茶多酚对高蛋氨酸饮食诱导大鼠纤维蛋白溶解功能损伤的影响

目的 研究茶多酚( tea polyphenols,TP)对蛋氨酸诱导大鼠纤维蛋白溶解功能损伤的保护作用。方法 取成年雄性Wistar大鼠50只,按体重分层随机分为对照组、模型组,以及TP低、中和高剂量组。对照组喂饲正常基础饲料,模型组及TP组均喂饲3％高蛋氨酸饲料,同时TP低、中、高剂量组每天经灌胃分别给予50、100和200 mg/kg的TP,灌胃体积均为0.5ml/100 9,对照组和模型组给予等体积蒸馏水。8周后断头处死大鼠,采用免疫组织化学链霉亲和素-生物素-过氧化物酶复合物（strept-avidin-biotin complex,SABC）法测定大鼠主动脉弓组织型纤溶酶原激活物（tissue-type plasminogen activator,t-PA）和纤溶酶原激活物抑制剂-1（type-1 plasminogen activator inhibitor,PAI-1）蛋白表达结果;ELISA法测定血浆中t-PA和PAI-1含量;RT-PCR法测定胸主动脉t-PA和PAI-1 mRNA水平。结果 实验结束后,对照组、模型组及TP低、中、高剂量组主动脉弓中t-PA蛋白表达量分别为133.03±10.14、95.46±11.08、111.97±11.91、130.23±10.80、139.39±9.41 (F= 14.15,P＜0.01),PAI-1蛋白表达量分别为90.91±8.67、166.76±12.18、139.63±12.71、134.66±13.19、109.49±10.82(F=31.44,P＜0.01);血浆中tPA含量分别为(10.69±1.26)、(6.13±0.92)、(8.56±1.19)、(9.69±0.92)、(11.97±1.08) ng/ml(F=41.98,P＜0.01),PAI-1含量分别为(6.31±0.81)、(16.98±1.27)、(11.39±0.82)、(8.46±0.67)、(8.08±0.91) ng/ml(F= 207.74,P＜0.01);t-PA mRNA水平分别为1.12±0.02、0.75±0.14、1.01±0.09、0.95±0.08、1.05±0.13(F=5.77,P＜0.05);PAI-1 mRNA水平分别为1.25±0.11、1.74±0.06、1.23±0.05、1.09±0.14、1.23±0.04(F=23.56,P＜0.01)。结论 TP能够调节t-PA和PAI-1的转录及蛋白水平,维持t-PA和PAI-1的平衡状态,修复高蛋氨酸饮食诱导的大鼠纤维蛋白溶解功能损伤。     

茶多酚体外对人血管内皮细胞纤溶功能的保护

目的研究茶多酚(TP)对体外培养的人脐静脉内皮细胞(HUVEC)纤溶功能的保护作用。方法甲基噻唑基四唑(MTT)法筛选不影响细胞增殖的TP和Hcy浓度。实验分为同型半胱氨酸(Hcy)0.5mmol/L、TP10μg/ml、Hcy0.5mmol/L+TP10μg/ml与对照共4组,用酶结合免疫吸附测定(ELISA)法检测培养细胞上清液中纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)含量,反转录聚合酶链反应(RT-PCR)观察t-PA和PAI-1 mRNA水平。结果与对照组相比,Hcy0.5mmol/L可使PAI-1含量增高6.57%,mRNA水平增高45.7%,差异均有统计学意义(P<0.01);TP与Hcy共同作用后则可使PAI-1含量及mRNA水平较Hcy组分别降低8.8%和25.9%,均有统计学差异(P<0.01)。TP可逆转Hcy引起的t-PA mRNA水平下降,使其增高38.1%(P<0.01),但各组t-PA含量均未见改变;TP可保持PAI-1/t-PA比值接近正常水平。结论TP可通过调节mRNA水平来降低PAI-1含量,使PAI-1/t-PA接近正常水平,从而维持内皮细胞的正常纤溶功能。     

糖化血红蛋白对糖尿病肾病早期患者纤溶酶原激活物抑制物-1的影响

目的 探讨糖化血红蛋白(GHbA1c)对糖尿病肾病(DN)早期患者组织型纤溶酶原激活物(t-PA)以及纤溶酶原激活物抑制物-1(PAI-1)活性的影响.方法 2004年4月至2005年5月收治DN早期患者90例.根据GHbA1c水平分为3组,每组各30例.A组GHbAlc＜7%,B组GHbA1c7%-9%,C组GHbA1c＞9%,另选择健康体检者30例作为对照组.所有入选者在清晨空腹抽血测定GHbA-C、t-PA、PAI-1.结果 与对照组比较,DN各组GHbAlC、t-PA、PAI-1差异均有统计学意义(P＜0.05或＜0.01),其中t-PA活性下降,而PAI-1活性上升.C组与A组比较t-PA活性下降[分别为(0.14±0.06)、(0.28±0.11)U/ml],PAI-1活性上升[分别为(3.25±1.01)、(1.90±1.09)U/m1],差异均有统计学意义(P＜0.05);而B组与A组比较t-PA活性有下降趋势,PAI-1活性有上升趋势,但差异均无统计学意义(P＞0.05).结论 DN早期患者体内存在着纤溶系统的失衡,持续高血糖状态进一步破坏纤溶系统,严格控制GHbA1c达标是延缓糖尿病及其并发症发生和发展的重要因素之一.     

茶多酚对同型半胱氨酸诱导损伤的人血管内皮细胞纤溶功能的影响

目的研究茶多酚(TP)对同型半胱氨酸(Hcy)损伤的人脐静脉内皮细胞(HUVEC)形态及组织型纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PAI-1)含量的影响。方法将HUVEC分为同时给予TP和Hcy组与先给予Hcy再给予TP组,各组又按TP浓度不同分成若干小组,根据细胞形态变化和ELISA法测定细胞上清液中t-PA和PAI-1的含量变化。结果无论同时给予TP和Hcy组还是先给予Hcy再给予TP组,中浓度(4、8μg/ml)和高浓度(16μg/ml)TP组细胞形态较单纯Hcy组细胞形态规则,立体感增强,胞浆内颗粒减少。ELISA结果显示,单纯Hcy组与正常对照组相比,PAI-1含量增加(P<0.05),含中、高浓度TP组,PAI-1含量较单纯Hcy组降低,且与TP浓度呈剂量依赖性降低(P<0.05),低浓度TP组PAI-1含量与单纯Hcy组差异无显著性;各组t-PA差异均无显著性。结论一定浓度的TP可以恢复Hcy引起的HUVEC细胞形态改变,且可以逆转Hcy引起的PAI-1含量增高的现象。     

探讨高血压患者治疗前后纤溶状态及胰岛素水平变化的临床意义

目的了解高血压患者经怡那林治疗前后纤溶及胰岛素抵抗水平,对二者与高血压疾病的关系进行初步探讨。方法采用ELISA、发色底物法以及RIA方法分别检测高血压患者治疗前后血浆纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制剂1(PAI-1)含量、活性及胰岛素水平的变化。结果与治疗前比较高血压治疗后t-PA和PAI-1水平均有下降趋势,t-PA活性上升,PAI-1活性下降,胰岛素水平降低,差异均有统计学意义(均P<0.05)。结论部分高血压患者常有胰岛素水平的增高并伴随PAI-1活性增高。提示在这些高血压患者治疗中应重视对高胰岛素血症的控制。     

谷胱甘肽治疗脓毒症急性肾损伤患者血清tPA和PAI-1的影响

目的探讨谷胱甘肽对脓毒症致急性肾损伤患者血清组织纤溶酶原激活物(Tissue Plasminogen Activator,tPA)、纤溶酶原激活物抑制物-1(Plasminogen Activator Inhibitor-1,PAI-1)及血管性血友病因子(von willebrand factor,vWF)的影响。方法选取2016年2月-2017年12月于胜利油田中心医院就诊的脓毒症致急性肾损伤患者124例为研究对象,采用数字随机法分为对照组和研究组,各62例;对照组常规静脉滴注前列地尔,研究组在对照组的基础上联合静脉滴注谷胱甘肽,比较两组患者的肾功能尿素氮(blood urea nitrogen,BUN),血清肌酐(Serum creatinine,Scr),中性粒细胞明胶酶相关脂质运载蛋白(Neutrophilgelatinase-associated lipocalin, NGAL),血清胱抑C(Cystatin C,Cys-C)和白细胞介素-8(interleukin,IL-8),血清tPA、PAI-1、vWF和急性生理与慢性健康评分(Acute Physiology and Chronic Health Evaluation, APACHEⅡ)变化。结果治疗前两组患者的肾功能指标BUN、Scr、NGAL、Cys-C和IL-8差异无统计学意义,治疗后两组患者以上指标均下降,且研究组以上指标分别为(8.05±0.98)mmol/L,(162.54±18.65)μmol/L,(45.45±4.89)μg/L,(0.96±0.12)mg/L和(82.73±8.98)μg/L均低于对照组(P<0.05)。两组治疗前的tPA、PAI-1和vWF差异无统计学意义,治疗后研究组以上指标分别为(4.90±0.54)ng/ml、(18.43±2.34)ng/ml和(145.32±18.54)%低于对照组,且治疗后研究组的APACHEⅡ评分为(10.02±3.11)低于对照组(P<0.05)。结论在脓毒症致急性肾损伤患者采用谷胱甘肽治疗可改善肾功能,降低体内tPA、PAI-1水平。     

糖化血红蛋白对糖尿病肾病早期患者纤溶酶原激活物抑制物1的影响

目的探讨糖化血红蛋白（GHbA1c）对糖尿病肾病（ON）早期患者组织型纤溶酶原激活物（t-PA）以及纤溶酶原激活物抑制物-1（PAI-1）活性的影响。方法2004年4月至2005年5月收治DN早期患者90例。根据GHbA1c水平分为3组,每组各30例。A组GHbA1c〈7％,B组GHbA1c7％-9％,c组GHbA1c〉9％,另选择健康体检者30例作为对照组。所有人选者在清晨空腹抽血测定GHbA1c、t-PA、PAI-1。结果与对照组比较,DN各组GHbA1c、t-PA、PAI-1差异均有统计学意义（P〈0．05或〈0．01）,其中t-PA活性下降,而PAI-1活性上升。C组与A组比较t-PA活性下降[分别为（0．14±0．06）、（0．28±0．11）U/ml],PAI-1活性上升[分别为（3．25±1．01）、（1．90±1．09）I／ml],差异均有统计学意义（P〈0．05）;而B组与A组比较t-PA活性有下降趋势,PAI-1活性有上升趋势,但差异均无统计学意义（P〉0．05）。结论DN早期患者体内存在着纤溶系统的失衡,持续高血糖状态进一步破坏纤溶系统,严格控制GHbA1c达标是延缓糖尿病及其并发症发生和发展的重要因素之一。     

联合检测PAI-1、t-PA水平在2型糖尿病大血管病变的临床意义

目的 探讨联合检测合并大血管病变的2型糖尿病患者血浆纤溶酶原激活物抑制物-l(PAI-1)、组织纤溶酶原激活剂(t-PA)水平的临床价值.方法 检测36例合并大血管病变的2型糖尿病患者(A组)、32例无并发症的2型糖尿病患者(B组)和30例健康体检者(对照组)的血浆PAI-1、t-PA水平,同时检测三组研究对象的血糖、血脂等常规生化指标,并对结果进行统计学处理分析.结果 A组患者血浆PAI-1、t-PA水平与B组患者及正常对照组比较差异均有统计学意义(P＜0.05);A组患者FPG、HbA1c、TG、TC、LDL-c等指标与B组患者比较差异无统计学意义(P＞0.05),与正常对照组比较差异有统计学意义(P＜0.01);A组患者HDL-c与B组患者及正常对照组比较差异无统计学意义(P＞0.05).结论 PAI-1、t-PA水平与2型糖尿病患者大血管病变密切相关,联合检测2型糖尿病患者的PAI-1、t-PA水平对大血管并发症的诊断、预防和治疗具有很好的价值.     

卡维地洛对高血压病患者纤溶活性及胰岛素抵抗的影响

目的探讨卡维地洛对高血压病患者纤溶活性及胰岛素抵抗的影响.方法经2w导入期后,给予41例高血压病患者口服卡维地洛,治疗前及治疗8w后,采静脉血测定血浆纤溶酶原激活物(t-PA)、纤溶酶原激活物抑制剂1(PAI-1)活性;空腹胰岛素、空腹血糖,计算胰岛素敏感性指数.结果卡维地洛治疗30d后,患者收缩压和舒张压均有效下降,t-PA活性上升,PAI-1活性下降,空腹胰岛素降低,胰岛素敏感指数显著升高.结论卡维地洛可有效降低高血压病患者的血压,改善纤溶活性和胰岛素抵抗.     

早期急性肺栓塞患者血浆D-二聚体、乳酸脱氢酶同工酶3、组织型纤溶酶原激活物变化及其临床意义

目的 探讨血浆D-二聚体(DD)、乳酸脱氢酶同工酶3(LDH3)、组织型纤溶酶原激活物(t-PA)在早期急性肺栓塞患者中的变化及其临床意义.方法 选取46例早期急性肺栓塞患者(肺栓塞组)及同期门诊正常体检无异常者50例(对照组),急性肺栓塞患者按照病情分为低危18例,中危15例,高危13例,对其进行DD、LDH3及t-PA检测.结果 肺栓塞组DD、LDH3及t-PA分别为(2.95±0.73) mg/L、(421.42±63.29) U/L、(0.85±0.02) U/L,对照组分别为(0.03±0.01) mg/L、(198.17±23.37) U/L、(0.59±0.02) U/L,肺栓塞组DD、LDH3及t-PA明显高于对照组(P＜0.05).低危患者DD、LDH3、t-PA分别为(1.49±0.04) mg/L、(315.47±38.24) U/L、(0.63±0.01) U/L,中危患者分别为(2.22±0.27) mg/L、(382.41±54.36) U/L、(0.79±0.02) U/L,高危患者分别为(3.38±0.98)mg/L、(583.93±117.21) U/L、(0.92±0.03) U/L,中、高危患者与低危患者比较差异有统计学意义(P＜0.05);高危患者LDH3、t-PA与中危患者比较差异有统计学意义(P＜0.05).肺栓塞组治疗后DD、LDH3、t-PA分别为(1.03±0.11) mg/L、(223.24±25.04) U/L、(0.62±0.02) U/L,较治疗前明显下降(P＜0.05).结论 在早期急性肺栓塞患者中DD、LDH3及t-PA均明显升高,随着病情缓解会逐渐下降,联合检测有助于急性肺栓塞的早期诊断.     

Comparison of t-PA and u-PA levels in maximal treadmill and deep-water running

BACKGROUND: The differences of urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA) between maximal treadmill and deep-water running have not been reported. The purpose of this investigation was to compare u-PA and t-PA levels during maximal treadmill and deep-water running. METHODS: Six male subjects carried out two maximal exercises, one on a treadmill and the other running in deep water using a vest. The u-PA, t-PA, total plasminogen activator inhibitor (PAI-1), epinephrine, and norepinephrine in plasma and lactate and ammonia in blood concentrations were measured after maximal exercise. RESULTS: The blood lactate and ammonia concentrations were significantly higher in treadmill running than in deep-water running during recovery following exercise (P < 0.05). At 1 min after exercise, the plasma epinephrine, norepinephrine levels, and the u-PA and t-PA levels were higher in treadmill running compared with that in deep-water running (P < 0.05). No significant difference between the two runs was found in PAI-1 level. CONCLUSION: The maximal treadmill running induced a greater increase in u-PA and t-PA levels than maximal deep-water running.     

Plasma fibrinogen, tissue plasminogen activator, plasminogen activator inhibitor 1, and their related factors in three Japanese population samples

To examine population mean variations in plasma fibrinogen and fibrinolytic variables, and their rela tions with cardiovascular risk characteristics among Japanese middle-aged men, a cross-sectional study was conducted for a total of 245 men aged 50–59 years in three population-based samples: residents in rural communities of northeast and central Japan and urban white-collar workers. Age-adjusted mean value of plasma fibrinogen, tissue plasminogen activator antigen (t-PA antigen), plasminogen activator inhibitor 1 antigen (PAI-1 antigen) did not differ significantly among the populations. Mean value of tissue plasminogen activator activity (t-PA activity) was lower in central rural residents than in northeast rural men. According to multiple linear regression analyses, there were positive associations of t-PA and PAI-1 antigens with serum triglyceride levels, serum insulin and waist-hip ratio within each population and the total samples. A positive association between these fibrinolytic variables and usual ethanol intake was also observed. Smoking was significantly associated with plasma fibrinogen and PAI-1 antigen but not with t-PA antigen or activity. Activity of t-PA was inversely associated with body mass index, and a mean difference in t-PA activity was in part explained by a mean difference in body mass index. In conclusion, population mean values of plasma fibrinogen and fibrinolytic variables did not differ among three Japanese populations except for mean t-PA activity. Reduced fibrinolysis expressed as increased PAI-1 antigen was associated with smoking and the status of insulin resistance, such as high levels of serum insulin, serum triglycerides and waist-hip ratio.     

Metabolic and fibrinolytic response to changed insulin sensitivity in users of oral contraceptives

The fundamental role of insulin resistance for metabolic changes linked to cardiovascular disease and type 2 diabetes is increasingly recognized. Oral contraceptives (OC) may affect insulin sensitivity, and a detailed characterization hereof, as well as the secondary effects on related metabolic systems, are relevant in the evaluation of the risk of developing vascular disorders or diabetes in OC users. We studied insulin sensitivity index (S_I), glucose effectiveness (S_g), and insulin response in young, healthy women by frequently sampled intravenous glucose tolerance tests before and after randomization to 6 months of treatment with ethinyl estradiol in triphasic combination with norgestimate (n = 17) or gestodene (n = 20). Measurements of fasting triglycerides and antigen concentrations of tissue-type plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were also included.

Both compounds increased fasting plasma insulin and reduced S_i but did not affect S_g. The relationships between S_i and insulin response were unchanged. No consistent correlation between insulin sensitivity and triglycerides, t-PA, or PAI-1 were demonstrated before or during treatment. We conclude that the treatments were followed by a compensated decrease in insulin sensitivity that was unrelated to changes in triglycerides, t-PA, or PAI-1 antigen.     

尿激酶型纤溶酶原激活物及其特异受体和抑制物与乳腺癌浸润转移及预后关系的探讨

目的通过免疫组织化学方法研究乳腺癌和乳腺良性病变中尿激酶型纤溶酶原激活物(uPA)及其特异受体(uPA-R)和抑制物(PAI-1)的表达,并探讨其生物学意义。方法将存档的乳腺癌(观察组)和乳腺良性病变(对照组)石蜡标本重新制备3μm切片进行免疫组织化学SP法染色观察。用uPA、uPA-R、PAI-1单克隆抗体分别检测uPA、uPA-R、PAI-1在两组标本中的表达。结果uPA、uPA-R、PAI-1在观察组中表达的阳性率明显高于对照组,淋巴结转移病例中uPA、uPA-R表达的阳性率明显高于淋巴结未转移病例,uPA、uPA-R、PAI-1的表达与TNM分期及肿瘤大小相关,与雌激素受体(ER)、孕激素受体(PR)无关,在病理分级较差的病例中,uPA、uPA-R、PAI-1也有不同程度升高。uPA、uPA-R、PAI-1同时阳性的乳腺癌病例有较高的浸润转移倾向。结论uPA、uPA-R、PAI-1的表达与乳腺癌浸润转移相关,是预测乳腺癌预后的一个强有力的生物学指标。     

髋关节置换手术患者局部纤溶活性指标的变化

目的探讨髋关节置换手术创伤后机体的局部纤溶活性指标的变化及与发生深静脉血栓的关系。方法选择髋关节置换手术患者10例,分别于术前、安装髋臼假体时、安装股骨假体时、皮肤缝合时、术后1 h和术后20 h采用股静脉插管采集患者双侧肢体的血液标本,检测组织型纤溶酶原激活剂(t-PA),组织型纤溶酶原激活剂抗原和纤溶酶原激活物抑制剂-1(PAI-1)三项指标。结果术中术侧肢体的组织型纤溶酶原激活剂抗原和纤溶酶原激活物抑制剂-1比术前显著增加。在术中及术后1 h内,术侧和非术侧肢体中的组织型纤溶酶原激活剂抗原和纤溶酶原激活物抑制剂-1有显著差异。在安装股骨假体时,术侧和非术侧肢体中的组织型纤溶酶原激活剂(t-PA)有显著差异。结论手术创伤对局部纤溶系统的影响不同于非术侧肢体。全髋关节置换术后血栓形成机制相关与局部纤溶系统的临床相关性仍需进一步阐述。     

Effect of plasmin, plasminogen activators and a plasmin inhibitor on bovine in vitro embryo production

In the present study, four experiments were conducted to investigate the possible effects of plasminogen activators (urokinase-type plasminogen activator (u-PA) and tissue-type plasminogen activator (t-PA)), plasmin, and a plasmin inhibitor (epsilon-aminocaproic acid (epsilon-ACA)) on different stages of bovine in vitro embryo production (IVP). The concentrations of these modifiers in IVP media were conditioned according to the plasminogen activator activity of bovine preovulatory follicular fluid. Media were modified in a single phase of IVP with an 18 h or 24 h incubation for in vitro maturation (IVM) and a 24 h or 48 h incubation for the IVF or in vitro culture (IVC), respectively. After IVM the oocytes were either fixed and stained or underwent IVF and IVC. The main findings were: (1) plasmin added to the 18 h IVM medium increased maturation rate without affecting fertilisation or embryo development rates; (2) t-PA added to the IVF medium significantly increased cleavage; (3) u-PA added to the IVC medium significantly increased embryo development rates; (4) the efficiency of all phases of IVP was reduced after the addition of epsilon-ACA; and (5) plasminogen addition had no effect in any IVP phase tested. We conclude that the members of the plasminogen activator-plasmin system contribute in different ways to bovine IVM, IVF and IVC.