Improvement effect of estradiol valerate combined with aspirin on intrauterine adhesion in rats / 吉林大学学报(医学版)

Objective:To investigate the improvement effect of estradiol valerate combined with aspirin on the intrauterine adhesion (IUA) in the rats, and to elucidate the therapeutic mechanism of estradiol valerate combined with aspirin. Methods:Fifty healthy female SD rats were randomly divided into control group, model group, estradiol valerate group, aspirin group,and estradiol valerate combined with aspirin group (combination group)(n=10);the rats in the other groups except control group were used to establish the IUA models with double injury method of uterine curettage and infection. The serum and uterine tissue were taken from the rats in each group 24 h after continuous administration, the estradiol levels in serum of the rats were observed by ELISA, and the pathological changes and the number of glands in the uterine cavity of the rats in various groups were observed by HE staining, and the ratio of endometrial fibrosis are a was observed by Masson staining. The expression levels of transforming growth factor-β1 (TGF-β1), plasminogen activator inhibitor type-1 (PAI-1) and matrix metalloproteinase-9 (MMP-9) in the endometrium of the rats were detected by immunohistochemistry. Results:The results of ELISA indicated that the estrodiol level in serum of the rats in model group was significantly lower than that in control group(P<0.05);compared with model group,the estrodiol levels in serum of the rats in estradiol valerate group, aspirin group, and combination group were significantly increased (P<0.05). The results of HE and Masson staining showed that compared with control group, uterine cavity adhesion and enlargement, fluid accumulation in the cavity, disorganized arrangement of the cells of uterine cavity wall, significant infiltration of inflammatory cells, endometrial stroma fibrosis,and disordered collagenous fibers were found in model group; the number of endometrial glands in the rats was significantly decreased(P<0.05),and the fibrosis area ratio was significantly increased (P<0.05). Compared with model gorup,the adhesion and effuson in uterine cavity,inflammatory cell infiltration and endometrial stroma fibrosis were alleviated,the cells of uterine cavity wall were arranged neatly,and there was little collagenous fibers in estradiol valerate group,aspirin group,and combination group;the number of endometrial glands was increased(P<0.05),and the fibrosis area ratios were significantlhy decreased(P<0.01).Compared with aspirin group,the number of endometrial glands in combination group was significantly increased(P<0.05),and the fibrosis area ratio was significantly decreased(P<0.05).Compared with model group, the expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in estradiol valerate group, aspirin group, and combination group were significantly decreased (P<0.05 or P<0.01), and the expression levels of MMP-9 protein in the endometrium tissue were significantly increased (P<0.05).The expression levels of TGF-β1 and PAI-1 proteins in the endometrium tissue of the rats in combination group were significantly lower than those in aspirin group (P<0.05), and the expression level of MMP-9 in the endometrium tissue was significantly higher than that in aspirin group (P<0.05). Conclusion:Estradiol valerate combined with aspirin can decrease the expression levels of TGF-β1 and PAI-1 in the endometrium tissue and increase the expression level of NMP-9, which can improve the IUA of the rats.

Relationship between plasminogen activator inhibitor type-1 (PAI-1) gene polymorphisms and osteoporosis in Turkish women

OBJECTIVE: The development of osteoporosis is associated with several risk factors, such as genetic structures that affect bone turnover and bone mass. The impact of genetic structures on osteoporosis is not known. Plasminogen activator inhibitor type-1 regulates the bone matrix and bone balance. This study assessed the correlation between plasminogen activator inhibitor type-1 gene 4G/5G polymorphisms and osteoporosis in a population of Turkish women. METHODS: A total of 195 postmenopausal female patients who were diagnosed with osteoporosis (Group I) based on bone mineral density measurements via dual-energy x-ray absorptiometry and 90 females with no osteoporosis (Group II) were included in this study. Correlations between PAI-1 gene 4G/5G polymorphisms and osteoporosis were investigated through the identification of PAI-1 gene 4G/5G polymorphism genotypes using the polymerase chain reaction. RESULTS: No significant differences in the genotype and allele frequency of 4G/5G plasminogen activator inhibitor type-1 polymorphisms were observed between the two groups, and both groups exhibited the most frequently observed 4G5G genotype. CONCLUSION: No correlation between the development of osteoporosis in the female Turkish population and 4G/5G plasminogen activator inhibitor type-1 gene polymorphisms was observed.

Effect of plasminogen activator inhibitor type-1 on transforming growth factor-beta 1 , hyaluronic acid and tissue inhibitor Of metalloproteinase-1 of hepatic stellate cells / 中国综合临床

Objective To study the effect of plasminogen activator inhibitor type-1 ( PAI-1 ) on the protein expression of transforming growth factor-beta 1 ( TGFβ1 ), hyaluronic acid ( HA ) and tissue inhibitor of metalloproteinase-1 (TIMP-1) of hepatic stellate cells(HSC). Methods Methyl thiazolyl tetrazolium (MTT)was performed to detect the effect of PAI-1 on the proliferation of LX-2 ,and to determine the perfect intervention concentration of PAI-1. After incubation with PAI-1 in LX-2 culture solution for 12 h,24 h,48 h,the protein expression of TGFβ1 ,TIMP-1 and HA was observed with enzyme linked immunosorbent assay (ELISA). Results A492 in the negative control was 0. 473 ± 0. 353, and 1. 249 ± 0. 440, 1. 636 ± 0. 315,1.283 ± 0. 413,0. 938 ±0. 263 and 0. 303 ±0. 125 when the concentration of PAI-1 was 5,10,20,40 and 80 μg/L,respectively,a concentration of 10 μg/L of PAI-1 showed the strongest stimulation remarkablely ( F = 11. 697, P ＜ 0. 01 ).After incubation with PAI-1 for 12 h,24 h,48 h,the protein expression of HA,TGFβ1 and TIMP-1 in the LX-2 supernatant significantly increased compared to negative control (F = 1566. 752,235. 632 and 67. 359,respectively,P ＜ 0. 01 or ＜ 0. 05 ). Conclusion PAI-1 may influence the development of hepatic fibrosis through promoting the protein expression of HA ,TGFβ1 and TIMP-1 of HSC.

Atividade pró-trombótica da toxina ExoU de Pseudomonas aeruginosa detectada em modelos experimentais in vivo e in vitro / Prothrombotic activity of the Pseudomonas aeruginosa toxin ExoU detected in experimental models in vivo and in vitro

Pseudomonas aeruginosa é um importante agente de pneumonia, particularmente em pacientes submetidos à ventilação mecânica, que pode evoluir para sepse, com elevadas taxas de letalidade. Na sepse, o processo inflamatório sistêmico exacerbado favorece o desequilíbrio entre as vias de coagulação e fibrinólise e a instalação de um estado pró-coagulante, com o aparecimento de trombose microvascular, coagulação intravascular disseminada e falência de múltiplos órgãos. Conhecendo a potente atividade pró-inflamatória da toxina ExoU produzida por P. aeruginosa, decorrente de sua atividade fosfolipásica A2, o objetivo desta tese foi investigar seu potencial de indução de alterações hemostáticas relacionadas à patogênese da sepse. Utilizando modelo de sepse em camundongos inoculados, por via intratraqueal, com suspensões de P. aeruginosa produtora de ExoU (PA103) ou de cepa com deleção do gene exoU, não produtora da toxina, foi mostrado que ExoU determinou maior gravidade da infecção, maior taxa de letalidade, leucopenia, trombocitose, hiperpermeabilidade vascular e transudação plasmática, evidenciadas, respectivamente, pela maior concentração de proteínas nos lavados broncoalveolares (LBAs) e acúmulo do corante Azul de Evans, previamente inoculado nos animais, por via endovenosa, no parênquima renal. ExoU favoreceu, também, a ativação plaquetária, confirmada pela maior concentração de plaquetas expressando P-seletina em sua supefície, maior número de micropartículas derivadas de plaquetas e maior concentração plasmática de tromboxano A2. A histopatologia dos pulmões e rins dos animais infectados com PA103 confirmou a formação de microtrombos, que não foram detectados nos animais controles ou infectados com a cepa mutante. Nos pulmões, a produção de ExoU determinou intensa resposta inflamatória com maior concentração de leucócitos totais e polimorfonucleados, interleucina-6 e fator de necrose tumoral-alfa nos LBAs. A análise imunohistoquímica mostrou intensa deposição...

Pseudomonas aeruginosa is an important agent of pneumonia, mainly in patients undergoing mechanical ventilation, which can progress to sepsis with high mortality rates. In sepsis, the systemic inflammatory process favors exacerbated imbalance between the coagulation and fibrinolysis pathways and the installation of a procoagulant state, leading to microvascular thrombosis, disseminated intravascular coagulation and multiple organ failure. Knowing the powerful proinflammatory activity of the P. aeruginosa toxin ExoU, secondary to its phospholipase A2 activity, the goal of this study was to investigate the ExoU potential to induce hemostatic changes related to sepsis pathogenesis. By using a murine model of pneumosepsis, obtained by the intratracheal injection of suspensions of the ExoU-producing PA103 P. aeruginosa strain or of its isogenic mutant PA103 exoU, defective in the toxin synthesis, ExoU was shown to enhance the severity of the infection and to induce higher mice mortality rate as well as leukopenia, thrombocytosis, vascular hyperpermeability and plasma transudation, evidenced, respectively, by the higher protein concentration in the bronchoalveolar lavage fluids (BALF) and accumulation of Evans blue dye, previously intravenous infectioned, in mice renal parenchyma. ExoU also favored platelet activation, evidenced by the higher concentration of platelets expressing P-selectin on their surface, greater number of platelet-derived microparticles and increased plasma concentration of thromboxane A2. Histopathology of the lungs and kidneys of PA103 - infected animals confirmed the formation of microthrombi, which were not detected in controls or in animals infected with the bacterial mutant. In lungs, ExoU induced an intense inflammatory response with high concentrations of total and polymorphonuclear leukocytes, interleukin-6 and tumor necrosis factor-alfa in mice BALF. Immunohistochemical analysis showed intense fibrin deposition in the alveoli...

Expressions of nitric oxide and plasminogen activator inhibitor type-1 in rabbit models of atherosclerosis and interference effect of atorvastatin / 吉林大学学报(医学版)

0.05).The levels of serum TC in groups A,B,and C were (23.51?10.58),(14.27?3.51)and(1.36?0.33)mmol?L-1, respectively; the levels of serum LDL in groups A,B,and C were (21.39?10.00),(14.23?4.01)and(0.72?0.35)mmol?L-1;there were significant differences between three groups (P0.05).Conclusion High-fat diet has no significant effect on the expressions of NO and PAI-1 in atherosclerosis rabbits .Atorvastatin can increase the expression of NO and decrease the expression of PAI-1,and can inhibit the progression of atherosclerosis.

Study on the Relationship of Plasminogen Activator Inhibitor type 1 and Ultrasensitive C-reative Protein in Patient with Metabolic Syndrome and Coronary Heart Disease / 医学研究杂志

Objective To investigate the relationship of plasminogen activator inhibitor type 1(PAI-1) and ultrasensitive C-reative protein(hsCRP) in patient with metabolic syndrome and coronary heart disease.Methods Between June 2006 and December 2007,87 patients with metabolic syndrome were divded into two groups:simple MS group which consisted of 45 patients and MS with CHD group which consisted of 42 patients.30 health people at the same stage,whose age and sex were similar with those in MS group served as normal control group.The levels of body mass index(BMI),waist circumference(WC),systolic blood presser(SBP),diastolic blood presser(DBP),triglyceride(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),fasting plasma glucose(FPG),PAI-1 and hsCRP were measared.Results BMI,WC,FPG,SBP,DBP,TG,PAI-1 and hsCRP in both MS groups were higher than those in normal control group(P

Adenoid Cystic Carcinoma : Participation of Urokinase-type Plasminogen Activator (uPA) and its Receptor (uPAR) in Tumor Invasion / Oral Science International

Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. <i>In vivo</i> and <i>in vitro</i>, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α₂ integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α₂ integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.

Adenoid Cystic Carcinoma: Participation of Urokinase-type Plasminogen Activator (uPA) and its Receptor (uPAR) in Tumor Invasion / Oral Science International

Adenoid cystic carcinoma (AdCC) is one of the most common malignant tumors of the salivary glands and has unique clinical features and behavior. AdCC grows slowly, but spreads relentlessly into adjacent tissues, with a proclivity for invading nerve and endothelial sheaths. Moreover, the frequency of recurrence and distant metastasis of AdCC is very high. <i>In vivo</i> and <i>in vitro</i>, AdCC produces a large amount of extracellular matrix (ECM), including basement membrane (BM) components, elastin, and mucopolysaccharides. The accumulation of ECM components in intercellular spaces results in the formation of a pseudocyst, which is the characteristic architecture of AdCC. AdCC cells degrade considerable amounts of mesenchymal-elaborated ECM through the urokinase-type plasminogen activator (uPA)-plasmin system. By contrast, tumor-produced ECM is resistant to degradation, because it contains plasminogen activator inhibitor type 1 (PAI-1). The migration response of AdCC cell lines to ECM, especially type I and type IV collagens, is much stronger than that of oral squamous cell carcinoma (SCC) cell lines, while both cell types generally show similar patterns of integrin subunit expression. The AdCC cell response to collagens is largely and exclusively inhibited by anti-α₂ integrin antibody. Surface uPA receptor (uPAR) expression by AdCC cell lines is greater than that by SCC cell lines and increases in response to collagen stimulation. This is accompanied by the assembly of numerous focal adhesions, consisting of the adapter proteins uPAR, α₂ integrin, vinculin, and paxillin. A role for uPAR in cell migration and assembly of adaptor proteins was also demonstrated by transfecting AdCC cells with an antisense uPAR RNA, which strongly reduced both responses. Therefore, the proclivity of AdCC cells to migrate to type I and IV collagens might be due to the overexpression of uPAR, which also plays a key role in focal adhesion assembly. In conclusion, the invasiveness of AdCC cells might be regulated by the interaction of uPA-uPAR with integrin.

Plasma Fibrinolysis Inhibitor Levels in Acute Stroke Patients with Thrombolysis Failure

BACKGROUND AND PURPOSE: Thrombolytics-induced recanalization fails in a significant portion of patients with ischemic stroke, which is partly due to the resistance of clots to lysis by thrombolytic agents. The pretreatment level of endogenous fibrinolysis inhibitors may affect such thrombolysis failure. METHODS: We studied 43 stroke patients whose arterial recanalization had been evaluated by angiography, and whose blood had been obtained prior to the administration of thrombolytic agents. Plasma samples from 34 healthy volunteers were used as normal controls. Plasminogen activator inhibitor type 1 (PAI-1) and thrombin-activatable fibrinolysis inhibitor (TAFI) levels were quantified using an enzyme-linked immunosorbent assay. RESULTS: Arteries were recanalized [Thrombolysis in Myocardial Infarction (TIMI) grade 2 or 3] in 30 patients, but not (TIMI grade 0 or 1) in the other 13. The plasma PAI-1 level was significantly higher in patients without recanalization (nonrecanalization) than in those with recanalization and in normal controls. The TAFI levels did not differ among the groups. CONCLUSIONS: The pretreatment PAI-1 levels are increased in acute stroke patients with thrombolysis failure.

Plasminogen Activator Inhibitor Type 1 Gene Polymorphism in Patients with Minimal Change Nephrotic Syndrome

PURPOSE: Hypercoagulability is present in patients with nephrotic syndrome. Plasminogen activator inhibitor type 1(PAI-1) is a major inhibitor of plasminogen activators. PAI-1 inactivates both tissue plasminogen activator(tPA) and urokinase plasminogen activator(uPA) by rapid formation of inactive 1:1 stoichiometric complexes. Recently some studies showed that the enhanced PAI-1 expression may be involved in the intraglomerular fibrinogen/fibrin- related antigen deposition seen in nephrotic syndrome. METHODS: PAI-1 gene promoter -844(G/A) polymorphism was evaluated in 146 children with minimal change nephrotic syndrome(MCNS) and 230 control subjects. The patients with MCNS were subdivided into 85 infrequent-relapser(IR) group and 61 frequent relapser(FR) group. PCR of PAI-1 gene promoter region including -844(G/A) and RFLP using the restriction enzyme Xho1 were performed for each DNA samples extracted from the groups. RESULTS: The distribution of PAI-1 genotype in the control group was G/G 81(32.5%), A/A 42(16.9%), and G/A 126(50.6%). The distribution of PAI-1 genotypes in the IR group of MCNS was G/G 29(34.1%), A/A 15(17.7%), and G/A 41(48.2%). The distribution of PAI-1 genotype in the FR group of MCNS was G/G 17(27.9%), A/A 18(29.5%), and G/A 26(42.6 %). There was a significantly increased frequency of A/A genotype(P=0.0251) in the FR group of MCNS. CONCLUSION: Our results indicate that the PAI-1 gene promoter A/A genotype may be associated with the FR in MCNS.

Effects of ginsenoside-Rg1 on levels of t-PA and PAI-1 / 中国药理学通报

Aim To explore the effects and its mechanisms of ginsenoside-Rg1 on level of t-PA and PAI-1.Methods Type 1 plasminogen activator inhibitor(PAI-1) and tissue type plasminogen activator(t-PA) activity in plasma were assayed using chromogenic substrate.Results The results showed that ginsenoside-Rg1 in vitro or in vivo significantly inhibited PAI-1activity,while increased t-PA activity.These effects were concentration-dependent.Intravenous Panax notoginsenoside Rg1 at 30,60,120 and 240 mg?kg~(-1) markedly suppressed PAI-1 level in plasma as well as platelet-released substances stimulated by thrombin,while increased plasma t-PA activity.And release level of PAI-1 owing to blood platelet was greatly decreased by ginsenoside-Rg1.Conclusion Ginsenoside-Rg1 showed potent antithrombosis due to the inhibition of PAI-1 and increase of t-PA.It might also be a advantagous mechanism to its antithrombsis.