组织纤溶酶原激活物和纤溶酶原激活物抑制剂-1与腹腔镜手术的关系

组织纤溶酶原激活物（t-PA）和纤溶酶原激活物抑制剂-1（PAI-1）是纤溶系统的重要组成部分,传统开腹手术,t-PA与PAI-1之间的平衡被打破,导致术后腹腔粘连及血栓形成.腹腔镜手术对人体创伤小,对腹膜刺激少,因此,对t-PA和PAI-1之间的平衡影响减小,术后粘连及血栓形成的发生率及程度也随之降低.本文综述了t-PA和PAI-1与腹腔镜手术方面的研究进展.     

组织纤溶酶原激活物和纤溶酶原激活物抑制剂-1与腹腔镜手术的关系

组织纤溶酶原激活物(t-PA)和纤溶酶原激活物抑制剂-1(PA I-1)是纤溶系统的重要组成部分,传统开腹手术,t-PA与PA I-1之间的平衡被打破,导致术后腹腔粘连及血栓形成。腹腔镜手术对人体创伤小,对腹膜刺激少,因此,对t-PA和PA I-1之间的平衡影响减小,术后粘连及血栓形成的发生率及程度也随之降低。本文综述了t-PA和PA I-1与腹腔镜手术方面的研究进展。     

内蒙古地区汉族IgA肾病患者PAI-1基因多态性与临床病理特征的关系

目的:研究影响内蒙古地区汉族IgA肾病患者PAI-1基因多态性与临床病理特征的关系。方法:采集100例肾活检证实的IgA肾病患者血样,提取基因组DNA。用等位基因特异聚合酶链反应(ASPCR)法进行PAI-14G/5G基因型分析。分别分析各基因型与IgA肾病患者的临床特征、病理类型的关系。结果:IgA肾病组的4G/4G基因型发生频率(41%)显著高于对照组(23%,P值<0.01)。血尿的分级水平在4G/4G基因型患者中显著高于4G5G或5G5G基因型患者(χ2=6.71,P<0.05)。PAI-1基因型频率和等位基因频率与IgA肾病的病理Hass分级无关(P>0.05),伴肾小球硬化组的4G/4G基因型频率显著高于不伴肾小球硬化组(P<0.05)。结论:PAI-14G/4G基因型是内蒙古地区汉族IgA肾病患者发病的易感基因型,除血尿的分级水平外PAI-1基因的三种基因型的临床特征差异无统计学意义。PAI-1基因4G/5G多态性与IgA肾病肾小球硬化显著相关,而与其病理Hass分级无关。     

纤溶酶原激活物抑制物-1与糖尿病肾病关系的研究进展

糖尿病肾病(diabetic nephropathy,DN)是糖尿病(diabetes mellitus,DM)最常见的慢性并发症之一.细胞实验、动物实验、临床研究均证实纤溶酶原激活物抑制物-1(Plasminogen activator inhibitor1.PAI-1)是其重要的致病因素之一.糖尿病(DM)情况下,高血糖、血管紧张素Ⅱ(Angiotensin Ⅱ,Ang Ⅱ)、转化生长因子-β1(transforming growth factor-β1,TGF-β1)、非酶促糖基化终末产物(advanced glycation endoproducts,AGEs)和醛固酮的水平升高等均可上调全身和肾脏局部的PAI-1表达,导致肾小球、肾间质纤维化和肾小管损害,促进DN的发生发展.血管紧张素转化酶抑制剂(ACEI)和血管紧张素Ⅱ受体阻断剂(ARB)、噻唑烷二酮类(thiazolidinediones,TZDs)、双胍类、调脂药、醛固酮受体拮抗剂和抗氧化剂等药物可不同程度阻断上述途径,从而有助防止、延缓DN的发展.     

内蒙古汉族IgA肾病临床病理与肿瘤坏死因子β基因多态性的关系

IgA肾病（IgAN）是一种多基因病,其发病可能与HLA连锁的某些基因（HLA-DR4、A、B、DQ）有关。肿瘤坏死因子（TNF）位于HLA-Ⅲ抗原基因簇内,因此TNF基因可能是IgA肾病的易感基因。本研究分析IgA肾病患者临床特征与TNF-β基因多态性的关系,了解内蒙古地区汉族TNF-β基因多态性与IgA肾病各种病理类型的关系。     

MYH9基因多态性与汉族 IgA 肾病病理关系的研究

目的：探讨 MYH9基因多态性与汉族 IgA 肾病病理的关系。方法：经肾组织活检确诊的 IgA 肾病患者148例作为研究对象,取外周血提取 DNA,采用限制性片段长度多态性分析（PCR - RFLP）法检测 MYH9基因 Rs3752462基因多态性,研究其与 IgA 肾病病理的相关性。结果：（1）Rs3752462位点群体符合哈温平衡;（2）Rs3752462位点基因型与病理 HASS分级差异无统计学意义。结论：MYH9基因 Rs3752462位点基因多态性与 IgA 肾病病理无明显相关性。     

纤溶酶原激活物抑制物1和糖尿病肾病研究进展

随着糖尿病肾病的发病率明显升高,糖尿病肾病的发病机制日益受到关注.本文着重对纤溶酶原激活物抑制物1在糖尿病肾病患者中的升高机制、在糖尿病肾病发展中的作用及针对性治疗进行综述.     

TNFα、β基因多态性对内蒙古汉族IgA肾病患者的预后影响

目的：研究TNFα、β基因多态性对内蒙古汉族IgA肾病患者的预后影响。方法：选100例内蒙古汉族IgA肾病患者（对其中33例患者进行1月～60月的随访）及105例正常对照组,采用聚合酶链式反应-限制性片段长度多态性分析（PCR-RFLP）技术检测TNFα、β基因多态性,分析不同基因型与IgA肾病临床特征、病理类型及预后的关系。结果：（1）IgA肾病患者TNFα、β的3种基因型与健康对照组间差异无统计学意义（P〉0.05）。（2）IgA肾病患者的TNFβ2等位基因频率（63.5%）较正常人（54.3%）升高（χ2=1.83,P〈0.01）。（3）TNFα、β的3种基因型与IgA肾病患者的年龄、血压、血尿、尿蛋白、肾功能及病理间无显著关系。（4）相对于其他基因型,TNFα1/1基因型在进展组高于非进展组,P=0.04〈0.05。结论：（1）TNFβ2等位基因频率与IgA肾病发病易患性相关。（2）TNFα1/1基因型可能是IgA肾病慢性化进展的危险因子之一。     

不同病理类型成人肾病综合征患者血清可溶性尿激酶型纤溶酶原激活物受体水平及意义

目的:检测可溶性尿激酶型纤溶酶原激活物受体(suPAR)在肾病综合征患者血清中的水平,结合临床资料及肾活检病理分型分析其临床意义。方法:将70例肾病综合征患者根据肾活检病理类型分为膜性肾病组(MN)、糖尿病肾病组(DN),微小病变性肾小球病组(MCD),局灶节段性肾小球硬化症(FSGS)组及正常对照组,采用酶联免疫吸附试验法分别检测血清suPAR水平,比较不同组别suPAR水平的变化,并分析与临床参数之间的关系。结果:FSGS、MCD、MN和DN组肾病综合征患者血清suPAR水平明显高于正常对照组(P0.001),FSGS组和MN组血清suPAR水平显著高于MCD组(P=0.013,P=0.029),而FSGS组和MN组血清suPAR水平差异无统计学意义;血清suPAR水平与年龄、血肌酐、尿素氮、免疫球蛋白IgA、免疫球蛋白Ig G呈正相关(rs=0.401 P=0.001;rs=0.286,P=0.016;rs=0.249,P=0.037;rs=0.245,P=0.041;rs=0.247,P=0.039),与eGFR、血红蛋白、血小板呈负相关(rs=-0.265,P=0.026;rs=-0.237,P=0.048;rs=-0.309,P=0.009)。结论:FSGS组血清suPAR水平显著高于MCD组,有望成为区别FSGS与MCD的生物标志物。     

纤溶酶原激活物抑制因子Ⅰ对肾病患者肾纤维蛋白沉积的影响

已知肾内纤维蛋白沉积在抗-GBM肾炎和弥漫性血管内凝血所致的肾功能衰竭中起重要作用。人类肾小球纤维蛋白沉积多见于肾皮质坏死、溶血性尿毒综合症、毛细血管外肾炎和肾移植超急性排异反应。肾小球血管内或球囊腔纤维蛋白沉积的持续存在,可能由于局部细胞纤维蛋白溶解作用的减退所致。为解释这些发现并研究纤维蛋白溶解障碍,作者应用免疫荧光技术对血管性肾病和毛细血管外肾炎患者的肾活检标本进行了研究。方法与结果28例各种肾病患者,男18例,女10例,年龄5～78岁。肾组织标本除4例正常标本中的3例外,均来自经皮针吸肾活检;3例中1例来自肾癌肾切除的肾脏标本;另2例为因血管或泌尿原因而不宜行     

肌球蛋白重链9基因单核苷酸多态性与内蒙古自治区汉族IgA肾病临床、病理及预后的关系

目的 探讨肌球蛋白重链(MYH)9基因单核苷酸多态性与内蒙古自治区汉族IgA肾病患者临床特征、病理及预后的关系.方法 以经肾组织活检确诊的IgA肾病患者148例为研究对象,对其中56例患者进行了1～97月的随访.取外周血提取DNA,采用PCR限制性片段长度多态性分析(RFLP)法检测MYH9基因Rs3752462、Rs4821480位点单核苷酸多态性.研究各位点基因型与IgA肾病患者临床特征的相关性.分析不同基因型与疾病进展和预后的关系.结果 (1)Rs3752462位点符合Hardy-Weinberg平衡,Rs4821480位点不符合Hardy-Weinberg平衡.(2)IgA肾病患者MYH9基因Rs3752462位点TT基因型患者的收缩压低于CC+CT基因型(P＜0.05).Rs4821480位点GG基因型与TT+GT基因型两组患者收缩压、舒张压、年龄差异有统计学意义(P＜0.05).Scr、肌酐清除率、血白蛋白、血红蛋白、镜下血尿、蛋白尿程度等临床指标及病理HASS分级、肾病理改变在Rs4821480位点、Rs3752462位点3种基因型组间差异无统计学意义.(3) Kaplan-Meier生存分析提示Rs3752462位点CC基因型、Rs4821480位点TT基因型患者肾活检到肾功能减退时间显著较短(P＜0.05).结论 MYH9基因Rs3752462位点C等位基因是引起IgA肾病患者高血压损害的独立危险因素.MYH9基因Rs4821480位点3种基因型多态性与患者预后相关.携带Rs3752462位点C等位基因、Rs4821480位点T等位基因可能影响患者的预后.     

Atherosclerosis is associated with plasminogen activator inhibitor type-1 in chronic haemodialysis patients

Aim: The aim of the present report was to investigate the probable association of circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls with atherosclerotic disease in chronic haemodialysis (HD) patients. Methods: Sixty-eight non-diabetic HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. Levels of serum PAI-1, C-reactive protein (CRP), interleukin (IL)-6 and lipids profile were measured. Internal iliac artery samples were obtained at the time of renal transplantation. Quantitative expression of PAI-1 in internal iliac artery walls was assessed by positive unit (pu) value using an immunohistochemical method. In addition, the IMT and carotid plaque score were analyzed in relation to circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls. Results: Compared with control subjects, HD patients had significantly increased common carotid artery (CCA)-IMT (P = 0.002). Atherosclerotic plaques were detected in 42 (61.76%) of HD patients and in two (4%) controls. The above ultrasonographic indices were correlated with age in HD patients (P < 0.001). A significant relationship was observed between IMT and systolic blood pressure (BP), low-density lipoprotein in HD patients (P < 0.001 and P < 0.001, respectively). In HD patients, IMT was significantly correlated with CRP and IL-6 (P < 0.001 and P < 0.001, respectively). In HD patients, a close correlation was found between serum PAI-1 level, CRP and IL-6 (P < 0.01 and P < 0.01, respectively). A close correlation was also found between PAI-1 pu value, CRP and IL-6 (P < 0.01 and P < 0.01 respectively). Serum PAI-1 level is highly correlated to PAI-1 pu value (P < 0.01). In HD patients, CCA-IMT and plaque score were correlated significantly with circulating levels of PAI-1(P < 0.01 and P < 0.05, respectively) and expression of PAI-1 in internal iliac artery walls (P < 0.01 and P < 0.05, respectively). Multivariate analysis showed that log CRP values were a strong independent contributor to CCA-IMT and plaque score (P = 0.03 and P = 0.04, respectively). Multivariate analysis showed that serum PAI-1 concentration was a strong independent correlate of CCA-IMT and carotid plaque score (P = 0.004 and P = 0.009, respectively). Multivariate analysis also showed that expression of PAI-1 in internal iliac artery walls was a strong independent correlate of CCA-IMT and carotid plaque score (P = 0.008 and P = 0.005, respectively). Conclusion: The circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls were statistically associated with CRP, IL-6 and low-density lipoprotein cholesterol. Moreover, in HD patients, CCA-IMT and plaque score were correlated significantly with circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls and the circulating levels of PAI-1 and expression of PAI-1 in internal iliac artery walls were independent predictors of carotid atherosclerosis including CCA-IMT and carotid plaque score. The correlations may suggest that increased circulating PAI-1 level and upregulated expression of PAI-1 in the vasculature could indicate a chronic endothelium activated state and PAI-1 may more precisely identify the risk of atherothrombosis and be useful as a target for anti-inflammatory treatment strategies.     

Ⅰ型纤溶酶原激活物抑制物在IgA肾病肾小管间质损伤中的作用研究

目的 探讨Ⅰ型纤溶酶原激活物抑制物（ＰＡＩ－１）在ＩｇＡ肾病肾小管间质损害中的作用。方法 采用原位杂交和免疫组织化学技术,分别在基因和蛋白质水平检测３８例ＩｇＡ肾病患者肾小管间质中的ＰＡＩ－１表达,同时观察α－平滑肌肌动蛋白和增殖细胞核抗原（ＰＣＮＡ）的表达变化。     

Association of plasminogen activator inhibitor-1 gene polymorphism and type 2 diabetic nephropathy

Background: We investigated the relationship between plasminogen activator inhibitor-1 (PAI-1) 4G/5G insertion/deletion polymorphism and prevalence of diabetic nephropathy (DN) in Chinese patients. Methods: A total of 107 patients with type 2 diabetes were randomly recruited in the study, and 102 healthy subjects were selected as Control. Patients were divided into three groups according to their urinary albumin–creatinine ratio (UACR). Group A (n?=?44), had patients without DN (serum creatinine <106?µmol/L and UACR <30?µg/mg); Group B (n?=?30), had patients with micro-albuminuria (UACR 30–299?µg/mg), and Group C (n?=?33), had patients with macro-albuminuria (UACR ≥300?µg/mg and creatinine <200?µmol/L). Plasma level of PAI-1 was measured by ELISA. PAI-1 polymorphism was determined by a polymerase chain reaction (PCR) method and DNA sequencing. Results: (1) The plasma PAI-1 levels of group A (60.39?±?17.01?ng/L), group B (68.76?±?17.81?ng/L) and group C and (68.63?±?18.30?ng/L) are higher than that of controls (46.26?±?26.04?ng/L); (2) Patients with genotype 4G/4G tended to exhibit higher PAI-1 level; (3) The distribution frequency of genotype 4G/4G in group C was significantly higher than in group A (42.4% vs. 28.7%, p?Conclusions: (1) Plasma PAI-1 level was elevated in Type 2 diabetic patients; (2) The level of plasma PAI-1 is closely related to PAI-1 gene 4G/5G polymorphism and (3) PAI-1 4G/5G polymorphism is associated with the development and progression of predominant proteinuria diabetes nephropathy.     

Preoperative plasma plasminogen activator inhibitor type-1 and serum C-reactive protein levels in patients with colorectal cancer

Background: Preoperative plasma plasminogen activator inhibitor-1 (PAI-1) is a prognostic variable in patients with colorectal cancer. It has been suggested, however, that plasma PAI-1 is a nonspecific prognostic parameter similar to the acute-phase reactant C-reactive protein (CRP). In the present study we analyzed the association between plasma PAI-1 and serum CRP in patients scheduled for elective resection of colorectal cancer. In addition, the prognostic value of PAI-1 and CRP was studied in this patient cohort. Methods: PAI-1 and CRP were analyzed in citrated plasma and serum, respectively, obtained preoperatively from 594 patients. Patients who required preoperative blood transfusion received SAGM blood, in which soluble PAI-1 is not present. None of the patients received pre- or postoperative adjuvant chemotherapy, and all were followed in the outpatient clinic for at least 5 years or until death. The association of PAI-1 and CRP, respectively, with survival was tested using the median value of PAI-1 and the upper normal limit for CRP. Analyses were performed by inclusion of all patients, and in the subgroup of patients, who underwent curative resection. Results: The median follow-up period was 6.8 (5.4–7.9) years. The median value of plasma PAI-1 was 35.8 ng/ml, and values greater than 94 nmol/L identified patients with increased CRP levels. Comparison of the molecules showed that PAI-1 was weakly correlated with CRP (r=.26;P<.0001). Both molecules showed a Dukes independent distribution. In univariate survival analyses high levels of PAI-1 were found associated with poor prognosis and low levels with good prognosis (P=.02, HR: 1.3). Similarly, high levels of CRP were found associated with poor prognosis and low levels with good prognosis (P<.0001, HR: 1.9). In a multivariate statistical analysis including Dukes classification, gender, age, tumor location, perioperative blood transfusion, PAI-1 and CRP, plasma PAI-1 was a dependent prognostic variable, while serum CRP (P<.0001; HR: 1.4; 95% CI: 1.3–1.5) was found to be a Dukes independent prognostic variable. Similar analyses, excluding patients with Dukes’ D disease showed serum CRP to be an independent prognostic variable (P<.0001; HR: 1.3: 95% CI: 1.2–1.5). Conclusions: This study did not show a strong correlation between plasma PAI-1 and serum CRP in patients with colorectal cancer. Serum CRP was found to be a Dukes independent prognostic variable in this patient cohort, and was found to identify a subgroup of curatively resected patients at risk for short survival. The study received financial support from The Ingeborg Roikjer Foundation, The Aage and Johanne Louis-Hansen Foundation, The Danish Pharmacy Foundation of 1991, The Agnete and Poul Friis Fund, The Walter and O. Kristiane Christensen Fund, The E. Danielsen Family Fund, The Hede-Nielsen Foundation, The Einar and Vera Hansen Foundation, The Torben and Alice Frimodt Fund, and The Danish Cancer Society (grant # 97 100 21).     

Close relationship of plasminogen activator inhibitor-1 4G/5G polymorphism and progression of IgA nephropathy

BACKGROUND: The plasminogen activator inhibitor-1 (PAI-1) 4G/4G genotype influences the development of diabetic nephropathy and lupus nephritis. However, the association of the PAI-1 4G/4G genotype and IgA nephropathy (IgAN) has not been investigated. SUBJECTS AND METHODS: The PAI-1 and ACE polymorphisms were examined in 270 healthy volunteers and 202 biopsy-proven IgAN patients, including 117 untreated IgAN patients who had an annual health check, allowing an estimation of the time of onset of overt proteinuria and/or hematuria. The relationship between the gene polymorphisms and the pathogenesis of IgAN were examined in 202 IgAN patients and the relationship between the gene polymorphisms clinical and pathohistological findings were examined in 117 untreated IgAN patients cross-sectionally at the time of renal biopsy. RESULTS: 202 IgAN patients and 117 untreated IgAN patients did not have different frequencies in PAI-1 4G/5G (4G/4G : 4G/5 : 5G/5G = 82 : 90: 30, 45 : 55 : 17) and ACE I/D (DD : ID : II = 41 : 82 : 79, 21 : 54 : 42) gene polymorphisms compared with 270 healthy volunteers (4G/4G : 4G/5 : 5G/5G = 99 : 124 : 47, DD : ID : II = 53 : 106 : 111). However, IgAN with 4G/4G had significantly more advanced histological changes than IgAN with 4G/5G or 5G/5G both in glomerular and tubulointerstitial findings (p < 0.0005). The disease duration in IgAN with 4G/4G was shorter than in IgAN with 4G/5G + 5G/5G (6.22 +/- 6.38 and 8.80 +/- 9.79 years, respectively, p < 0.05). Creatinine clearance (Ccr) in IgAN with 4G/4G was significantly lower than IgAN with 4G/5G or 5G/5G (72.3 +/- 26.5 and 82.4 +/- 22.8 ml/min, respectively, p < 0.05). The mean urinary protein excretion in IgAN with 4G/4G was significantly more than in IgAN with 4G/5G or 5G/5G (1.10 +/- 1.48 and 0.70 +/- 1.01 g/day, respectively, p < 0.05). There was no difference between IgAN with the DD ACE genotype and IgAN with ID + II genotypes in either the clinical or histopathological findings. CONCLUSION: PAI-1 polymorphism is not associated with genesis of IgA nephropathy, but may be a risk factor for the progression of IgA nephropathy in Japanese.     

Association of interleukin-1 receptor antagonist gene polymorphism with IgA nephropathy

It is evident that cytokines play an important role in the pathogenesis as well as disease progression of IgA nephropathy (IgAN). Several gene polymorphisms of the pertinent cytokines have an influence on the level of cytokine production. Interleukin-1 receptor antagonist (IL-1ra) gene polymorphism has been found to affect disease susceptibility and activity in several inflammatory diseases. In the present study, we analyzed polymorphism of the variable number tandem repeat (VNTR) of IL-1ra in patients diagnosed as having IgAN (n = 106) and normal controls (n = 74). The allele frequency of IL-1ra polymorphism in IgAN patients was not statistically different from that of the control group. There was no significant difference in the carriage rate of the two-repeat allele (IL1RN*2) between IgAN patients and the control group (8.5 vs. 6.8%). The carriage rate of IL1RN*2 was significantly higher in IgAN patients with severe proteinuria (>or=1.6 g/day) or increased serum creatinine level (>or=2.0 mg/dl; p < 0.05). Furthermore, the carriage rate of IL1RN*2 was significantly higher in patients with severe mesangial cell proliferation (p < 0.01). Our results suggest that IL-1ra polymorphisms are not associated with the development of IgAN in Japanese patients but the presence of IL1RN*2 may be associated with increased disease activity.