髂股静脉血栓形成后综合征的早期手术治疗及相关实验研究

目的 动物实验分析髂股静脉血栓形成(IFVT)后纤溶激活和管壁重塑发生时间,确定髂股静脉血栓形成后综合征(irx,rs)的发生时间;对比分析早期和中晚期手术治疗IFPTS的疗效,探寻最佳手术时机.方法 建立大鼠IFVT模型,采用免疫组化方法检测管壁组织纤溶酶原激活物(tPA)和尿激酶型纤溶酶原激活物(uPA)表达.采用弹力、胶原纤维染色方法检测内弹力膜阳性率,血管周径和管壁僵硬指数.将1990年1月至2005年12月收治的51例接受大隐静脉交叉转流术的IFPTS患者分为早期治疗组(IFVT后1～2个月,n=21),中晚期治疗组(IFVT后>2个月,n=30).用下肢慢性静脉功能不全症状评分标准(VCSS)评估治疗效果.结果 大鼠静脉管壁tPA和uPA在IFVT后2周和4周表达明显增加(P<0.05).管壁内弹力膜阳性率在4、8和12周明显下降(P<0.01),血管周径在12周明显增大(P<0.05),管壁僵硬指数在4、8和12周明显上升(P<0.01).早期治疗组症状改善明显,术后和术前VCSS差异有统计学意义(3.4±0.9比5.2±1.1,P<0.05),中晚期治疗组症状变化无统计学意义(6.8±1.7比7.6±3.0,P>0.05).结论 IFFTS发生时间在血栓形成后1个月左右.IFVT后1～2个月是大隐静脉交叉转流术治疗IFFIS的最佳手术时机.     

髂股静脉血栓形成后综合征的早期手术治疗及相关实验研究

目的 动物实验分析髂股静脉血栓形成(IFVT)后纤溶激活和管壁重塑发生时间,确定髂股静脉血栓形成后综合征(irx,rs)的发生时间;对比分析早期和中晚期手术治疗IFPTS的疗效,探寻最佳手术时机.方法 建立大鼠IFVT模型,采用免疫组化方法检测管壁组织纤溶酶原激活物(tPA)和尿激酶型纤溶酶原激活物(uPA)表达.采用弹力、胶原纤维染色方法检测内弹力膜阳性率,血管周径和管壁僵硬指数.将1990年1月至2005年12月收治的51例接受大隐静脉交叉转流术的IFPTS患者分为早期治疗组(IFVT后1～2个月,n=21),中晚期治疗组(IFVT后>2个月,n=30).用下肢慢性静脉功能不全症状评分标准(VCSS)评估治疗效果.结果 大鼠静脉管壁tPA和uPA在IFVT后2周和4周表达明显增加(P<0.05).管壁内弹力膜阳性率在4、8和12周明显下降(P<0.01),血管周径在12周明显增大(P<0.05),管壁僵硬指数在4、8和12周明显上升(P<0.01).早期治疗组症状改善明显,术后和术前VCSS差异有统计学意义(3.4±0.9比5.2±1.1,P<0.05),中晚期治疗组症状变化无统计学意义(6.8±1.7比7.6±3.0,P>0.05).结论 IFFTS发生时间在血栓形成后1个月左右.IFVT后1～2个月是大隐静脉交叉转流术治疗IFFIS的最佳手术时机.     

组织型纤溶酶原激活物在周围神经损伤修复中的作用及其研究进展

纤溶酶原激活物(plasminogen activators,PAs)是一类丝氨酸蛋白酶,包括组织型纤溶酶原激活物(tissue PA,tPA)和尿激酶型纤溶酶原激活物(urokinase PA,uPA)两种类型,主要作用是催化纤溶酶原转变为有活性的纤溶酶.     

深静脉血栓形成后纤溶激活与管壁重塑的研究

目的 通过检测深静脉血栓形成后纤溶激活与管壁重塑变化,探讨深静脉血栓形成后综合征(PTS)的发病机制.方法 建立大鼠股静脉血栓模型,检测术后1、2、4、8和12周管壁组织型纤溶酶原激活剂(tPA)和尿型纤溶酶原激活剂(uPA)表达规律;计算内弹力膜阳性率,中膜胶原纤维阳性率,中膜细胞核密度,血管周径和管壁僵硬指数.结果 术后2、4周tPA内膜阳性率高于中膜[(55.58±6.42)%比(37.66±5.73)%;(62.71±4.93)%比(41.26±8.25)%,P＜0.05],而uPA阳性率则以中膜为主[(43.08±5.06)%比(59.26±4.08)%;(46.85±5.03)%比(59.17±4.00)%,P＜0.05];术后4、8、12周内弹力膜阳性率和中膜细胞核密度与对照组比较分别有显著性降低和升高(P＜0.01),中膜胶原纤维阳性率无明显变化;术后12周血管周径增大(P＜0.05),管壁僵硬指数增高(P＜0.01).结论 血栓形成后早期静脉壁内存在纤溶激活和管壁重塑.tPA通过降解弹性纤维、uPA通过促进平滑肌细胞增殖共同参与了管壁重塑的调控,两者可能在PTS的形成和发展中起着重要的作用.     

睾酮对人血管内皮细胞tPA、PAI-1基因表达的影响

目的:观察睾酮对人血管内皮细胞(HUVEC)纤溶酶原激活物(tPA)及其抑制物1(PAI-1)表达的影响。方法:将体外培养的HUVEC分别与4个浓度睾酮组(3、30、3×103、3×104nmol/L)及单纯培养液对照组作用48h,RT-PCR法观察各组tPA、PAI-1 mRNA表达水平。结果:生理浓度睾酮组(3和30 nmol/L)tPA mRNA水平明显高于对照组,PAI-1 mRNA水平均明显低于对照组(P均<0.05)。3×104nmol/L睾酮组tPA、PAI-1 mRNA水平均明显降低(P<0.05)。结论:生理浓度睾酮通过促进tPA表达,抑制PAI-1合成,增强纤溶系统活性,有利于防止男性冠心病等血栓性疾病。     

前交叉韧带损伤后尿激酶型纤溶酶原激活物形成变化的实验研究

[目的]探讨前交叉韧带损伤后尿激酶型纤溶酶原激活物形成变化。[方法]20只新西兰兔一期建立单侧前交叉韧带损伤模型。损伤术前、术后2、4和8周时采用ELISA检测血浆中尿激酶型纤溶酶原激活物含量变化。损伤术后8周时采用HE染色和免疫组织化学检测关节内组织病理变化和尿激酶型纤溶酶原激活物表达情况。[结果]前交叉韧带损伤后血浆尿激酶型纤溶酶原激活物含量变化明显,术后2周时尿激酶型纤溶酶原激活物含量显著增高(P<0.05)。术后8周时组织学检测显示滑膜、软骨和前交叉韧带呈病理改变,组织内尿激酶型纤溶酶原激活物广泛表达、阳性细胞数量增多(P<0.01)。[结论]前交叉韧带损伤后关节腔内多种组织尿激酶型纤溶酶原激活物表达异常,血浆尿激酶型纤溶酶原激活物含量变化明显。     

纤维蛋白对肾小球内皮细胞表达纤溶酶原激活物及纤溶酶原激活物抑制物的作用

目的：观察体外培养人肾小球内皮细胞（GEC）表面原位形成的纤维蛋白对GEC表达纤溶酶原激活物及纤溶酶原激活物抑制物（PA／PAI）的影响。方法：应用逆转录聚合酶链反应（RT－PCR）,酶谱分析法与反向酶谱法分别在基因转录水平与蛋白质活性水平上检测纤维蛋白对GEC表达tPA,uPA gn PAI-1r 作用,纤维蛋白平板法检测纤维蛋白对GEC PA／PAI系统的综合效应,结果：纤维蛋白能够明显促进tPA,uPA与PAI－1的mRNA表达上调,无血清RPMI 1640培养下的GEC几乎检测不到PAI知性,但可检测到PAI－1的活性。纤维蛋白能够浓度依赖性刺激GEC tPA与uPA活性增加以及PAI01的活性增加,呈浓度依赖性与时间依赖性,相同剂量的纤维蛋白原与纤维蛋白的作用相似,放线菌酮与放线菌素D均可抑制纤维蛋白上调GEC表达tPA,uPA与PAI的作用,纤维蛋白平板法显示,纤维蛋白对GEC PA／PAI系统的综合效应是以升高PA活性为主,其活性能够被抑肽酶完全阻断。结论：肾脏局部毛细血[管内沉积的纤维蛋白可能通过对GEC PA／PAI系统的调节发挥其病理作用。     

人精子tPA和PAI-1的测定及精子上tPA的定位研究

目的 :人精子上组织型纤溶酶原原激活因子 (tPA)的分布及精子中tPA、纤溶酶激活物抑制因子 (PAI 1)活性研究。　方法 :应用底物显色法测定 6 1例人精子中tPA及其PAI 1的活性 ,其中正常对照组 2 0例 (已婚生育男子 ,经 2次精液分析正常者 ) ,少弱畸精症组 41例 ;用免疫组化法进行精子表面膜上tPA定位分析。　结果 :正常对照组精子中tPA和PAI 1的活性分别为 (0 2 4± 0 0 4)IU/ 10 6精子和 (0 2 3± 0 0 3)AU/ 10 6精子 ,少弱畸精症组的tPA和PAI 1活性分别为 (0 12± 0 0 3)IU/ 10 6精子和 (0 35± 0 0 9)AU/ 10 6精子 ,经分析二者之间有极显著差异 (P <0 0 1) ;tPA主要分布在精子的顶体膜、赤道板、颈部和尾部。　结论 :正常健康人精子中的tPA和PAI 1活性有别于弱精症者 ,提示精子上的tPA和PAI 1活性可能与精子活力、精子形态以及精子数有关 ;精子的顶体膜、赤道板、颈部及尾部存在着tPA ,推测其与精子运行、获能等有关。     

肾病综合征患者血浆中t-PA/PAI-1的变化及糖皮质激素治疗的影响

目的:探讨肾病综合征患者糖皮质激素治疗前后不同阶段组织型纤溶酶原激活物(t-PA)与纤溶酶原激活物抑制物-1(PA1-1)的变化.方法:分为健康对照组、肾病综合征组,采用酶联免疫吸附(ELISA)方法检测血浆中t-PA和PAI-1水平的变化.结果:t-PA的血浆水平在各组之间无统计学差异(P>0.05);PAI-1的水平在肾病综合征组较正常明显升高(P<0.05),激素治疗1周后进一步升高(P<0.05),治疗4周后比1周组有显著下降(P<0.05),但较正常仍高(P<0.05).结论:t-PA/PAI-1平衡的紊乱,可能参与了肾病综合征的损伤机制,经糖皮质激素治疗后高凝状态短期内无明显改善.     

纤溶系统和血管再狭窄

血管重建术后再狭窄的发生率较高 ,至今仍是一个临床难题。在血管损伤后再狭窄的过程中 ,纤溶酶原激活物 /纤溶酶系统尤其是尿激酶型纤溶酶原激活物及其受体起着非常重要的作用。本文就血管再狭窄过程中的作用机制加以综述     

阿托伐他汀对糖尿病肾病患者脂蛋白（a）和纤溶酶原激活抑制物-1的影响

目的探讨阿托伐他汀对糖尿病肾病（DN）患者脂蛋白（a）[Lp（a）]、组织纤溶酶原激活物（tPA）以及纤溶酶原激活抑制物-1（PAI-1）的影响。方法60例DN患者随机分为2组，治疗组患者给予阿托伐他汀20mg每日1次睡前服用，对照组给予安慰剂，共6周，治疗前后所有患者测定血糖、肾功能、总胆固醇（TC）、甘油三脂（TG）、高密度脂蛋白-C（HDL-C）、低密度脂蛋白-C（LDL-C）、PAI-1、tPA以及尿白蛋白排泄率（UAER）进行比较。结果6周后，治疗组与对照组相比，TC、TG、LDL-C、Lp（a）、PAI-1活性及UAER下降（P〈0．05或P〈0．01），而HDLC水平和tPA活性上升（P〈0．05）。对照组治疗前后各项指标无明显变化（P〉0．05），而治疗组治疗前后上述指标有显著改变（P〈0．05或P〈0．01）。结论阿托伐他汀在降低DN患者血脂的同时，通过降低Lp（a）改善纤溶系统功能，保护受损的肾脏功能。     

Effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1(PAI-1) during surgery

Dextran is known to increase the plasminogen activation rate in vitro and to decrease the α₂-antiplasmin activity.
We decided to explore the effect of dextran on plasma tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1(PAI-1) during surgical trauma.
Thirty-one patients undergoing elective surgery were given 500 ml of 6% dextran 70. Another nine patients serving as controls were given 500 ml of a glucose-electrolyte solution. The activities of t-PA and PAI-1during surgery were determined, as was the concentration of t-PA antigen.
PAI-1activity was decreased by 19% after infusion of 250 ml of dextran. After 500 ml, the activity was reduced by 22% (both P <0.05). The activity of t-PA was increased by 43% and 29% (both P <0.05) and the antigenic amount of t-PA was increased by 18% and 15% (both P <0.05) after infusion of 250 ml and 500 ml of dextran, respectively. No changes in these variables were observed in the control patients.
It is concluded that infusion of dextran promotes fibrinolysis by enhancing plasminogen activation in patients subjected to trauma. Since elevated levels of PAI-1prior to surgery are known to predispose to deep vein thrombosis, which may form already during the operation, the effect of dextran on PAI-1described here may explain its clot preventing properties.     

External pneumatic compression does not increase urokinase plasminogen activator after abdominal surgery

External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis (DVT) by reducing stasis. There is a widely held belief that they also enhance endogenous fibrinolysis; however, recent studies of tissue plasminogen activator (the primary activator of fibrinolysis) and plasminogen activator inhibitor-1 (the primary inhibitor of fibrinolysis) failed to confirm this. The hypothesis of this study was that EPC devices increase the level of urokinase plasminogen activator (uPA), a second activator of fibrinolysis. This was a prospective trial in which 44 subjects who underwent major abdominal surgery were randomized to receive unfractionated heparin injections, thigh-length sequential EPC devices, or both for DVT prophylaxis. Prophylaxis was begun immediately before surgical incision and continued until postoperative day 5 or discharge. Venous blood samples were collected from an antecubital vein for measurement of systemic uPA levels and from the common femoral vein for measurement of regional uPA levels. Samples were collected the day before surgery, after induction of anesthesia but before surgical incision, and on postoperative days 1, 3, and 5. uPA levels (ng/mL) were measured with an enzyme-linked immunoassay. Baseline uPA levels (0.41 to 0.56 ng/mL; P >.05, analysis of variance with repeated measures) were similar among the three groups. uPA levels did not change after surgery in systemic or regional blood samples in any group. There were no significant differences in systemic or regional uPA levels in the groups treated with EPC devices relative to those treated with heparin at any time point (P >.05, analysis of variance with repeated measures). Enhancement of fibrinolysis with EPC devices remains unproven; the findings reported here suggest that effective DVT prophylaxis can only be assured when the devices are used in a manner that reduces venous stasis.     

Impaired fibrinolysis in cyclosporine-treated renal transplant patients. Analysis of the defect and beneficial effect of fish-oil.

Cyclosporine treatment has been associated with thrombotic vascular complications. We investigated the activity of the fibrinolytic system and its capacity to respond upon DDAVP stimulation in a group of 20 cyclosporine-treated patients as compared with a group of 9 azathioprine-treated patients. Furthermore, the effect of the administration of fish-oil to these patients on the endogenous fibrinolytic activity was studied in a double-blind randomized, placebo-controlled cross-over study. The cyclosporine-treated patients showed a significantly reduced plasminogen activator activity and plasmin generation response upon the infusion of DDAVP as compared with the azathioprine group. In the cyclosporine group 60% of the patients had an impaired fibrinolytic response, whereas this was found in only 11% of the azathioprine-treated patients (P < 0.05). The impairment of the endogenous fibrinolysis activity could be attributed either to a defective release of plasminogen activator from the vessel wall (67% of patients) or to high plasma levels of plasminogen activator inhibitor 1 (33% of patients). Administration of fish-oil resulted in a significant improvement of the impaired fibrinolysis in the cyclosporine group. Particularly, in patients with a defective release of plasminogen activator from the vessel wall, fish-oil treatment resulted in a normalization of the fibrinolytic activity. These results indicate that cyclosporine treatment induces an impaired fibrinolysis that may contribute to the frequent occurrence of thromboembolic complications and eventually the impairment of renal function in cyclosporine-treated patients. The beneficial effect of the administration of fish-oil on the endogenous fibrinolysis may result in a reduction of the adverse events associated with cyclosporine treatment.     

尿激酶治疗结核性包裹性胸腔积液不同时间后手术治疗的疗效分析

目的探讨尿激酶治疗结核性包裹性胸腔积液后外科手术治疗的最佳时机。方法结核性包裹性胸腔积液患者120例。依据接受手术前尿激酶治疗时间的不同将120例患者分为两组,A组60例,为常规抗结核治疗并给予胸腔注射尿激酶治疗1个月左右接受手术治疗;B组60例,为常规抗结核治疗并给予胸腔注射尿激酶治疗2个月左右接受手术治疗。比较两组患者的临床疗效。结果 A组患者手术时间为(145.72±38.48)分钟,术中出血量(332.96±108.03)ml,术后24小时引流量(264.67±101.37)ml,引流管放置时间为(4.49±1.22)天;B组患者分别为(149.14±39.06)分钟、(356.64±106.31)ml、(262.38±97.80)ml和(4.53±1.26)天,两组比较差异无统计学意义(P0.05)。A组患者的治疗总有效率、肺活量(VC)增加量和最大通气量(MVV)增加量分别为86.67%、(0.32±0.10)ml和(13.24±2.45)ml,B组患者分别为96.67%、(0.47±0.14)ml和(17.03±3.75)ml,两组比较差异有统计学意义(P0.05)。两组患者术后复发率比较,差异无统计学意义(P0.05)。A组不良反应发生率显著高于B组,两组间比较差异有统计学意义(P0.05)。结论结核性包裹性胸腔积液患者在抗结核及胸腔注射尿激酶穿刺抽液治疗2个月左右疗效改善仍不明显时,接受手术治疗可获得较好的临床效果。     

External pneumatic compression and fibrinolysis in abdominal surgery

INTRODUCTION: External pneumatic compression (EPC) devices prevent lower extremity deep venous thrombosis by increasing venous flow and thereby reducing stasis. Early studies suggested that they also enhance systemic fibrinolytic activity and thus prevent thrombus formation; more recent studies have been conflicting. The hypothesis of this study was that EPC devices enhance systemic fibrinolysis or reduce postoperative fibrinolytic impairment in patients undergoing abdominal surgical procedures. METHODS: Each of 48 patients (98% male; mean age, 67 years) undergoing major intra-abdominal surgical procedures (36 bowel procedures, 12 aortic reconstructions) was prospectively randomized to one of three treatments for deep venous thrombosis prophylaxis: subcutaneous heparin injections (HEP group), use of a thigh-length sequential EPC device (EPC group), or both (HEP + EPC group). Antecubital venous samples were collected for measurement of systemic fibrinolytic activity on the day before surgery, after induction of anesthesia but before prophylaxis was initiated, and on postoperative days 1, 3, and 5. Fibrinolysis was assessed through measurement of the activities of the rate limiting fibrinolytic activator, tissue plasminogen activator, and its inhibitor plasminogen activator inhibitor-1 with amidolytic methods. RESULTS: On the day before surgery, plasminogen activator inhibitor-1 activity was elevated in all groups in comparison with that in age-matched and sex-matched controls (20.3 +/- 0.6 AU/mL). In the HEP group, plasminogen activator inhibitor-1 activity was further elevated above the value for the day before surgery on postoperative day 1 (28.5 +/- 4.3 AU/mL; P =.04) and postoperative day 3 (25.1 +/- 1.9 AU/mL; P =.07). No significant decrease in plasminogen activator inhibitor-1 activity occurred in either group treated with EPC devices in comparison with the HEP group at any time. There were no changes in tissue plasminogen activator activity postoperatively in the HEP group and no significant increases in either EPC group at any point. CONCLUSIONS: Reduced systemic fibrinolytic activity ("fibrinolytic shutdown") occurred in these patients after abdominal surgery; it was manifested as increased plasminogen activator inhibitor-1 activity. EPC devices did not enhance systemic fibrinolysis or prevent postoperative shutdown either by decreasing plasminogen activator inhibitor-1 activity or by increasing tissue plasminogen activator activity. These data suggest that EPC devices do not prevent deep venous thrombosis by fibrinolytic enhancement; effective prophylaxis is achieved only when the devices are used in a manner that reduces lower extremity venous stasis.     

联合转染tPA基因和PCNA反义寡核苷酸抑制兔自体移植动脉再狭窄研究

目的研究血管局部联合转染组织型纤溶酶原激活物（tPA）基因和增殖细胞核抗原反义寡核苷酸（PCNA—ASODN）对自体移植动脉血管再狭窄的防治作用。方法120只新西兰雄性白兔，按数字表法随机均分为4组（对照组、PCNA—ASODN组、tPA组、tPA＋PCNA—ASODN组）。将同一只兔的左、右髂外动脉（各1、0cm长）对换移植，移植血管及吻合口缝线分别用pBudCE4．1／tPA和PCNA-ASODN液浸泡。于术后3、7、14、28及56d取移植血管制片，显微镜下观察内膜增生情况，计算机图像分析测量其内膜面积和移植血管狭窄率，扫描电镜观察移植血管壁血栓形成情况，并分别用RT—PCR和免疫组织化学染色法检测tPA基因的mRNA表达率与PCNA阳性细胞百分率。结果术后3、7、14和28d时，tPA组与tPA＋PCNA-ASODN组的tPA基因mRNA表达率明显高于另2组（P〈0．01），PCNA—ASODN组、tPA组和tPA＋PCNA—ASODN组PCNA阳性细胞百分率均明显低于对照组（P〈0．05，P〈0、01）。tPA＋PCNA—ASODN组和PCNA—ASODN组、tPA组各时相血管壁内膜增生比对照组明显减轻，内膜面积和管腔狭窄程度显著低于对照组（P〈0、05．P〈0．01），且tPA＋PCNA—ASODN组又明显低于另2组（P〈0．05）。扫描电镜观察显示，tPA组和tPA＋PCNA-ASODN组血管壁只见少量血小板附着，未见血栓形成，而对照组血管壁可见大量血小板附着，且有血栓形成。结论血管局部联合转染tPA基因和PCNA—ASODN能有效抑制VSMC增殖和血栓形成，阻止内膜增生，防止移植血管狭窄。     

Initiation of a fibrinolytic system in hepatic resection: The roles of tissue-type plasminogen activator and plasminogen activator inhibitor-1

The factors related to the initiation of fibrinolysis, especially with regard to the tissue-type plasminogen activator (tPA) and the plasminogen activator inhibitor-1 (PAI-1), were investigated in 15 patients who underwent hepatic resection, and the findings were compared between those with normal livers and those with diseased livers. It was found that tPA increased before hepatic division, whereas PAI-1 increased after hepatic division and reached a peak immediately following the operation. Plasminogen decreased during hepatectomy, reaching its lowest point on postoperative day 1, and increasing later. Decreased levels of both plasminogen and the ₂-plasmin inhibitor were considered to be partly due to plasmin formation in the blood. Patients with a diseased liver tended to have higher intraoperative values of euglobulin lysis activity and higher postoperative values of plasminogen activator, but significantly lower postoperative values of ₂-plasmin inhibitor than those with a normal liver. The results of this study suggest that activation of the fibrinolytic system occurs both during hepatectomy and in the early postoperative period, and that patients with a diseased liver are prone to develop hyperfibrinolysis during hepatectomy. Moreover, the increased levels of both tPA and PAI-1 can serve as one of the most sensitive markers for the vital reaction against surgical stress.