⅰ（IGF-Ⅰ）、IGF-Ⅱ和IGF结合蛋白-3（IGFBP-3）水平的变化及意义。方法用免疫放射分析法（IRMA）测定50例T2DM患者[包括14例无DR的T2DM患者（NDR）、16例单纯型DR患者（BDR）、20例增生型DR患者（PDR）]及22例正常对照者血清中IGF-Ⅰ、IGF-Ⅱ和IGFBP-3的水平。结果糖尿病组血清中IGF-Ⅰ水平显著高于正常对照组（P〈0．01），IGF-Ⅱ水平显著低于正常对照组（P〈0．01），两者呈显著负相关（r=0．305，P〈0、01）；PDR组IGF-Ⅰ水平显著高于BDR组（P〈0．01），后者又显著高于NDR组（P〈0．05）；PDR组和BDR组IGF-Ⅱ水平显著低于NDR组（P〈0．05）。NDR组、BDR组和PDR组间IGFBP-3水平无显著性差异（P〉0．05）。结论IGF-Ⅰ和IGF-Ⅱ可能参与了DR的病理过程，并与视网膜病变类型相关。     

氧化低密度脂蛋白与糖尿病视网膜病变的相关性研究

目的 测定糖尿病视网膜病变患者血浆氧化低密度脂蛋白（OXLDL）水平，探讨OXLDL水平与糖尿病视网膜病变发生的相关性。方法 对47例2型糖尿病（DM）并糖尿病视网膜病变（DR）患者和44例无DR的DM患者分别检测血脂蛋白，HbA1c水平。结果 DR组OXLDL平均水平高于无DR组（P＜0．05），DR组的糖尿病病程、HbA1c高于对照组。OXLDL、糖尿病病程、HbA1c与DR有独立的相关性。结论 DR患者血清OXLDL水平升高，并可能是DR发生的重要危险因素之一。     

糖尿病视网膜病变甲皱微循环变化

本文对糖尿病并发糖尿病性视网膜病变患者与糖尿病无视网膜病变患者及正常人甲皱微循环检查结果进行了对比，分析如下。临床资料研究对象A组：糖尿病38例，76只眼，男22冽、女16例，年龄19～76岁，平均50．8岁；病人均来自本院住院病人，经临床确诊糖尿病，I型糖尿病4例、Ⅱ型糖尿病34例。B组：正常组28例，均无糖尿病、高血压等全身疾患，眼底检查无动脉硬化的健康体检者，其中男16例、女12例，年龄29～58岁，平均48．6岁。A组38例糖尿病患者按有无糖尿病视网膜病变分为A1及A2组：A1组为有视网膜病变者，A2组为无视网膜病变者。A1组22…     

IL-10在2型糖尿病患者视网膜病变中的变化

目的 研究血清 IL-10在 2型糖尿病视网膜病变发生发展中的作用.方法 选取 2型糖尿病患者,无视网膜病变组 （NDR）30例、单纯型视网膜病变组 （SDR）30例、增殖型视网膜病变组 （PDR）30例.采用 ELISA法测定患者血清 IL-10,并同时采血测定糖化血红蛋白（GHbA1C）、血脂.结果 各组间年龄及性别差异无统计学意义 （ P〉0.05）,各组间 GHbA1C 、TC、TG、LDL、HDL也没有统计学差异.IL-10水平在糖尿病无视网膜病变组、单纯型糖尿病视网膜病变组、增殖型糖尿病视网膜病变组逐渐降低.结论 IL-10在糖尿病视网膜病变发展的过程中起到了保护作用.     

可溶性血管细胞黏附分子-1与2型糖尿病视网膜病变的相关性研究

目的研究2型糖尿病视网膜病变患者血清可溶性血管细胞黏附分子-1（sVCAM-1）水平的变化与糖尿病病程、视网膜病变程度、糖化血红蛋白、胰岛索、血糖及血脂之间的相关性。方法选取2型糖尿病不伴视网膜病变患者[无视网膜病变组（NDR）]20例、2型糖尿病伴背景型视网膜病变患者[背景型视网膜病变组（BDrt）]20例、2型糖尿病伴增殖型视网膜病变患者[增殖型视网膜病变组（PDR）]20例和健康体检（健康组）20例作为健康对照组。应用酶联免疫吸附法（ELISA）测定各组受试者血清sVCAM-1水平,微柱法测定HbAle,放免法测定空腹INS,同时测定FBG、血脂等,并收集糖尿病患者的病程、糖化血红蛋白、胰岛素、直糖、血脂资料,采用单因素方差分析、SNK-q检验和Pearson相关分析比较各组间sVCAM-1水平,sVCAM-1水平与各代谢指标间的相关性。结果PDR组、BDR组和NDR组患者的血清中sVCAM-1的浓度明显增高,与健康对照组比较差异均有统计学意义（均P〈0．001）;PDR组患者血清sVCAM-1的增高较BDR组、NDR组增高明显,差异均有统计学意义（均P〈0．001）;BDR组与NDR组患者血清sVCAM-1浓度相比较差异均无统计学意义（P〉0．05）。糖尿病患者血清sVCAM．1与病程呈正相关（r=0．338,P〈0．05）,与HbAlc、FBG、CHO、TG、LDL、空腹INS均无相关关系。结论糖尿病视网膜病变不同时期血清sVCAM-1水平有不同程度的增高,提示sVCAM-1在视网膜病变的发生发展中起重要作用,并可能成为监测视网膜病变病情变化的有效指标之一。     

Sex difference in the effect of aspirin on rat platelet aggregation and arachidonic acid metabolism

The rat platelet aggregation induced by collagen was stronger in males than in females. The platelet malondialdehyde (MDA) production was more in males than in females, and the platelet cyclooxygenase activity was higher in males than in females. Aspirin at a dose of 10 mg/kg inhibited the collagen-induced aggregation in males, but not in females. Aspirin at a dose of 5 mg/kg blocked the MDA production only in males, but aspirin at a dose of 10 mg/kg inhibited the MDA production in both sexes. The effect of aspirin on the cyclooxygenase activity was only in males, but aspirin at a dose of 10 mg/kg inhibited the MDA production in both sexes. The effect of aspirin on the cyclooxygenase activity was similar to that on the MDA production. In gonadectomized rats, the MDA production and the cyclooxygenase activity were decreased by castration, and they were increased by ovariectomy. Aspirin at a dose of 5 mg/kg failed to inhibit them in castrated rats. Besides, in in vitro experiments, aspirin also inhibited the MDA production and the aggregation. Nevertheless, there was no sex difference in the content of arachidonic acid, a substrate of platelet cyclooxygenase. It is suggested that there is a sex difference in rat platelet cyclooxygenase activity, and it is closely related to the sex difference in the antiplatelet effect of aspirin.     

Aspirin protected against endothelial damage induced by LDL： role of endogenous NO synthase inhibitors in rats

AIM: To study the protective effect of aspirin on damages of the endothelium induced by low-density lipoprotein (LDL), and whether the protective effect of aspirin is related to reduction of nitric oxide synthase inhibitor level.METHODS: Vascular endothelial injury was induced by a single injection of native LDL (4 mg/kg) in rats. Vasodilator responses to acetylcholine (ACh) in the isolated aortic rings were determined, and serum concentrations ofasymmetric dimethylarginine (ADMA), malondialdehyde (MDA), tumour necrosis factor-α (TNF-α), and the activity of dimethylaminohydrolase (DDAH) were measured. RESULTS: A single injection of LDL (4 mg/kg)significantly decreased vasodilator responses to ACh, increased the serum level of ADMA, MDA, and TNF-α, anddecreased DDAH activity. Aspirin (30 or 100 mg/kg) markedly reduced the inhibition of vasodilator responses toACh by LDL, and the protective effect of aspirin at the lower dose was greater compared with high-dose aspiringroup. Aspirin inhibited the increased level of MDA and TNF-α induced by LDL. Aspirin at the dose of 30 mg/kg,but not at higher dose (100 mg/kg), significantly reduced the concentration of ADMA and increased the activity ofDDAH. CONCLUSION: Aspirin at the lower dose (30 mg/kg) protects the endothelium against damages elicitedby LDL in vivo, and the protective effect of aspirin on endothelium is related to reduction of ADMA concentrationby increasing DDAH activity.     

The basis of platelets: platelets and atherothrombosis: an understanding of the lack of efficacy of aspirin in peripheral arterial disease (PAD) and diabetic patients

Platelet activation subsequent to the adhesion of platelets to the vascular wall results in the release of mediators that promote platelet aggregation, which plays a pivotal role in the development of the polyvascular atherosclerotic disease that can be referred to by the acronym 'ATIS' (AtheroThrombosIS). The currently available antiplatelet drugs used to prevent vascular events in patients with cardiovascular disease, including peripheral arterial disease (PAD), include aspirin and thienopyridines such as clopidogrel. These drugs decrease platelet aggregability, each of them by inhibiting a different pathway of platelet activation and recruitment. Aspirin acts by inhibiting thromboxane A2 (TXA2) formation through the inhibition (acetylation) of cyclo-oxygenase. On the other hand, thienopyridines suppress the platelet aggregation adenosine diphosphate (ADP) pathway by inhibiting the platelet P2Y12 subtype of the ADP receptor. The results of the large ATT (Antithrombotic Trialists' Collaboration) meta-analysis of published clinical studies on aspirin, reported in 2002, confirmed the previous meta-analysis and major trials that treatment with aspirin (mixed with other antiplatelet agents in these large meta-analyses) can prevent vascular events in high-risk patients with cardiovascular disease. However, it must be stressed that specifically in PAD patients no significant effect of aspirin was demonstrated in a more recent meta-analysis. This was also the case for primary and secondary prevention in diabetic patients. In keeping with these observations, neither a five-year follow-up study of Japanese diabetic patients in the JPAD (Japanese Primary Prevention of Atherosclerosis with Aspirin for Diabetes) study, a seven-year follow-up study of UK diabetic patients with PAD in the POPADAD (Prevention of Progression of Arterial Disease and Diabetes) study, nor a very recent Scottish study in the same population of diabetics with PAD revealed a significant beneficial effect for aspirin in preventing ischaemic events. This failure may be a consequence of more rapid recovery of platelet aggregability following each dose of aspirin in these PAD or diabetic populations, with the accelerated platelet turnover resulting in a condition of aspirin resistance. Results of the large scale CAPRIE (Clopidogrel versus Aspirin in Patients at Risk of Ischaemic Events) trial that evaluated clopidogrel in patients with cerebral infarction, myocardial infarction or PAD have found clopidogrel to be significantly more effective than aspirin in preventing ischaemic events in patients with PAD. Furthermore, a subgroup analysis of the study has confirmed the efficacy of clopidogrel in diabetic patients with PAD, showing a significant reduction of events in clopidogrel-treated, compared with aspirin-treated, diabetic patients. These results are also likely to be attributable to the greater frequency of aspirin resistance in aspirin-treated patients in these populations (diabetics and/or PAD). Platelets, through activation and aggregation, have an important role in ATIS. However, although antiplatelet therapy with low-dose aspirin has been reported to prevent vascular events in high-risk patients with cardiovascular disease, recent studies in patients with PAD or diabetes mellitus have failed to support the efficacy of aspirin in preventing vascular events in these patient populations. In contrast, clopidogrel appears to be a useful antiplatelet agent in the prevention of vascular events in patients with PAD or diabetes.     

复方姜黄汤预防单纯型糖尿病视网膜病变向增殖型发展的临床疗效观察

目的:观察复方姜黄汤预防单纯型糖尿病视网膜病变向增殖型发展的临床疗效。方法:回顾性分析123例(208眼)单纯型糖尿病视网膜病变患者的临床资料,治疗组64例应用复方姜黄汤,对照组59例应用小剂量肠溶阿司匹林,2组均用降糖药控制血糖。通过眼底镜及荧光素眼底血管造影检查,比较2组临床疗效。结果:治疗组发展成增殖型的比例显著低于对照组。结论:复方姜黄汤能有效抑制视网膜新生血管的形成,防止视网膜病变单纯型向增殖型发展。     

Antiplatelet drugs in cardiovascular prevention: coronary events: acute phase and secondary prevention

(1) Aspirin reduces acute-phase mortality after myocardial infarction, and also reduces the risk of myocardial infarction and death in patients with unstable angina. Aspirin reduces the risk of myocardial infarction in patients with stable angina and after unstable angina, and the risk of relapse after myocardial infarction. It reduces the risk of complications during coronary angioplasty, and the risk of venous coronary bypass graft occlusion after coronary surgery. (2) The best risk-benefit ratio with aspirin is achieved at a daily dose of 75-350 mg; 160 mg/day is the best-validated dose in the acute phase of myocardial infarction. (3) Aspirin must be combined with a thrombolytic agent in patients with myocardial infarction, and with heparin in patients with unstable angina. During coronary stenting the aspirin + clopidogrel combination may have a better risk-benefit ratio than the aspirin + ticlopidine combination. (4) Clopidogrel can be used when aspirin is contraindicated or poorly tolerated. (5) Oral anticoagulants seem a better option than aspirin after complicated myocardial infarction.     

Magnitude and time course of platelet inhibition with Aggrenox and Aspirin in patients after ischemic stroke: the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial

The European Stroke Prevention Study showed greater stroke prevention for Aggrenox than either for aspirin or dipyridamole alone. To test whether Aggrenox has superior antiplatelet properties to aspirin alone we conducted the AGgrenox versus Aspirin Therapy Evaluation (AGATE) trial. Forty patients with prior ischemic stroke not taking aspirin for at least 30 days were randomized to Aggrenox (2 pills/daily) or aspirin (81 mg plus matching placebo/daily) for 30 days. Platelet function was assessed at baseline, 24 h, and days 3, 7, 15, and 30 by aggregometry, flow cytometry and cartridge-based analyzers. Both Aggrenox and aspirin provided fast and sustained platelet inhibition. Aggrenox(R), however, especially after 15 days, showed significant prolongation of the closure time (P=0.04), diminished expression of platelet/endothelial cell adhesion molecule-1 (PECAM-1) (P=0.01), glycoprotein IIb (GPIIb) antigen (P=0.02), and GPIIb/IIIa activity (P=0.01) by PAC-1 C antibody, CD63 (P=0.03), as well as inhibition of Protease Activated Receptors (PAR-1) associated with intact (SPAN12, P=0.01) and cleaved (WEDE15, P=0.01) thrombin receptors as compared with aspirin. Surprisingly, GPIb expression increased, especially after aspirin. In the randomized trial of small sample size, aspirin and Aggrenox produced fast and sustained platelet inhibition. In 25 of 90 direct comparisons, Aggrenox was superior to aspirin, whereas in 4 of 90, aspirin was superior to Aggrenox. In 61 of 90 direct comparisons, aspirin and Aggrenox were equivalent. Aggrenox was associated with a profound reduction of PAR-1 receptors, an observation that may be related to the greater clinical benefit of Aggrenox compared with Aspirin in preventing recurrent stroke.     

我院2型糖尿病患者阿司匹林的应用情况调查

目的:调查2型糖尿病患者应用阿司匹林的情况。方法:对我院2004年4月～2007年4月内分泌科510例2型糖尿病住院患者阿司匹林的应用情况进行回顾性分析。结果:我院内分泌科2型糖尿病住院患者阿司匹林的应用率为68.2%,日剂量达50～100mg,合并冠心病、高血压者阿司匹林应用率较高(P<0.05)。结论:我院2型糖尿病患者阿司匹林应用率较高,在应用年龄及应用剂量上应加强规范化管理。     

阿司匹林抑制ox-LDL诱导内皮细胞炎症分子表达的研究

目的评价阿司匹林对ox-LDL刺激内皮细胞炎症蛋白表达的影响。方法使用培养人脐带内皮细胞,用氧化型低密度脂蛋白刺激内皮细胞16h,终止反应后用SDS-PAGE分离蛋白,使用Western Blot分析蛋白表达的变化。ROS测定使用DCFH-DA荧光标记,用流式细胞仪测定荧光强度。结果①阿司匹林抑制ox-LDL诱导内皮细胞COX-2表达。使用ox-LDL刺激内皮细胞16h,COX-2表达增加,分别用2.5mmol·L-1和5mmol·L-1阿司匹林处理内皮细胞30min后,COX-2表达明显降低。②阿司匹林降低ox-LDL诱导的内皮细胞ICAM-1表达。ox-LDL刺激内皮细胞16h后,Western Blot结果显示ICAM-1内皮细胞表达明显增加。用免疫荧光染色的方法观察细胞获得了同样的结果,ox-LDL刺激后ICAM-1在内皮细胞膜上表达明显增加,阿司匹林处理后减少了ICAM-1在膜上的表达。③阿司匹林轻度抑制ox-LDL诱导内皮细胞ROS产生。0.3g·L-1ox-LDL刺激内皮细胞16h后细胞内ROS明显增高,但阿司匹林仅部分阻止ROS的产生。结论非甾体类抗炎药物阿司匹林对ox-LDL诱导COX-2、ICAM-1有明显的抑制作用,但不能完全阻止ox-LDL诱导的ROS产生。这些结果表明阿司匹林能够减轻氧化脂质诱导的内皮细胞炎症损伤反应。     

不同剂量阿司匹林治疗老年急性脑梗死的疗效及安全性评价

目的探讨不同剂量阿司匹林在老年急性脑梗死治疗中的疗效及安全性。方法选择2011年3月至2012年3月老年急性脑梗死住院患者126例,随机分为A组41例,B组48例,C组37例。3组患者入院后给予阿司匹林肠溶片口服,剂量分别为100,200,300 mg/d,其余治疗相同,即均给予H2受体拮抗剂预防应激性溃疡、中药活血化瘀、改善脑代谢、控制血糖血压、调脂等综合治疗,疗程均为14 d。分别于治疗前后进行神经功能缺损评分,观察不良反应,比较疗效及安全性。结果治疗后经临床疗效评定,A,B,C组总显效率分别为51.22%,70.83%,72.97%,总有效率分别为70.73%,89.85%,86.49%。A组总显效率及总有效率均明显低于B组与C组(P<0.05),B组与C组之间的总显效率及总有效率比较无明显统计学意义(P>0.05),提示阿司匹林治疗老年急性脑梗死中的疗效与剂量有关,但并不完全呈正相关。不同剂量阿司匹林治疗中均可出现消化道损伤,发生率与阿司匹林剂量相关。结论200 mg/d剂量阿司匹林在老年急性脑梗死治疗中疗效与安全性的性价比高,值得临床推荐。