Intervention effect of Tongxinluo capsule on renal fibrosis in diabetic nephropathy rats / 中国药房

OBJECTIVE To explore the intervention effect and related mechanism of Tongxinluo capsule on renal fibrosis in rats with diabetic nephropathy （DN）. METHODS Eight rats were selected as control group （ordinary feed）， the remaining rats were given high-glucose and high-fat diet combined with ip injection of streptozotocin （35 mg/kg） to induce DN model. Model rats were randomly divided into model group （purified water）， irbesartan group （positive control， 14.12 mg/kg） and Tongxinluo capsule group （0.3 g/kg）， including 12 rats in the model group and 11 rats for each of the other two groups. All groups were given relevant medicine or water intragastrically， once a day， for 16 consecutive weeks. After the last medication， fasting blood glucose and 24 h urinary total protein （24 h UTP） were detected. Pathological changes in renal cortex of rats in each group were observed. Serum levels of tissue-type plasminogen activator （PA） and plasminogen activator inhibitor 1 （PAI-1） were measured. mRNA expressions of transforming growth factor-β（1 TGF-β1）， type Ⅳ collagen（COL-Ⅳ）， Wnt4 and β-catenin in renal cortex of rats were detected. The protein depositions or expressions of TGF-β1， COL-Ⅳ， focal adhesion kinase （FAK）， integrin-linked kinase （ILK）， E-cadherin， PA， PAI-1， Wnt4 and β-catenin in renal cortex of rats were observed or determined. RESULTS Compared with model group， 24 h UTP of rats in Tongxinluo capsule group were all significantly reduced （P＜0.05）； pathological damage and fibrosis of renal cortex were relieved； the expression of PA in serum and renal cortex was significantly increased， while PAI-1 level was significantly reduced （P＜0.05）； the depositions of COL-Ⅳ and TGF-β1 in renal cortex were all reduced， and corresponding mRNA expression was decreased significantly （P＜0.05）； the depositions of ILK and FAK were decreased， while the deposition of E-cadherin was increased； protein and mRNA expressions of Wnt4 and β-catenin were significantly reduced （P＜0.05）. CONCLUSIONS Tongxinluo capsule can relieve pathological damage to renal tissue and renal fibrosis of DN model rats， and reduce extracellular matrix deposition. The mechanism may be related to regulation of fibrinolytic system activity， the decrease of ILK and FAK expression， and inhibition of Wnt/β-catenin signaling pathway.

Epidermal growth factor receptor regulates fibrinolytic pathway elements in cervical cancer: functional and prognostic implications

Epidermal growth factor receptor (EGFR) signaling and components of the fibrinolytic system, including urokinase-type plasminogen activator (uPA) and thrombomodulin (TM), have been implicated in tumor progression. In the present study, we employed cBioPortal platform (http://www.cbioportal.org/), cancer cell lines, and an in vivo model of immunocompromised mice to evaluate a possible cooperation between EGFR signaling, uPA, and TM expression/function in the context of cervical cancer. cBioPortal analysis revealed that EGFR, uPA, and TM are positively correlated in tumor samples of cervical cancer patients, showing a negative prognostic impact. Aggressive human cervical cancer cells (CASKI) presented higher gene expression levels of EGFR, uPA, and TM compared to its less aggressive counterpart (C-33A cells). EGFR induces uPA expression in CASKI cells through both PI3K-Akt and MEK1/2-ERK1/2 downstream effectors, whereas TM expression induced by EGFR was dependent on PI3K/Akt signaling alone. uPA induced cell-morphology modifications and cell migration in an EGFR-dependent and -independent manner, respectively. Finally, treatment with cetuximab reduced in vivo CASKI xenografted-tumor growth in nude mice, and decreased intratumoral uPA expression, while TM expression was unaltered. In conclusion, we showed that EGFR signaling regulated expression of the fibrinolytic system component uPA in both in vitro and in vivo settings, while uPA also participated in cell-morphology modifications and migration in a human cervical cancer model.

Alteration of heat shock protein 20 expression in preeclamptic patients and its effect in vascular and coagulation function / 医学前沿

Preeclampsia (PE) is a pregnancy-specific, multi-system disorder and the leading cause of maternal and perinatal morbidity and mortality in obstetrics worldwide. Excessive vasoconstriction and dysregulated coagulation function are closely associated with PE. Heat shock protein 20 (HSP20) is ubiquitously expressed under normal physiological conditions and has important roles in vascular dilatation and suppression of platelet aggregation. However, the role of HSP20 in the pathogenesis of PE remains unclear. In this study, we collected chorionic plate resistance arteries (CPAs) and serum from 118 healthy pregnant women and 80 women with PE and detected the levels of HSP20 and its phosphorylated form. Both HSP20 and phosphorylated HSP20 were downregulated in CPAs from women with PE. Comparison of the vasodilative ability of CPAs from the two groups showed impaired relaxation responses to acetyl choline in preeclamptic vessels. In addition to the reduced HSP20 in serum from women with PE, the platelet distribution width and mean platelet volume were also decreased, and the activated partial thromboplastin time and thromboplastin time were elevated.With regard to the vital roles of HSP20 in mediating vasorelaxation and coagulation function, the decreased HSP20 might contribute to the pathogenesis of PE.

Effects of Salvia Miltiorrhiza and Rrhizoma Alismatis on Lipid Metabolism and Fibrinolytic System in Rats with Non-alcoholic Fatty Liver / 中国药师

Objective:To preliminarily discuss the mechanism of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of lipid metabolism through regulating the imbalance of fibrinolytic system in rats with non-alcoholic fatty liver. Methods:The model of non-alcoholic fatty liver in rats was duplicated by high-fat diet feeding. Totally 60 adult Wistar rats were randomly divided into 6 groups (n=10 per group), namely the control group, the model group, Salvia miltiorrhiza group, Rrhizoma alismatis group, Salvia miltiorrhiza and Rrhizoma alismatis group,and Dongbaogantai group. The control group and the model group were given distilled water,and the other group was given Salvia miltiorrhiza,Rrhizoma alismatis,Salvia miltiorrhiza combined with Rrhizoma alismatis and Dongbaogantai,respectively. Rhizoma Alismatis decoction at high dose and low dose as well as Dongbaogantai was respectively adminis-trated in the designed groups,and the corresponding indices were detected 4 weeks later. Results:In the model control group,the con-tents of TC、TG、FFA in serum and the expression of PAI-1 were significantly elevated(P<0.05 or P<0.01),while the expression of t-PA was significantly reduced(P<0.01).After treatment,the contents of TC、TG、FFA in serum and the expression of PAI-1 in every treatment groups were reduced(P<0.01),while the expression of t-PA was elevated(P<0.01).Conclusion: Increasing the expres-sion of t-PA and reducing the expression of PAI-1 might be viewed as the mechanisms of Salvia miltiorrhiza and Rrhizoma alismatis in the prevention and treatment of non-alcoholic fatty liver disease.

Mechanism study of hypercoagulative state based on cytokines-NF-kappa B signaling pathway in Sjogren′s syndrome patients / 中国免疫学杂志

Objective:To observe the changes in coagulation parameters, peripheral blood cytokines, NF-kappa B signaling pathway protein, laboratory indexes in Sjogren′s syndrome ( SS ) patients, thus to explore the mechanism of hypercoagulable state. Methods:60 patients with SS and 20 healthy persons were randomly selected as the study group and the control group;Automatic coagulation analyzer was used to detect the value of coagulation parameters [ activated partial thromboplastin time ( APTT) ,prothrombin time ( PT) , plasma fibrinogen ( FIB ) , prothrombin time ( TT ) , D-dimer ( DD ) ]; ELISA method was performed to observe the expression of related cytokines(IL-1β,TNF-α,IL-10) and NF-κB signaling pathway proteins (p65,p50,IκBα); Westergren method was used to determine erythrocyte sedimentation rate ( ESR) ,and automatic biochemical analyzer to examine immune protein( IgG,IgA, IgM,GLO) and high sensitivity C-reactive protein (hs-CRP). Results: Blood coagulation parameters in 60 patients with SS were at least one abnormal for 46 cases,accounting for 76. 7% of the subjects. Among them,the abnormal rate of D-D was the highest,followed by FIB,APTT,PT,TT. Compared with the control group,D-D,FIB were significantly increased in SS patients,and TT,PT,APTT was not found obviously different. In addition,IL-1β,TNF-α,P50,P65,IκBα and inflammatory indexes like ESR,hs-CRP,IGg,GLO,ESSDAI, corneal staining score increased while the salivary flow rate,tear film break-up time and IL-10 decreased significantly( P<0. 05 or P<0. 01). Correlation analysis showed that the coagulation parameters FIB were positively correlated with the salivary flow rate,TNF-α, P50,P65,ESR,hs-CRP,while negatively correlated with IL-10,that TT was negatively correlated with TNF-α;that D-D was positively correlated with TNF-α, IL-1β, P65, ESR, hs-CRP, ESSDAI and corneal staining score, while negatively correlated with IL-10. Conclusion: SS patients generally have hypercoagulable state, and may be associated with the imbalance of cytokines, abnormal activation NF-kappa B signaling pathway,which mediates vascular endothelial cell damage,causing coagulation/fibrinolytic system dis-orders.

Effect of fibrinolytic system on the podocyte injury in rats with membranous nephropathy / 中国实验动物学报

Objective To observe the expression of uPA, tPA and PAI-1 in whole blood of rat membranous ne-phropathy ( MN) models induced by cationic bovine serum albumin ( C-BSA) , and to explore the effect of fibrinolytic sys-tem on podocyte apoptosis and pathological changes. To explore the possible preventive and therapeutic effects and the pos-sible mechanisms of early prevention of fibrinolysis. Methods We developed a MN model with the modified Border meth-od. At the end of the 1st, 2nd, 3th, and 4th week of immunization, respectively, the levels of whole blood uPA, tPA and PAI-1 were determined by ELISA. The rat kidney tissues were examined by light microscopy and electron microscopy to i-dentify the pathological changes. The expression levels of nephrin and WTl were detected with immumofluorescence staining and their correlation was analyzed. Results Compared the treatment group with control group, the levels of whole blood uPA, tPA and PAI-1 of the model group were decreased, while PAI-1 was elevated, showing a significant difference ( P<0. 05). The degree of renal interstitial fibrosis was more serious. Correlation analysis showed that the whole blood tPA and uPA levels were positively correlated with the changes of nephrin protein expression in the kidney tissue, while the whole blood PAI-1 level was negatively correlated with the nephrin protein expression in the kidney tissue. Conclusions In the process of MN development, the fibrinolytic system may have important significance for podocyte apoptosis. Determination of early phase of MN podocyte injury may be another therapy target for prevention of the disease development, and then pro-vide new ideas for clinical research and drug development for MN.

The Fibrinolytic Efficacy and Impact on Plasma von Willlebrand Factor of Losartan Compared with Atenolol in Essential Hypertensives / 中华高血压杂志

Objectives To compare the effects of losartan and atenolol on fibrinolytic system and plasma von willebrand factor (vWF) in patients with essential hypertension. Methods Sixty patients with mild to moderate essential hypertension were randomized to receive lostartan(50 mg/d, n=30) or atenolol(50 mg/d, n=30) for 8 weeks. If the goal blood pressure(

A Study on the Changes of Protein C and Fibrinolytic System in Patients with Cerebrovasculer Disease and Intervened Treatment / 医学研究杂志

Objective To investigate the changes of protein C and fibrinolytic system in patients with acute cerebrovasculer disease and the influence of intervened treatments on acute cerebral infarction(ACI).Methods Determinations of protein C(PC),protein S (PS),thrombomodulin(TM),Tissue-type plasminogen activater(t-PA),plasminogen activator inhabitor(PAI) were performed in patiens with acute cerebrovasculer disease and normal control(NC),then redeterminated these items after treatments in patients with ACI.Results PC,PS:The levels in patients with ACI were significantly lower than that in other groups.After dreatments,the levels in patients with ACI increased.There were no significantly discrepancy in acute cerebral hemorrhage(ACH) and lacunar cerebral infarct(LCI) compared with NC;TM:The levels in patients with ACH,ACI were significantly higher than that with LCI and NC.After dreatments,the levels in patients with ACI decreased;t-PA:The levels in patients with ACI were lower than NC,whereas the levels in patients with ACH increased.After dreatments,the levels in patients with ACI increased;PAI:The levels in patients with ACI were significantly higher than NC,and also found that the levels in patients with ACH and LCH were higher compared with NC.The levels in patients with ACI decreased after dreatments.Conclusions There are obviously abnormalities in plasma coagulative and fibrinlytic parameters in acute cerebrovasculer disease;To check the levels of PC,PS,TM,t-PA,PAI are important to predict the type of stroke,the seriousness of disease,the effect of treatment,prognosis of the cases and suggest that earlier treatments be important.

Correlativity between blood-stasis syndrome in cardiopathy and activity of f ibrinolytic system / 中华中医药杂志

Objective:To explore the pathologic mechanism of blood-stasis syndrome in cardiopathy(BSSC) and its different syndrome types from the activity of fi brinolytic system.Methods:72 cases with BSSC,20 cases with non-blood-stasis syndrome in cardiopathy(NBSSC) were observed at random,20 healthy cases as control.The levels of tissue-plasminogen activator(t-PA) and plasminogen activator inhibitor-1(PAI-1) in blood plasma were detected by ELISA.Results:①The level of t-PA in the group of BSSC was signifi cantly lower than that in the groups of healthy control and NBSSC(P

Studies on Fibrinolytic System Behavior in Women with Polycystic Ovary Syndrome / 대한산부인과학회잡지

OBJECTIVE: To evaluate the plasma concentration of plasminogen activator inhibitor 1, main regulator of fibrinolytic system in women with polycystic ovary syndrome and to clarify whether it may be involved in the pathogenesis of chronic anovulation. METHODS: Fibrinolytic system (plasma fibrinogen, plasminogen, plasminogen activator inhibitor 1 concentration) was assayed in women with polycystic ovary syndrome and compared to normal controls. RESULTS: Women with polycystic ovary syndrome had significantly higher plasminogen activator inhibitor 1 and fibrinogen concentration compared to normal controls. CONCLUSION: Women with polycystic ovary syndrome may have an imbalance in the fibrinolytic system that is tilted towards a reduced production of the proteolytic enzyme plasmin. It may result in impaired follicular rupture and anovulation at cellular level in the ovaries.